Anxiety Disorder

Current Clinical Psychiatry
Series Editor: Jerrold F. Rosenbaum
Roma A. Vasa
Amy Krain Roy Editors
Pediatric Anxiety
Disorders
A Clinical Guide
Current Clinical Psychiatry
Series Editor
Jerrold F. Rosenbaum, MD
For further volumes:

http://www.springer.com/series/7634
Roma A. Vasa • Amy Krain Roy
Editors
Pediatric Anxiety Disorders

A Clinical Guide
Editors
Roma A. Vasa Amy Krain Roy
Director of Education and Training Fordham University
Kennedy Krieger Institute Bronx, NY, USA
Baltimore, MD, USA
ISBN 978-1-4614-6598-0 ISBN 978-1-4614-6599-7 (eBook)

DOI 10.1007/978-1-4614-6599-7
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Preface
Over the past decade, significant advances in research methodology have stimulated dramatic prog-
ress in the field of child psychiatry in general and pediatric anxiety disorders, more specifically.
Advances in neuroimaging, developmental and affective neuroscience, and genetics have provided
a solid foundation for the development of novel etiological models that are now being tested. Further,
the publication of several rigorous multisite trials of pharmacological and psychotherapeutic inter-
ventions has substantially improved our knowledge of the most effective methods to treat pediatric
anxiety disorders. The Diagnostic and Statistical Manual of Mental Disorders is currently under its
sixth revision, with changes driven by these empirical findings, including the integration of dimen-
sional assessment approaches, which has not been done before. Thus, this volume, Pediatric Anxiety
Disorders: A Clinical Guide, is being published at an exciting time in the field of psychiatry. The aim
of this text is to bridge the most up-to-date research findings with relevant clinical perspectives mak-
ing it a unique and essential resource to established clinicians and researchers, as well as students
and trainees.
This book is organized into four sections, each of which includes chapters on a specific area of
interest. The first section reviews the current research regarding etiological mechanisms of pediatric
anxiety. It begins with a comprehensive overview of the animal literature showing cross-species
homology in the neural mechanisms underlying fear processing, which has been essential to delineat-
ing the pathophysiology of anxiety disorders and, more recently, has provided the foundation for
novel treatment approaches. The next chapter illustrates how advances in neuroimaging techniques
have allowed translation of basic animal fear models to humans, including children and adolescents,
with anxiety disorders. The final chapter of this section focuses on temperamental risk factors for
pediatric anxiety disorders, an area that has grown significantly in recent years due to unique longitu-
dinal work.
The second section provides in-depth descriptions of the anxiety disorders that affect children and
adolescents. Each chapter includes descriptions of any proposed changes for DSM5, as well as the
most current research findings regarding etiology, assessment, and treatment. Clinical case scenarios
provide real-world examples of presenting concerns and putative responses to treatment.
The third section summarizes the literature on empirically supported assessment tools and evi-
dence-based cognitive-behavioral and pharmacological interventions for pediatric anxiety disorders.
The authors of these chapters have included comprehensive summary tables that can serve as quick
reference tools.
The final section of the text is dedicated to understanding how anxiety manifests in two special
populations, children with chronic medical illnesses and those with autism spectrum disorders. The
authors of these chapters explore how anxiety is conceptualized in the context of these primary disor-
ders and discuss special considerations for assessment and treatment.
v
vi Preface
The editors are fortunate to have leading authorities in pediatric anxiety from the fields of cogni-
tive neuroscience, cognitive-behavioral practice, and pharmacology to author the chapters of this
book. We are grateful to them for all of their time and efforts. We also wish to thank Fawad Viqar,
Rachel Chizkov, Rachael Tillman, and Laura Carroll for their assistance with the editing process.
Finally, we wish to thank our editor, Barbara Lopez-Lucio, at Springer for her dedicated guidance
and editorial expertise.
Baltimore, MD, USA Roma A. Vasa

Bronx, NY, USA Amy Krain Roy
Contents
Part I Neurobiology and Temperament
Fear Models in Animals and Humans ....................................................................................... 3

Catherine A. Hartley and Elizabeth A. Phelps
Neurobiology of Pediatric Anxiety Disorders ........................................................................... 23
Amanda E. Guyer, Carrie L. Masten, and Daniel S. Pine
Temperamental Risk Factors for Pediatric Anxiety Disorders............................................... 47
Kristin A. Buss and Elizabeth J. Kiel
Part II Anxiety Disorders
Generalized Anxiety Disorder in Children and Adolescents ................................................... 71

Golda S. Ginsburg and Nicholas W. Affrunti
Pediatric Social Phobia ............................................................................................................... 91
Vasco M. Lopes and Anne Marie Albano
Specific Phobias ........................................................................................................................... 113
Thomas H. Ollendick, Maria J.W. Cowart, and Ella L. Milliner
Separation Anxiety Disorder...................................................................................................... 129
Aleta G. Angelosante, Magdalena A. Ostrowski, and Rachel R. Chizkov
Panic Disorder ............................................................................................................................. 143
Aleta G. Angelosante and Magdalena A. Ostrowski
Obsessive-Compulsive Disorder in Children and Adolescents ............................................... 157
Adam B. Lewin, Jennifer M. Park, and Eric A. Storch
Posttraumatic Stress Disorder in Children and Adolescents .................................................. 177
Damion J. Grasso and Joan Kaufman
Selective Mutism ......................................................................................................................... 209
Courtney P. Keeton
vii
viii Contents
Part III Assessment and Treatment
Assessment of Anxiety Disorders: Categorical and Dimensional Perspectives ..................... 231

Yasmin Rey, Carla E. Marin, and Wendy K. Silverman
Cognitive–Behavioral Treatment for Pediatric Anxiety Disorders ........................................ 269
Kendra L. Read, Connor M. Puleo, Chiaying Wei, Colleen M. Cummings,
and Philip C. Kendall
Psychopharmacology of Pediatric Anxiety Disorders ............................................................. 289
Justin W. Mohatt, Alex Eve Keller, and John T. Walkup
Part IV Special Topics
Anxiety in Children with Chronic Medical Illness .................................................................. 317

Patrick M. Kelly and Emily J. Frosch
Anxiety in Children with Autism Spectrum Disorder ............................................................. 345
Heather Jennett, Roma A. Vasa, and Louis Hagopian
Index ............................................................................................................................................. 379

Contributors
Nicholas W. Affrunti Department of Psychological and Brain Sciences, University of Louisville,

Louisville, KY, USA
Anne Marie Albano Department of Psychiatry, Columbia University Clinic for Anxiety and Related
Disorders, Columbia University, New York, NY, USA
Aleta G. Angelosante NYU Langone Medical Center, New York, NY, USA
Kristin A. Buss Department of Psychology, The Pennsylvania State University, University Park,
PA, USA
Rachel R. Chizkov Department of Child and Adolescent Psychiatry, NYU Langone Medical Center,
New York, NY, USA
Maria J.W. Cowart Virginia Tech, Child Study Center, Blacksburg, VA, USA
Colleen M. Cummings Department of Psychology, Temple University, Philadelphia, PA, USA
Emily J. Frosch Division of Child and Adolescent Psychiatry, Department of Psychiatry and
Behavioral Science, The Johns Hopkins University School of Medicine, Baltimore, MD, USA
Golda S. Ginsburg Division of Child and Adolescent Psychiatry, The Johns Hopkins University
School of Medicine, Baltimore, MD, USA
Damion J. Grasso University of Connecticut Health Center, Farmington, CT, USA
Amanda E. Guyer Department of Human Ecology and Center for Mind and Brain, University of
California, Davis, CA, USA
Louis Hagopian Neurobehavioral Unit, Department of Behavioral Psychology, Kennedy Krieger
Institute, Baltimore, MD, USA
Catherine A. Hartley Department of Psychology, New York University, New York, NY, USA
Heather Jennett Director of Clinical Services, Little Leaves Behavioral Services, Washington, DC,
USA
Joan Kaufman Yale University School of Medicine, New Haven, CT, USA
Courtney P. Keeton Department of Psychiatry and Behavioral Sciences, Johns Hopkins Medical
Institution, Baltimore, MD, USA
ix
x Contributors
Alex Eve Keller Department of Child and Adolescent Psychiatry, Weill Cornell Medical College,
New York, NY, USA
Patrick M. Kelly Division of Child and Adolescent Psychiatry, Department of Psychiatry and
Behavioral Sciences, The Johns Hopkins Hospital, Baltimore, MD, USA
Philip C. Kendall Department of Psychology, Temple University, Philadelphia, PA, USA
Elizabeth J. Kiel Psychology Department, Miami University, Oxford, OH, USA
Adam B. Lewin Neuropsychiatry – University of South Florida, St. Petersburg, FL, USA
Vasco M. Lopes Department of Psychology, Fordham University, Bronx, NY, USA
Carla E. Marin Florida International University, Miami, FL, USA
Carrie L. Masten Department of Psychology and Human Development, Peabody College, Vanderbilt
University, Nashville, TN, USA
Ella L. Milliner Griffith University, Gold Coast, QLD, Australia
Justin W. Mohatt Child Division, Department of Psychiatry, Weill Cornell Medical College,
New York, NY, USA
Thomas H. Ollendick Virginia Tech, Child Study Center, Blacksburg, VA, USA
Magdalena A. Ostrowski Kean University, North Avenue, Hillside, NJ, USA
Jennifer M. Park Department of Psychology, University of South Florida, Tampa, FL, USA
Elizabeth A. Phelps Nathan S. Kline Institute for Psychiatric Research, Departments of Psychology
and Neural Science, New York University, New York, NY, USA
Daniel S. Pine Section on Development and Affective Neuroscience, National Institute of Mental
Health, Bethesda, MD, USA
Connor M. Puleo Department of Psychology, Temple University, Philadelphia, PA, USA
Kendra L. Read Department of Psychology, Temple University, Philadelphia, PA, USA
Yasmin Rey Florida International University, Miami, FL, USA
Wendy K. Silverman Department of Psychology, Florida International University, Miami,
FL, USA
Eric A. Storch University of South Florida, St. Petersburg, FL, USA
Roma A. Vasa Division of Child and Adolescent Psychiatry, Education and Training, Kennedy
Krieger Institute, Baltimore, MD, USA
John T. Walkup Child Division, Department of Psychiatry, Weill Cornell Medical College,
New York, NY, USA
Chiaying Wei Department of Psychology, Temple University, Philadelphia, PA, USA
Part I
Neurobiology and Temperament
Fear Models in Animals and Humans
Catherine A. Hartley and Elizabeth A. Phelps
Abstract While fear learning is an adaptive behavior critical to our survival, excessive fear can markedly
impair one’s ability to function and is a central characteristic of anxiety disorders. In this chapter, we
review research detailing the neurobiological mechanisms underpinning fear learning and regulation.
We draw on research in both animal models and humans, highlighting developmental research when-
ever possible. In the first section we review the brain systems that support fear acquisition through
both direct experience and social learning. In the second section, we focus on the various means by
which learned fears can be lessened, including extinction, cognitive regulation strategies, actively
coping with fear, and persistently inhibiting fear through reconsolidation. This basic fear-learning
model provides a neuroscientific framework for understanding the role of Pavlovian fear learning in
anxiety disorders and suggests potential approaches for treatment.
Keywords Fear • Conditioning • Extinction • Emotion regulation • Anxiety
The ability to recognize and respond to potential sources of harm in the environment is critical for
survival. The state of fear that results from the detection of proximal threat serves many important
functions. Fear facilitates information gathering through heightened vigilance, enables rapid reac-
tions, and gates learning to promote the long-term retention of salient information. While fear plays a
central role in promoting adaptive behavior, excessive fear can markedly impair one’s ability to func-
tion and is a central characteristic of anxiety disorders. Detailed research examining fear learning in
animal models and humans has generated a detailed neuroscientific understanding of how fear
responses are acquired. More recent research has begun to elucidate the various methods by which
learned fears can be modified or controlled.
This research provides a framework for understanding the neural systems underlying anxiety dis-
orders and may yield novel insights into possible treatments. Of note, the majority of both human and
animal studies have examined the acquisition and control of fear in adults, with few examinations of
how these learning and regulatory processes might differ in childhood or adolescence. Thus, the bulk
of this review will focus on adult studies with reference to pediatric research whenever possible.
C.A. Hartley
Department of Psychology, New York University, New York, NY, USA
e-mail: cate@nyu.edu
E.A. Phelps (*)
Nathan S. Kline Institute for Psychiatric Research, Departments of Psychology and Neural Science,
New York University, New York, NY, USA
e-mail: liz.phelps@nyu.edu
R.A. Vasa and A.K. Roy (eds.), Pediatric Anxiety Disorders: A Clinical Guide, Current Clinical Psychiatry, 3
DOI 10.1007/978-1-4614-6599-7_1, © Springer Science+Business Media New York 2013
4 C.A. Hartley and E.A. Phelps
In this chapter, we review research detailing how fear responses are learned and regulated. In the
real world, objects, sounds, or places that are associated with previous traumatic events in our lives
can come to elicit fear responses. In addition, humans can readily acquire fears through social means
of transmission, such as through verbal instruction or observation of another person’s negative experi-
ences. Experimental studies examining Pavlovian cued conditioning, contextual conditioning, and
social learning of fear have shed light on the neural mechanisms supporting such fear associations. In
the first part of this chapter we review the brain systems linked to fear acquisition. The latter sections
of this review focus on the range of techniques by which fears can be lessened, including simple
exposure in extinction training, cognitive strategies to regulate fear, developing means to actively
cope with fear, and persistently inhibiting the fear by targeting memory reconsolidation.
Fear Acquisition
Below we review experiential and social means by which novel fears may be acquired. Pavlovian cued
conditioning and contextual conditioning, respectively, model the processes by which negative affec-
tive value may be assigned to a stimulus or context. Fears may also be acquired through observation
or explicit instruction. Here we describe each of these means of fear learning and review their neural
substrates.
Pavlovian Cued Conditioning
Pavlovian fear conditioning provides an experimental model for the process by which neutral stimuli
in the world acquire negative affective value [1]. In a typical Pavlovian fear conditioning paradigm, a
neutral stimulus, such as a tone, is paired with an intrinsically aversive unconditioned stimulus (US),
such as a shock. The shock elicits a range of unconditioned autonomic, endocrine, and behavioral
responses, including freezing in rodents, and increases in skin conductance in humans. After one or
more pairings, the previously neutral stimulus, now a conditioned stimulus (CS), acquires the capacity
to elicit these fear responses, or conditioned responses (CRs).
Extensive research in animal models has delineated the neural circuits that support Pavlovian fear
conditioning (see [2, 3]; Fig. 1). This work highlights the necessary role of the amygdala in acquisi-
tion, storage, and expression of fear learning. The amygdala is a heterogenous structure composed of
several subnuclei that play distinct roles in fear learning. The lateral nucleus of the amygdala (LA)
receives convergent thalamic and cortical projections signaling the presence of the CS and US [4–7].
Pairing of the two stimuli gives rise to synaptic plasticity within the LA [8, 9]. When the CS is then
presented alone, the LA activates the central nucleus of the amygdala (CE) [10], which controls the
expression of the fear response via projections to brainstem and hypothalamic regions [11]. Distinct
cells within the LA maintain the long-term representation of this fear memory [12] and remain respon-
sive to the presentation of a CS even when the behavioral fear response is not expressed. This persis-
tent encoding of the fear association may support the commonly observed return of fears that have
been previously diminished through extinction learning [13].
Although studies of fear acquisition have focused primarily on the role of the amygdala, recent
evidence in animal models suggests that the prelimbic medial prefrontal cortex is necessary for the
expression of learned fear (Fig. 1). Lesions of the prelimbic cortex do not prevent initial fear acquisi-
tion or expression [14, 15]; however, pharmacological inactivation of the prelimbic cortex following
conditioning disrupts fear expression [16] while prelimbic stimulation increases fear expression [17].
Neurons in prelimbic cortex exhibit sustained responses to CS presentation that parallel the duration
Fear Models in Animals and Humans 5
Fig. 1 Neurocircuitry supporting fear acquisition. The lateral nucleus (LA) of the amygdala receives afferent sensory
input regarding experienced, observed, or instructed information about the CS–US relationship and is the site of plastic-
ity representing the fear memory during conditioning. The LA and BA are interconnected and both project to the central
nucleus (CE), which has outputs to brainstem and hypothalamic regions that control the expression of the CR. Following
conditioning, the prelimbic (PL) region of the ventromedial prefrontal cortex (vmPFC) is activated via the BA following
CS presentations and drives the expression of conditioned fear. Projections from the hippocampus to the basal nucleus
(B) of the amygdala process contextual information during conditioning and may gate fear expression through the CE
of the behavioral freezing response [18], suggesting that the prelimbic cortex drives the expression of
conditioned fear. The prelimbic cortex receives inputs from the LA [19] and projects to the basal
nucleus of the amygdala (BA), which in turn projects to the CE. Following CS presentation, the pre-
limbic cortex might transform phasic signals from the LA into sustained prelimbic firing that directly
influences fear expression via its CE projections.
Discrimination conditioning paradigms are often used in human fear research. In these paradigms,
two conditioned stimuli are presented. These may be auditory tones or more typically, neutral visual
stimuli such as colored shapes. Some studies use visual stimuli as CSs that are capable of eliciting fear
responses even prior to conditioning (e.g., images of snakes, spider, or fearful faces). These so-called
“prepared” stimuli may elicit more robust physiological responses and more persistent conditioned
associations [20]. In a discrimination paradigm, one stimulus, the CS+, is paired with a US on a subset
of the trials, while the other, the CS− is never paired with shock. Measurable correlates of sympathetic
nervous system activity, such as skin conductance responses or pupil dilation, are recorded and
assessed for each stimulus. The difference in responding to the threat stimulus (CS+) versus the safety
signal (CS−) serves as a measure of the discriminative CR that is assumed to reflect one’s degree of
threat-specific fear expression.
Studies in humans suggest that the neurocircuitry underlying Pavlovian fear conditioning is
conserved across species (see [21] for a review). Both human lesion and neuroimaging studies support
the central role of the amygdala in fear conditioning. Patients with both unilateral and bilateral lesions
of the amygdala fail to display a conditioned skin conductance response to a reinforced CS [22, 23].
Functional magnetic resonance imaging studies (fMRI) of Pavlovian fear conditioning observed
increased blood oxygen level-dependent (BOLD) signal in the amygdala to a conditioned stimulus
versus a neutral stimulus [24–27].
In addition to the engagement of the amygdala, fMRI studies of fear conditioning commonly
report increases in BOLD activation in the dorsal anterior cingulate cortex (dACC) in response to
CS presentation. Both cortical thickness in this region and CS-evoked BOLD activation correlated
positively with the magnitude of conditioned fear expression [28], suggesting that the dACC may
mediate fear expression in humans. While homology across species is difficult to ascertain, the
authors of this study propose that the dACC may play a similar role in fear expression to the rodent
prelimbic region.
Studies in humans examining differences in fear conditioning across development suggest that dis-
crimination between threat and safety stimuli improves with age [29, 30]. An fMRI study examining age
effects on discriminative fear conditioning reported that the increased differentiation of the CS+ versus
CS− in adults versus adolescents correlated with their recruitment of dlPFC regions during fear condi-
tioning [30]. While not typically proposed to play a key role in fear learning, the authors suggest that the
dorsolateral prefrontal cortex (dlPFC) activity in this task may reflect a more general stimulus classification
function. In contrast, adolescents showed significant differential activity (CS+ > CS−) in the amygdala
and hippocampus, while adults did not. Another study comparing discriminative fear learning in healthy
versus anxious adolescents found that while both groups showed comparable degrees of discrimination,
anxious adolescents displayed higher fear ratings overall, independent of stimulus type [31].
Collectively, convergent evidence in both animal models and humans suggests that the amygdala is
necessary for the acquisition, storage, and expression of cued Pavlovian conditioned fear. Furthermore,
in both species, prefrontal cortical regions appear to modulate conditioned fear expression.
Contextual Conditioning
While the amygdala is critical for fear learning to specific cues, in many circumstances the learned
fear response extends to the larger context in which the aversive event occurred. This contextual fear
is adaptive in that the location and circumstances under which dangerous events occur can be as infor-
mative about the impending danger as a specific cue that immediately precedes the event. In addition,
the same cue may be dangerous in one context (e.g., a gun on a battleground) and safe in another
context (e.g., a gun at a sporting store). Context allows one to adaptively modulate the cued-fear
response, so it is appropriate to the situation. However, context can comprise many aspects of the
environment, and how one interprets the context can be flexible. At times fear of context can generalize
excessively, resulting in disorders such as phobias (particularly agoraphobia).
The contextual fear response requires the involvement of the hippocampus (Fig. 1), which is impor-
tant in encoding contextual aspects of memory more broadly [32]. In rodents, conditioned fear to the
context is assessed by placing the animal in a novel cage or context prior to the Pavlovian conditioning
protocol and the presentation of the CS–US pairing. After fear conditioning, the animal exhibits not
only a conditioned fear response to the CS but also the context in which the conditioning occurred.
If amygdala damage follows, the animal fails to show conditioned fear to both the cue and context;
however, if damage is localized to the hippocampus, conditioned fear to the CS is intact, but the ani-
mal no longer exhibits fear to the context [33]. Interestingly, unlike amygdala lesions, which impair
conditioned fear even if damage occurs long after fear conditioning, the impact of hippocampal dam-
age on contextual fear expression diminishes with the amount of time that passes following condition-
ing. This temporal gradient of retrograde amnesia for contextual fear following hippocampal damage
suggests that once the contextual fear memory is fully consolidated, the hippocampus is no longer
needed for its expression.
Studies on the development of contextual fear conditioning in rodents suggest pronounced qualita-
tive differences in learning across the lifespan. Both pre-weanling (postnatal day 17, P17) and post-
weanling (P24) rats show intact tone shock conditioning; only post-weanling rats exhibited freezing
to the conditioning context on the subsequent day [34]. This contextual conditioning deficit is thought
to reflect the increased maturation of the hippocampus in the older animals. Furthermore, a recent
finding in mice suggests that the expression of contextual fear appears to be temporarily suppressed
during adolescence [35]. In this study, contextual fear memories learned during or prior to adoles-
cence were not expressed during this developmental stage; however, these memories reemerge during
adulthood. This temporary suppression of contextual fear expression is proposed to foster the exploratory
behavior necessary for the transition from maternal care into independence, which typically occurs
during this developmental stage.
In humans, finding independent conditioned fear effects for cue and context in the laboratory is
somewhat difficult. The experimental setting is itself a strong context, and the use of techniques like
brain imaging does not permit alterations of the actual context (i.e., the MRI machine). As a result,
most investigations in humans examine the impact of context on cued conditioned fear expression.
One such study, using images of two rooms as contexts and the colors of a light in the rooms as cues
(CS+ and CS−), demonstrated that cued fear learned in one context and extinguished in another shows
renewal upon reintroduction to the fear context [36]. However, there is evidence for enhanced fear to
the context in conditioning paradigms where there is no distinct predictive cue CS [37, 38], and neu-
roimaging studies assessing the effect of context independent of cue report enhanced activation of the
hippocampus [38, 39]. More recently, virtual reality techniques, similar to those that have been used
in exposure therapy treatments for phobias [40], have been used to examine contextual fear in humans
[38, 41]. Manipulating the context with virtual reality has enabled the independent assessment of cue
and contextual fear-learning effects in a single learning paradigm in humans [42], revealing that con-
textual fear is acquired more rapidly than cued fear and that conducting cued-fear extinction in the
acquisition context impedes extinction learning.
Social Learning of Fear
Although Pavlovian fear conditioning is a powerful model for understanding fear across species, it
requires direct experience with an aversive event. In humans, many of our fears are learned through
social means without direct aversive experience. For instance, a common phobia is fear of germs.
Although science tells us germs exist, our perceptual systems do not detect them. Nevertheless, by
learning about germs and their consequences through verbal instruction from parents and others, we
routinely take preventative steps to diminish their potentially harmful effects. For some, this symbolic
knowledge of the dangers of germs results in unwarranted fear and excessive preventative measures.
This is an example where learning fear through social communication can result in a robust fear
response and psychopathology.
In general, learning fears through social communication is adaptive in that one does not need to
have painful experiences to know about potential threats. Social fear learning also expands the range
of stimuli and events that can be associated with potential aversive outcomes. There are two primary
means of social fear learning. The first, verbal instruction, is dependent on language and is unique to
humans. The second is learning through direct observation of conspecifics in aversive circumstances.
Observational fear learning has been shown to occur in some nonhuman primates and a few other
vertebrates, such as birds and rodents (see [43] for a review).
In a typical instructed fear study, a participant is told she/he might receive a shock when presented
a neutral stimulus (the instructed CS). This symbolic communication of threat has been shown to lead
to robust fears that are difficult to distinguish from those learned through direct aversive experience
[44]. One of the few differences is that Pavlovian CS’s biologically “prepared” by evolution to yield
more lasting fear responses (e.g., spiders, snakes, angry faces) will continue to show fear expression
when presented subliminally (see [20] for a review). In contrast, awareness of the presentation of
the instructed CS is necessary for the expression of instructed fear [45]. Although it is unlikely the
amygdala is the site of storage for the symbolic representation underlying instructed fear, the amygdala
seems to be necessary for instructed fear expression. An fMRI study of instructed fear in which sub-
jects were told which stimulus carried the threat of shock (CS+) and which was safe (CS−) reported
activation of the left amygdala in response to threat versus safe conditions that correlated with the
degree of fear expression [46]. A study examining the effect of right versus left temporal lobectomy
on instructed fear learning found that lesions of the left, but not right, amygdala result in impaired
expression of instructed fear [47]. This left hemisphere lateralization of instructed fear is consistent
with left hemisphere representation of language more broadly. Unlike instructed fear, Pavlovian
conditioned fear has been shown to involve both the right and left amygdala [23, 48].
Like instructed fear, observational fear leads to robust fear responses that are difficult to distin-
guish from Pavlovian conditioning. However, observational fear appears to be more similar in some
ways to Pavlovian fear than instructed fear in that its expression is intact with subliminal presentation
[45]. Furthermore, although being told about potential dangers may not result in an emotional response
unless danger is imminent, observing a conspecific in an aversive circumstance can lead to an empa-
thetic emotional response in the perceiver. For example, Olsson and colleagues [49] showed partici-
pants a video of a confederate undergoing a Pavlovian fear conditioning paradigm to serve as a model
for the procedures the participant would experience in the following session. This comprised the
learning phase. When observing the confederate receiving a shock, the participants showed an increase
in skin conductance and bilateral amygdala activation indicating an emotional response during the
observational fear learning. Consistent with observational fear, the participants also showed a fear
response to the observational CS in the later test session, along with bilateral activation of the
amygdala. Because there is a fear response during learning, as well as later expression of observa-
tional fear, it appears the observation itself acts as a social US, similar to a direct US, such as shock.
Interestingly the strength of expression of observational fear correlated with activation during the
learning phase in the insula, anterior cingulate cortex, and medial prefrontal cortex, regions that have
been implicated in empathy and mentalizing about others [50, 51].
Control of Fear
Research on the neural mechanisms underlying fear learning provides insight in to the mechanisms
underlying anxiety disorders in humans. However, translation of this knowledge into more effective
treatment of fear-related anxiety disorders requires a better understanding of how learned fears
can be diminished. Recent research in both humans and animal models has highlighted several means by
which conditioned fear can be diminished. In this section, we describe the neural mechanisms under-
lying four fear-reduction techniques, extinction, cognitive regulation, active coping, and reconsolida-
tion (Fig. 2).
Extinction
Extinction refers to the gradual decrease in fear expression that typically occurs when a conditioned
stimulus is repeatedly presented without aversive reinforcement [1, 13]. This decrease reflects
the occurrence of a new learned association that the CS that was once predictive of threat is now safe.
The formation of an extinction memory does not overwrite the initial fear association between the CS
and this aversive outcome, as evidenced by the fact that fear expression can return following extinc-
tion under a number of circumstances (see review by [13]). The term renewal refers to the return of
fear following reexposure to the context in which an extinguished fear memory was initially learned.
Reinstatement is the return of expression of an extinguished fear that occurs after the unsignalled
presentation of the aversive unconditioned stimulus. Spontaneous recovery refers to the increase in
fear expression that typically occurs following extinction with the mere passage of time. These situations
in which extinguished fear reemerges suggest that extinction memory and the original fear memory
a Fear Extinction b Cognitive Regulation

dlPFC
vmPFC
Amygdala Amygdala
IL
vmPFC
ITC ITC
IL
CE CE
PL
BA PL BA
Brainstem/ Brainstem/
Hypothalamus Hypothalamus
LA LA
Hippocampus
Sensory Input Fear Expression Sensory Input Fear Expression

[CS-US] [CS-US]
c Active Coping d Reconsolidation

vmPFC
Amygdala Amygdala
IL Striatum
ITC ITC
CE CE
PL
BA BA
Brainstem/ Brainstem/
Hypothalamus Hypothalamus
LA LA
Sensory Input Fear Expression Sensory Input Fear Expression

[CS-US] [CS-US]
Fig. 2 Neural mechanisms of changing conditioned fear. (a) During fear extinction learning and consolidation, connec-
tions are established between the infralimbic (IL) subregion of the vmPFC and the inhibitory intercalated (ITC) cell
masses, which inhibit activity in the CE. During extinction recall, these connections are activated, inhibiting fear expres-
sion. The IL and PL inhibit one another, mediating the competition between the fear and extinction memory for expres-
sion. Contextual modulation of extinction expression is mediated by projections from the hippocampus to the vmPFC
and/or LA. (b) During cognitive regulation, the dorsolateral prefrontal cortex (dlPFC) regulates fear expression through
projections to the vmPFC, which in turn inhibits amygdala activity. (c) During active coping, information from the LA is
routed not to the CE, which drives fear expression, but to the B, which in turn projects to the striatum. The striatum is
thought to reinforce instrumental action taken during instrumental learning. Following active coping, changes occur in
the vmPFC such that it is activated by subsequent exposure to a stressor, inhibiting the fear response. (d) Reconsolidation
diminishes conditioned fear expression through alteration of the original CS–US association stored in the LA
are engaged in a competition to determine which controls the behavior of the organism, a view that is
consistent with our current understanding of the neurocircuitry supporting fear extinction.
Studies in animal models have made substantial progress in clarifying the neural circuits that
underlie extinction learning (Fig. 2a). This research suggests that the acquisition of initial extinction
learning, like the original fear memory, depends upon the amygdala. Pharmacological blockade of
NMDA and glutamate signaling or mitogen-activated protein kinase (MAPk) activity within the basal
and lateral nuclei or basolateral amygdala complex (BLA) impairs extinction learning [52–54]. BLA
synapses appear to exhibit plastic changes following extinction training that support the consolidation
of the extinction memory [55–58].
While the amygdala appears necessary for the initial acquisition of extinction learning, the ventro-
medial prefrontal cortex (vmPFC) plays a critical role in both the consolidation and retrieval of extinc-
tion memory (see [59] for a review) (Fig. 2a). While not essential for the initial acquisition of extinction
learning [15], evidence from electrophysiological, pharmacological inactivation, and lesion studies
implicates the infralimbic region (IL) of the vmPFC as a site of extinction consolidation [15, 60–62].
Following initial learning, the retrieval of extinction memory is mediated by the IL, which inhibits
conditioned fear expression via its projections to the intercalated cell masses (ITC) within the
amygdala, which in turn have inhibitory projections to the CE [63–65]. Projections from the
hippocampus to the vmPFC and the amygdala appear to mediate the context-dependent expression of
extinction [66, 67], providing information that determines whether extinction learning is retrieved or
the original fear memory returns (see [13] for a review).
Growing evidence suggests that following extinction, distinct amygdala–prefrontal subnetworks
control whether extinction memory or fear memory is expressed (see [68] for a review). A recent
study demonstrated that distinct populations of cells within the BA are responsive to CS presentation
during fear expression and extinction retrieval and that this region mediates the switches between
these high and low fear states [69]. The BA is proposed to drive or inhibit fear expression in concert
with the PL and IL prefrontal regions, respectively [68]. Further research is required to elucidate
the detailed dynamics of this competition for behavioral control; however, this model suggests how
the same CS may give rise to opposing behavioral responses depending on the available information
about the contextual circumstances.
Studies in rodents have highlighted pronounced changes in extinction learning across develop-
ment. Following extinction learning, post-weanling rats (24 days old) exhibit contextual renewal,
spontaneous recovery, and reinstatement of conditioned fear, suggesting the existence of competing
threat and safety memories; however, pre-weanling animals show none of these fear reemergence
phenomena [70–72]. Unlike in adults, extinction learning in these pre-weanling animals does not
recruit the vmPFC [73] but instead appears to overwrite the initial fear memory within the amygdala
[72, 74]. This suggests that early-life extinction may yield fear erasure, suggesting a developmental
window of opportunity for the treatment of fears acquired early in life. In contrast, adolescent rats
show impaired retention of extinction learning [75, 76], suggesting that adolescence may represent a
period of vulnerability to persistent fear.
An early functional neuroimaging study of extinction learning in humans [27] used a two-day
paradigm in which subjects learned to discriminate between a visual CS+ and CS− on day one and
then immediately underwent extinction, during which the CS+ was no longer paired with shock. On
day two, subjects returned for a second extinction session to assess the retention of their extinction
learning. This study reported increases in BOLD signal in a subgenual anterior cingulate/vmPFC
region during initial extinction learning, as well as a corresponding decrease in amygdala BOLD
activation. Further increases in vmPFC BOLD activation were observed during extinction recall on
the following day [27]. Subsequent fMRI studies of extinction have also reported increased activation
in the vmPFC during extinction retrieval [77, 78]. Furthermore, both the magnitude of vmPFC BOLD
signal and the thickness of the cortex in this region have been found to correlate with the degree of
extinction retrieval [78–80]. These findings suggest that this subgenual ACC/vmPFC region may be a
human homologue of the rodent IL region and may directly inhibit fear expression via projections to
the amygdala.
Studies in humans corroborate the role of the hippocampus in the context-dependent retrieval of
extinction [77, 78]. Using a paradigm in which extinction learning is associated with a distinct visu-
ally identifiable context, increases in hippocampal BOLD activation were reported during extinction
retrieval [77, 78]. Consistent with the evidence that the hippocampus mediates the context-dependent
recall of extinction via connections with the vmPFC, hippocampal BOLD activation correlated posi-
tively with vmPFC activation [78]. Finally, individuals with hippocampal lesions show impaired
context-dependent fear reinstatement [81], a finding that parallels observations in rodents [82].
In summary, studies examining extinction learning in humans have been largely consistent with the
findings in animal models, suggesting that the underlying neurocircuitry is conserved across species.
Extinction-based techniques are commonly employed in cognitive-behavioral therapy to treat anx-
iety disorders. Exposure therapy involves establishing prolonged contact with the specific stimuli,
thoughts, or experiences that elicit anxiety in a safe context [83]. As the current models of extinction
suggest, this process may result in the formation of a new safety memory that may override the
expression of the fear memory. Thus, the ability to acquire and consolidate extinction learning may be
critical for successful treatment. Consistent with this notion, a recent study reported that degree of
extinction retention between exposure sessions predicted the long-term efficacy of treatment at reducing
anxiety symptoms [84]. Furthermore, exposure therapy outcomes are improved by the administration
of d-cycloserine, a drug that enhances extinction learning [85, 86]. A number of pharmacological
agents have been identified that facilitate extinction learning in rodents [87], suggesting promise for
the development of drug treatments that enhance the efficacy of exposure therapy.
Cognitive Regulation
While research in animal models has critically informed our understanding of how fear is attenuated
during extinction, humans also regularly use an array of cognitive regulatory techniques to modulate
emotional responses. Cognitive regulation refers to a range of automatic and intentional mechanisms
by which thoughts are used to change emotions [88, 89]. Prominent theories propose that emotional
responses arise when we attend to a stimulus and judge it to be motivationally significant [90, 91].
These models suggest that our allocation of attention and the manner in which we ascribe meaning to
an event can be important determinants of our emotional experiences. Accordingly, recent studies in
humans have demonstrated that intentional cognitive regulation techniques can be used to diminish
negative emotional responses and have suggested a provisional model of the neurocircuitry underly-
ing these effects [92, 93].
An early neuroimaging study of cognitive emotion regulation examined whether changes in our
appraisal of a potentially unpleasant stimulus could diminish negative emotional responses [94]; see
also [95]. In this study, participants viewed images with negative emotional content and were instructed
to reinterpret the scene in a more positive manner, reducing their emotional response. For example, a
participant viewing an image of a grieving man might instead interpret the scene as depicting a man
shedding tears of joy at wedding. This “reappraisal” technique, in which the individual changes the
affective significance of a stimulus, also reduced subjects’ ratings of negative affect [94]. This study
provided a preliminary outline of the neural mechanisms underlying the cognitive regulation of nega-
tive affect. The neuroimaging data showed that during reappraisal of the negative scenes, in comparison
to simply attending to them, BOLD activation in the amygdala decreased, while activation in both
dorsolateral (dlPFC) and ventrolateral (vlPFC) prefrontal cortex increased [94].
Several subsequent studies employing similar cognitive regulation techniques have observed
reductions in self-reports and physiological measures of negative affect evoked by diverse stimuli
including unpleasant pictures and films (see [93] for a review) and even aversion to monetary loss [96,
97]. Those studies that conducted functional imaging of these tasks largely confirm the provisional
neurocircuitry described above, in which regulation evokes an increase in BOLD activation in dlPFC
and/or vlPFC accompanied by a decrease in amygdala activity that mirrors the associated decrease in
negative affect (see [93, 98] (Fig. 2b)). The interpretation of this pattern of activation is that engage-
ment of the dlPFC reflects executive control processes involved in carrying out the cognitive strategy,
while the vlPFC is involved in the selection of the novel emotional interpretation of the stimulus [92,
98]. The reduction in amygdala activation is typically interpreted as evidence of successful deploy-
ment of a top-down control process that changes the affective value of the stimulus and the associated
measure of negative affect. However, one neuroanatomical conflict with this model is that the dorso-
lateral prefrontal cortex does not have direct projections to the amygdala [5, 99]. One suggestion is
that ventromedial prefrontal regions may mediate the reduction in amygdala activity via strong pro-
jections to this region [100, 101]. Thus, cognitive regulation may recruit the same vmPFC–amygdala
neurocircuitry implicated in attenuating fear following extinction learning.
A recent study directly examined whether intentional cognitive regulatory strategies and fear
extinction share overlapping neural substrates [102]. In this study, participants viewed conditioned
stimuli that were colored squares while instructed to either attend to their natural response or regulate
these responses by generating a pleasant mental image of something soothing in nature associated
with the CS color. Conditioned responses in the regulation condition were significantly lower than
when participants simply attended to their anticipatory responses. This reduction in fear was accom-
panied by decreased amygdala activity and increased activity in both the dlPFC and a region of the
vmPFC that, when compared to a previous study of extinction learning, overlapped with a region
activated during extinction. Furthermore, activity in the vmPFC was correlated with that of the
amygdala and dlPFC, providing further evidence that dlPFC inhibition of amygdala activity is medi-
ated by the vmPFC. Thus, despite the fact that the regulation of fear through the use of cognitive
strategies may be unique to humans, this suggests that cognitive fear regulation recruits the same
vmPFC–amygdala extinction circuitry that is evolutionarily conserved across species.
Few studies have examined the use of cognitive regulation strategies to reduce negative affect in
individuals with anxiety disorders [103, 104]. However, two recent neuroimaging studies highlight
differences in the functioning of the neurocircuitry supporting cognitive regulation between patients
and healthy individuals. In these studies [105, 106], cognitive regulation of emotional responses to
negative stimuli (negative self-beliefs and physical and social threat-related images) was effective in
reducing both ratings of negative affect and neural activity in the amygdala in both healthy controls
and patients with social anxiety disorder. However, activity in prefrontal regions differed between
controls and patients. While controls show robust early activity in dlPFC and vmPFC that decreased
over trials, patients displayed increases in these regions across time with both smaller and later peaks.
Furthermore, analysis of regions correlated with amygdala activity during regulation revealed a greater
extent of the dlPFC inversely correlated with amygdala activity in controls than in patients [106].
Cognitive therapy techniques taught in a clinical context encourage individuals with anxiety or
depression to overcome their biases toward negative situational appraisals, thus diminishing their cor-
responding negative emotional responses [107]. Experimental studies of cognitive regulation in the
laboratory delineate the neural pathways through which this regulation takes place. While the deploy-
ment of cognitive regulation techniques may be improved through instruction and practice, the
efficacy of treatment of fear-related disorders via cognitive therapy may depend on the functional and
structural integrity of the prefrontal–amygdala regulatory neurocircuitry [108]. The structural integ-
rity of the white matter tract that comprises this inhibitory pathway varies between individuals and is
inversely correlated with trait anxiety [109]. Such individual variation may contribute significantly to
the heterogeneity in individual responses to clinical cognitive interventions.
Active Coping
To date, experimental research on the control of fear has focused primarily on how cognitive pro-
cesses, such as implicit safety learning during extinction or intentional cognitive regulation, can
alter fear expression. However, a common means by which we regulate our emotions in everyday
life is through the performance of actions that improve our emotional state. The term “active coping”
can refer to any action taken to mitigate or avoid aversive experiences or to bring about a positive
experience.
Actively coping with a fear-eliciting stimulus requires a sequence of distinct learning processes.
First, one must learn that a stimulus or a context poses a threat via the formation of a Pavlovian fear
association. Next, the exercise of control over the fear-eliciting situation requires that one learn an
action that can be taken to avoid or escape the feared stimulus. Finally, recent research suggests that
neural changes occurring following the exercise of control over a stressor diminish subsequent fear
expression [110] and buffer the effects of future exposure to uncontrollable stressors [111]. Through
these processes, active coping enables the modulation of fear responses to both present and future
aversive situations.
Relative to other fear-reduction techniques, our understanding of the neural substrates that support
actively coping with fear is rudimentary. However, existing studies provide a provisional model of
the neural circuits involved in each stage of the active coping process (Fig. 2c). As described above,
once a Pavlovian fear memory has been learned, the presentation of a conditioned stimulus activates
the LA, which in turn activates the CE, triggering fear expression via descending projections to the
brainstem and hypothalamus. Evidence that an alternative amygdala pathway plays a critical role in
instrumental learning phase comes from a study employing an escape from fear (EFF) task, in which
an instrumental response terminates exposure to a tone CS that was previously paired with shock
[112]. This study showed that lesions to the CE impaired the expression of the Pavlovian conditioned
freezing response. Lesions to the BA prevented the acquisition of an EFF avoidance response. Lesions
to the LA prevent both fear expression and instrumental learning, suggesting that the LA plays a criti-
cal role in both Pavlovian and instrumental learning. The LA projects to the BA, which in turn has
striatal projections that play a key role in instrumental reinforcement learning [113]. Engaging the
LA–BA pathway likely guides instrumental learning in the EFF task by providing conditioned rein-
forcement signals that motivate the avoidance response.
In contrast, engagement of the LA–CE pathway, which drives fear expression, may prevent the
performance of active coping behavior. In an active avoidance task in which rats had to learn to shuttle
across a chamber in order to avoid a shock [114], post-training lesions of the CE had no effect on
shuttling behavior in animals that had learned to avoid the shock. Surprisingly, in animals that had not
learned to consistently avoid the shock, lesions to the CE revealed that they had indeed learned the
avoidance contingency. When the CE-mediated freezing response was disengaged, these animals
were then able to perform the avoidance response. This suggests that excessive fear may impair active
coping by preferentially engaging defensive Pavlovian responses.
The experience of control over a stressor that occurs during active coping appears to foster resil-
ience to subsequent stressors, reducing fear-related behavior even in future uncontrollable situations
[111]. Studies demonstrating this effect used a triadic design, in which rats were first exposed to
escapable shock, yoked inescapable shock of identical intensity and duration of that experienced by a
paired individual in the escapable condition, but that could not be escaped, or a control condition
involving no shock exposure. One week later, these animals underwent fear conditioning [110].
Exposure to inescapable stress increased conditioned fear in comparison to control animals. However,
surprisingly, animals exposed to controllable shock exhibited less fear than animals with no prior
shock exposure, suggesting the experience of controllable stress inhibited subsequent fear. Evidence
suggests that the vmPFC mediates the effects of prior behavioral control on future stressor-evoked
behavior. Inactivation of the vmPFC during controllable stress or during exposure to a subsequent
stressor negates the effects of controllability on later behavior [115, 116]. Either the vmPFC or an
afferent input region appears to detect when a stressor is under an organism’s instrumental control
and, in turn, inhibits the physiological and behavioral effects of uncontrollable stress [115].
Furthermore, the experience of controllable stress appears to give rise to long-term changes in the
vmPFC that enable it to be activated during subsequent uncontrollable stress, regulating the behav-
ioral response [117]. The IL subregion of the vmPFC is activated by controllable stress [118] and may
later inhibit the CE directly, mitigating fear expression [116].
Consistent with this notion that control over stressors engages the same vmPFC–amygdala path-
way active during extinction retrieval, active coping appears to prevent the spontaneous recovery of
fear [110, 119]. In one such demonstration [119], animals first were fear conditioned; then one group
of animals learned an EFF response, terminating exposure to a tone CS, while a second group received
yoked tone exposure, essentially undergoing classic extinction. Both groups showed reduced fear
during their respective learning phase; however, in a subsequent retrieval test, the extinction group
showed the typical recovery of fear, while the group that had learned an active coping response did
not. A major shortcoming of the extinction-based therapies that are typically used to treat fear-related
anxiety is that extinguished fears often reemerge. This finding suggests that therapeutic approaches
employing active coping techniques may yield a more lasting reduction in fear.
Few studies have explored fear reduction through active coping in humans; however, the preliminary
data suggest that the underlying neurocircuitry is shared across species. An fMRI study examining the
neural substrates of avoidance learning found that when subjects learned to avoid a shock by perform-
ing a key press during CS presentation, performance of this response led to an increase in striatal
activation, as well as a decrease in amygdala activation that was accompanied by a reduction in fear
expression [120].
Given that the avoidance of fear-eliciting situations is a hallmark of anxiety disorders, the notion
that avoidance behaviors might foster resilience might appear counterintuitive and warrants clarification.
Avoidance of a stressor can occur through either a passive or active route. A passive avoidance response
involves withdrawal from threat, preventing encounters with a fear-eliciting stimulus through the sup-
pression of thoughts or behavior, akin to the freezing response displayed by rodents. In contrast, an
organism may show a proactive exploratory avoidance response, attempting to escape or “disarm” a
present threat through action. Evidence from studies in rodents suggests that individuals may show
stable biases toward active or passive coping styles [121], and a recent study suggests that a bias toward
active or passive fear responses may be determined by the function of an intra-amygdalar circuit [122].
While cognitive-behavioral therapy often aims to reduce avoidance behavior, research suggests that the
active type of avoidance response may be adaptive, yielding long-term resilience. Thus, it may be that
forms of avoidance behavior that engage the individual in action to directly mitigate the aversiveness
of a feared object or situation have beneficial consequences. An important area for future investigation
is to examine the effect of active versus passive coping responses (including active avoidance behavior)
in humans to clarify its effects on subsequent fear expression.
Reconsolidation
All of the techniques to diminish fear described above control the fear response through inhibition
of the amygdala via the prefrontal cortex. Although these techniques can be very effective, they leave
the amygdala’s fear representation largely intact. As described earlier in the section on extinction, one
consequence is that the fear can return under a range of circumstances. In the clinic, this intact fear
representation may be an important factor linked to the potential for relapse following successful
treatment. Due to this limitation, there has been growing interest in emerging techniques to target the
amygdala’s fear representation by influencing memory reconsolidation.
Reconsolidation refers to a process by which a previously consolidated memory is brought back to
a fragile or labile state when retrieved and requires a second consolidation process, or reconsolidation,
for re-storage. For most of the last century, the standard model of memory suggested that immediately
after information is learned, it is fragile and prone to disruption because the synaptic processes that
form the memory require time. This memory formation process is called consolidation. However,
once a memory has been fully consolidated, it was assumed that the memory was stable and no longer
prone to disruption. New learning about a stimulus could create a second memory trace, but the original
memory trace was still intact. Over the last decade, however, there has been renewed interest in the
notion that every time a memory is retrieved, it is once again in a fragile state and requires a second
consolidation process, or reconsolidation, and new synaptic plasticity to once again become stable.
If memory is fragile after retrieval, this provides a second opportunity to potentially disrupt or perma-
nently alter the memory before it is reconsolidated. In the case of fear memories, this provides an
avenue to alter the original fear memory, as opposed to inhibit its expression (Fig. 2d).
Initial evidence for fear memory reconsolidation was provided in a seminal study by Nader and
colleagues [123]. As mentioned earlier, the LA is thought to be the site of fear memory storage. Nader
and colleagues hypothesized that if fear memory reconsolidation requires new synaptic plasticity,
which requires protein synthesis, then injecting a protein synthesis inhibitor into the LA after retrieval
should prevent reconsolidation and permanently alter the original fear memory. To test this, they con-
ditioned rats to fear a tone CS. After initial consolidation of this fear memory, the rats were exposed
to the tone again to reactivate the memory. This was immediately followed by administration of the
protein synthesis inhibitor anisomycin into the lateral amygdala. A day later, the conditioned fear
response was assessed. The rats that received the injection immediately after cue retrieval showed
reduced expression of conditioned fear in comparison to rats receiving placebo, no reminder and
injection of the drug, or injection of the drug 6 h after the reminder cue when the reconsolidation
process was complete.
Since this study, there have been hundreds of studies in nonhuman animals investigating the mech-
anisms of fear memory reconsolidation. This research has basically supported these initial findings
suggesting that the original fear memory is significantly altered by targeting reconsolidation, although
some important distinctions in both the temporal molecular requirements and the brain regions
involved in reconsolidation and initial consolidation have emerged (see [124] for a review).
In humans, however, there has been less success in demonstrating fear disruption by targeting
reconsolidation. A primary reason is that the protein synthesis inhibitors typically used to target recon-
solidation in other species have not been verified as safe for use in humans. In an effort to introduce a
safe pharmacological intervention, Debiec and LeDoux [125] examined whether propranolol, a beta-
adrenergic blocker that has been shown disrupt some forms of amygdala-dependent consolidation
[126], would also disrupt fear memory reconsolidation. Propranolol is commonly prescribed to help
with stage fright and has also been used in treating high blood pressure. Using both systemic and
intra-amygdala injections in rats, they showed administering propranolol immediately after fear mem-
ory reactivation abolished the conditioned fear response at later test. Unfortunately, studies examining
the efficacy of propranolol in human fear memory reconsolidation have been mixed. In an initial
attempt, Brunet and colleagues [127] administered propranolol after the retrieval of traumatic memo-
ries in patients suffering from post-traumatic stress disorder (PTSD). Although at later test these
patients showed some evidence of diminished physiological fear responses when cued with these
memories, this manipulation did not have a lasting impact on PTSD symptoms. In a laboratory
Pavlovian paradigm examining the influence of propranolol administration after reactivation on later
fear expression found only a transitory reduction of later fear expression (see [128] for a discussion).
Finally, a series of studies examining the impact of propranolol administration prior to cued-fear
memory reactivation found some evidence that later fear expression was impaired but only for a limited
range of fear assessments [129]. In these studies, however, it is possible that the administration of
propranolol prior to fear memory reactivation disrupts a mechanism of fear expression, as opposed to
reconsolidation [130].
Given some of the difficulties of using pharmacological manipulations to target fear memory
reconsolidation in humans, a recent series of studies have used a different approach. These studies
take advantage of the potential adaptive function of reconsolidation. If the purpose of reconsolidation
is to update old memories with new relevant information available at the time of retrieval, then it is
possible that introducing new information during the reconsolidation process will alter the original
memory and have a lasting impact on the memory expression. This basic effect was demonstrated in
humans in a clever series of studies on motor memory, in which introducing a new motor sequence
after reminding participants of a previously learned motor sequence impaired later memory for the
older sequence [131]. In fear learning, this behavioral interference of reconsolidation effect has been
observed in mice [132], rats [133], and humans [134] using extinction training precisely timed to
coincide with memory reconsolidation to interfere with the original fear memory. The primary differ-
ence between using extinction training to update the fear memory during reconsolidation and standard
extinction training is the timing. Fear memory reconsolidation is initiated by the retrieval or reactivation
of the fear cue. After reactivation, it takes somewhere between 3 and 10 min for the reconsolidation
process to begin [133, 134]. If extinction training begins too early, both the return of the fear response
and indicators of synaptic plasticity within the LA [133] are consistent with standard extinction train-
ing. However, if extinction training is slightly delayed until the reconsolidation process has begun, the
fear does not return, in contrast to standard extinction. In addition, changes in the LA under this
behavioral interference protocol suggest learning-induced plasticity consistent with reconsolidation
[133]. In humans, it has been shown that this diminished fear response with behavioral interference
of reconsolidation is apparent even after a year [134]. More recently, in an examination of the molecu-
lar mechanisms underlying this effect, Clem and Huganir [132] demonstrated that the behavioral
interference of reconsolidation might be linked to calcium-permeable AMPA receptor dynamics
within the LA.
Although research on reconsolidation in humans is just emerging, it provides an exciting avenue
for future research because it potentially eliminates the necessity for prefrontal inhibition of the
amygdala. Variation in function of the amygdala–prefrontal pathway has been linked to both the
recovery of fear following extinction and PTSD [135]. As of yet, the efficacy of these techniques has
not been investigated in clinical interventions, and there may be significant limitations, such as the
ability to target specific memories. However, if these techniques prove to be clinically useful, fear
reconsolidation research has the potential to yield more lasting and effective treatments of anxiety
disorders.
Conclusion
Through cross-species research in animal models and in humans, we have obtained a detailed model
of the neurobiological underpinnings of fear learning. As described above, the amygdala plays an
important role in cued, contextual, and social means of fear acquisition, highlighting its central role
in fear acquisition and expression. Additionally, the hippocampus modulates the acquisition and
expression of fear to a context. Drawing upon this detailed neurobiological model of fear conditioning,
research in the past decade on fear extinction has delineated how safety learning following condition-
ing activates a prefrontal–amygdala pathway, inhibiting fear expression [59]. This inhibitory circuit is
also modulated by contextual information relayed via the hippocampus. Notably, cognitive regulation
and active coping, means of fear regulation that differ substantially from extinction, also recruit this
phylogenetically shared inhibitory pathway [136, 137]. However, as these methods inhibit intact fear
memories that can return under certain circumstances, they may all yield a transitory attenuation of
fear. Recent work on reconsolidation suggests that pharmacological or behavioral interference with a
fear memory following retrieval may permanently alter its representation, suggesting a mechanism
for long-term prevention of fear recovery [128].
A central goal of fear research is to understand the origins of pathological anxiety in humans. Fear
conditioning serves as an experimental model for the real-world associative learning that causes stim-
uli in our environment to evoke negative affective responses. Excessive generalization or poor regula-
tion of such learning is proposed to underlie the persistent fear that characterizes anxiety disorders
[138] and may contribute to the biased decision-making associated with these clinical conditions
[139]. While neuroscientific fear research has outlined the mechanisms modulating fear expression in
the typical “average” individual, one important question that remains poorly understood is what gives
rise to the substantial variation between individuals in fear acquisition and regulation. Future research
elucidating how variation in both the genetic and experiential background of the individual shapes the
neurocircuitry governing fear learning will play a critical role in translating fear research from the
laboratory to clinical treatment methods. Furthermore, the small body of research on the developmental
trajectory of fear learning and regulation indicates that there are important qualitative differences in
these processes across development. An improved understanding of the development of fear condi-
tioning will be a necessary step toward understanding the origins of vulnerability to and resilience
against anxiety disorders across the lifespan.
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Neurobiology of Pediatric Anxiety Disorders
Amanda E. Guyer, Carrie L. Masten, and Daniel S. Pine
Abstract Anxiety during childhood and adolescence is a highly prevalent problem that contributes
to long-term dysfunction in adulthood. This chapter highlights research on the neurobiology of pedi-
atric anxiety disorders aimed at understanding how anxiety takes hold in the brain and the mecha-
nisms that fuel its developmental course. We present an overview of anatomical and functional
brain-based differences in children and adolescents with and without anxiety disorders. With regard
to work focused on brain function in pediatric anxiety, we discuss four key psychological processes
that are highly relevant to clinical characteristics in anxiety: attention orienting, threat learning,
social–emotional information processing, and reward processing. We also review recent work that
delineates connections between and within neural regions that appear to be distinctly modulated by
anxiety both in response to specific tasks and while at rest. We close the chapter with a summary of
emerging work on neurobiological response to treatments for anxiety in children and adolescents,
followed by conclusions and future directions for this course of work.
Keywords Anxiety • Adolescence • Childhood • Neuroimaging • Brain structure • Brain function

• Neural connectivity
Introduction
Anxiety disorders are highly prevalent and exert adverse effects on children and adolescents in
both the short and long term [1, 2]. Despite their high prevalence and major impact on functioning
over time, pediatric anxiety disorders have been largely understudied, particularly from a neurosci-
ence perspective [3, 4]. Relative to less common conditions that arise in childhood, such as attention
deficit hyperactivity disorder and autism, far fewer studies examine the pathophysiology of pediatric
anxiety [5].
A.E. Guyer (*)

Department of Human Ecology and Center for Mind and Brain, University of California, Davis, CA, USA
e-mail: aeguyer@ucdavis.edu
C.L. Masten
Department of Psychology and Human Development, Peabody College, Vanderbilt University, Nashville, TN, USA
D.S. Pine
Section on Development and Affective Neuroscience, National Institute of Mental Health, Bethesda, MD, USA
24 A.E. Guyer et al.
This chapter presents four sections that review research on the neurobiology of pediatric anxiety
disorders with an emphasis on neuroimaging studies. First, we briefly introduce the primary brain
regions involved in fear responses. Next, we highlight the development of these regions during child-
hood and adolescence. In the third section, we review neuroimaging findings in pediatric anxiety with
a focus on research directed at mapping relationships among brain function, psychological processes,
and clinical characteristics. In particular, we review four constructs reflecting key cognitive and emo-
tional processes associated with differentiated behavioral and neural responses in anxious and non-
anxious individuals: (1) attention orienting, (2) threat learning, (3) social–emotional information
processing, and (4) reward processing. In the fourth section, we present recent work focused on under-
standing the connections between and within neural regions that appear to be distinctly modulated by
anxiety both in response to specific tasks and while at rest. Finally, we discuss emerging work on
neurobiological responses to treatment for anxiety in children and adolescents.
Discussions throughout this chapter primarily review studies of pediatric samples with one of three
anxiety disorders: generalized anxiety disorder (GAD), social phobia (SoPh), or separation anxiety
disorder (SAD), as they are highly prevalent among children and adolescents [2]. These three disor-
ders also are frequently comorbid and exhibit similarities in many features, such as course and treat-
ment response. As a result, questions remain concerning the degree to which they represent unique
conditions or alternative manifestations of the same underlying syndrome. This chapter reviews data
both on their similarities and differences, although very little research documents clear differences
among these disorders from a neurophysiological perspective. Thus, in the following discussion, we
refer to these disorders together as “pediatric anxiety.”
While other anxiety disorders occur in children, they are not the focus of this chapter. Obsessive-
compulsive disorder (OCD) and post-traumatic stress disorder (PTSD) are not a main focus here
given their unique pathophysiological profiles. Similarly, panic disorder is rare before late adoles-
cence and accordingly is only minimally discussed. Finally, specific phobia is not discussed as it has
been the focus of very little neurobiological research with children. For in-depth discussion about
these disorders, readers are referred to Chaps. 9 and 10 in this volume. In addition, given our focus on
neuroimaging and pediatric anxiety, the research reviewed herein primarily focuses on studies of
individuals in late childhood through late adolescence given greater availability of research published
in this age range relative to younger ages.
Brain Regions Implicated in Fear Processing
Considerable work has delineated the engagement of a neural fear circuitry that processes and guides
responses to threat in one’s surroundings [6–8]. In this basic science work, the term “threat” refers to
collections of cues that signal the presence of danger to the organism. When such threats are proximal,
immediately present, and extremely dangerous, they are thought to evoke a state of “fear” in the
organism; when they are more distal, less immediate, and more ambiguous in terms of their danger-
ousness, they evoke a state of “anxiety.” Such work provides useful cross-species models for under-
standing the neurobiology of threat processing, fear, and anxiety responses in humans across various
stages of development [3, 9]. Drawing on research in both animals and humans, the neural circuitry
implicated in threat processing and fear-related behaviors centers on the amygdala, located in the
medial temporal lobe, as well as the ventral prefrontal cortex (vPFC). The amygdala aids in process-
ing information about salient stimuli either positive or negative in valence and in mediating emotional
responses [10–12]. The vPFC encompasses at least two subregions [13]. One of these subregions
encompasses the lateral PFC and is involved in attention control along with other related processes.
The other subregion encompasses the medial PFC, which has been implicated in fear extinction.
Neurobiology of Pediatric Anxiety Disorders 25
Lesion studies have confirmed hypotheses about the amygdala’s role in processing stimuli that
signify threat and translating reactions to fear-induced behaviors. For example, the application of
lesions to the amygdala in nonhuman primates results in decreases in anxious behavior and blunted
fear responses [6, 14, 15]. Similarly, a series of studies in humans show that adults with amygdala
lesions cannot recognize fearful facial expressions, despite the ability to identify other facial expres-
sions of emotion [7, 16, 17].
Facets of Brain Development Relevant to Pediatric Anxiety
Adolescence is a period of heightened emotionality and cognitive-regulatory changes driven in part

by maturation of brain structures and their functions [18]. Subcortical brain structures that support
basic functions such as detecting danger and safety in the environment (e.g., the amygdala) and form-
ing memories that guide future behavior (e.g., the hippocampus) follow a relatively early maturational
trajectory given their role in human survival [19]. Cortical brain structures such as the prefrontal cor-
tex (PFC) show a more prolonged and continued maturation pattern across adolescence and into early
adulthood. During this time, the PFC shows a decline in gray matter volume reflecting the pruning of
unused and unnecessary neural circuits [20] and an increase in white matter as signal transmission
becomes faster and more efficient [21]. Such a prolonged maturational period suggests that frontal
brain areas do not reach full functional status until late adolescence or early adulthood [22]. Thus,
adolescents may be vulnerable to the onset of mental illnesses such as anxiety and depression due to
immaturity of PFC-based cognitive-regulatory functions [23]. Indeed, adolescents in the middle-late
stages of puberty relative to those in early stages of puberty show altered patterns of amygdala and
ventrolateral PFC responses that vary based on the emotional and social nature of stimuli and that
relate to negative affect and mood [24].
Because the amygdala and associated projections are implicated in the detection and evaluation of
potentially threatening stimuli [6, 25], developmental changes in structural characteristics of the
amygdala should be considered with regard to understanding the emergence of pediatric anxiety. For
example, the rate of amygdala growth in the nonhuman primate is most accelerated within the early
postnatal period after which amygdala growth begins to decelerate and flatten [26]. The timing of
damage to the amygdala also shows unique effects on fear responses as a function of development.
For example, amygdala lesions applied to monkeys in adulthood result in reduced social fears, whereas
such lesions applied in childhood lead to increased social fears [27]. In humans, structural changes in
the amygdala generally extend from one year of age into late childhood [19]. Sex differences have
also been noted in amygdala development, whereby females show adult volumes by age 4 and males
show continued amygdala volume growth from ages 4 to 18 [28–30]. Finally, as amygdalo-cortical
fibers thicken in adolescence, better regulatory control with respect to harm avoidant behaviors may
be coming online [31].
Brain Function in Pediatric Anxiety
Before beginning discussion of studies of brain function, it is important to review the two published
studies of brain morphology in pediatric anxiety. These studies, which include early adolescent sam-
ples, have reported discrepant results. Specifically, compared to samples of typically developing
children, youth with GAD exhibited greater amygdala volumes [32], whereas reduced amygdala vol-
ume was identified in adolescents with GAD, SAD, or SoPh [33]. Morphometry of other regions has
also differentiated healthy youth from those with anxiety. Notable patterns in children with anxiety
Brain Psychological
Phenotype
Circuitry Processes
Ventromedial Attention Orienting

PFC and Generalized
Amygdala Anxiety
Threat Learning
Genes
Circuit Social Phobia

Separation Anxiety
PFC and Reward Processing Early childhood
Striatum Circuit behavioral
Social-Emotional inhibition
Information-
Dorsal PFC Processing
Circuit (emotional faces,
social evaluation)
Maturational and environmental influences
Fig. 1 A schematic framework of the mechanisms underlying associations among brain circuitry, psychological pro-
cesses, and phenotypes, accounting for the influences of genes, environments, and maturation. PFC prefrontal cortex
compared to healthy comparisons show larger superior temporal gyrus [34] and decreased volume of
the ventrolateral PFC and precuneus [33]. While these studies provide preliminary evidence of struc-
tural differences associated with pediatric anxiety, more work is clearly needed to elucidate character-
istic structural perturbations of these disorders.
Relative to the number of structural neuroimaging studies in pediatric anxiety, functional neu-
roimaging studies are a burgeoning area. A goal of this work is to link neural function with psycho-
logical processes that are characteristic of specific anxiety phenotypes and symptoms, while also
accounting for genetic, maturational, and environmental influences (see Fig. 1) [4]. In pediatric anxi-
ety, it has been hypothesized that both fear and reward circuits are involved. Thus, much of the func-
tional neuroimaging work in children and adolescents has examined amygdala function in response
to threatening stimuli such as fearful or angry faces. However, intriguing findings are now emerging
in pediatric anxiety regarding the role of the striatum and vPFC, which support reward processing
and regulatory processes that may provide new avenues of research on, and treatment approaches for,
pediatric anxiety.
In this section, we highlight evidence gathered from a growing body of work that uses functional
magnetic resonance imaging (fMRI) to examine the neural substrates of different psychological pro-
cesses relevant to the symptoms of anxiety in children and adolescents. FMRI has proven to be a
useful technique to pursue these investigations because of its excellent temporal and spatial resolu-
tion. In addition, fMRI procedures are safe, noninvasive, and tolerable for use with young popula-
tions. Below we focus on pediatric fMRI studies that assess the neural correlates of core anxiety-related
cognitive and affective processes including attention orienting, threat learning, social–emotional
information processing, and reward processing (refer to Table 1 [35–52] for study details). Many of
these studies use faces depicting emotional states as stimuli as well as other emotionally evocative
(but not extremely frightening) stimuli. These stimulus types are generally used with pediatric popu-
lations in order to (1) adhere to ethical research designs due to potential harm from exposure to
extremely threatening or frightening stimuli; (2) remove confounds introduced by word-based stimuli
that may be associated with age-related differences in emotional and linguistic processing abilities;
(3) consistently and reliably capture attention; and (4) represent stimuli encountered regularly by
children in their daily lives.
Table 1 Functional neuroimaging studies including children and adolescents with anxiety diagnoses, anxiety symptoms,
or risk for anxiety
Study Sample demographics Anxiety status Task
Attention orienting
Monk et al. Age range: 9–17 years Generalized anxiety Attention to angry faces
[35] Patient group: n = 18, 8 females disorder using a dot-probe task
Healthy group: n = 15, 8 females
Monk et al. Age range: 11–16 years Generalized anxiety Attention to masked angry
[36] Patient group: n = 17, 6 females disorder faces using a dot-probe
Healthy group: n = 12, 6 females task
Telzer et al. Age range: 11–18 years Trait anxiety Attention to angry faces
[37] Healthy group: n = 16, 8 females using a dot-probe task
Social–emotional information processing
Face emotion processing
Thomas et al. Age range: 8–16 years Generalized anxiety Fearful face processing using
[38] Patient group: n = 12, 5 females disorder and/or panic a passive viewing face
Healthy group: n = 12, 5 females disorder emotion task
Anxiety symptom severity
Killgore and Age range: 8–15 years Anxiety symptom severity Fearful face processing using
Yurgelun- Healthy group: n = 16, 7 females a passive viewing face
Todd [39] emotion task
McClure et al. Age range: 10–14 years Generalized anxiety Attention to subjective fear
[40] Patient group: n = 17, 7 females disorder of fearful faces using an
Healthy group: n = 20, 11 females attention–emotion face
task
Perez-Edgar Age Range: 10–15 years Risk for anxiety Attention to subjective fear
et al. [41] Behaviorally inhibited group: of fearful faces using an
n = 10, 8 females attention–emotion face
Non-Inhibited group: n = 17, 9 task
females
Beesdo et al. Age range: 11–16 years Generalized anxiety Attention to subjective fear
[42] Anxiety no MDD: n = 16, 5 disorder, social phobia, of fearful faces using an
females separation anxiety attention–emotion face
MDD no anxiety: n = 12, 7 females disorder, and/or major task
MDD with or without anxiety: depressive disorder
n = 26, 15 females
Healthy controls: n = 45, 24
females
Lau et al. [43] Age range: 10–16 years Generalized anxiety Attention to subjective fear
Patient group: n = 31, 18 females disorder, social phobia, of fearful faces using an
Healthy controls: n = 33, 18 separation anxiety attention–emotion face
females disorder, and/or major task
depressive disorder
Blair et al. Age range: 9–41 years Social phobia Gender judgment of faces
[44] Patient group: n = 39, 14 adoles- using a morphed facial
cents, 22 females emotion task
Healthy group: n = 39, 16
adolescents, 17 females
Social evaluation processing
Guyer et al. Age range: 9–15 years Social phobia, generalized Anticipation of peer
[45] Patient group: n = 14, 10 females anxiety evaluation using the
Healthy group: n = 14, 10 females disorder + social chat room task
concerns, and/or
separation anxiety
disorder + social
concerns
(continued)
Table 1 (continued)
Study Sample demographics Anxiety status Task
Lau et al. [46] Age range: 9–14 years Social phobia, generalized Receipt of peer evaluation
Patient group: n = 12, 8 females anxiety using the chat room task
Healthy group: n = 12, 8 females disorder + social
concerns, and/or
separation anxiety
disorder + social
concerns
McClure- Age range: 10–15 years Generalized anxiety Betrayal and cooperation
Tone et al. Patient group: n = 12, 7 females disorder, social phobia, using a Prisoner’s
[47] Healthy group: n = 17, 8 females and/or separation Dilemma task
anxiety disorder
Reward processing
Guyer et al. Age range: 10–15 years Risk for anxiety Response to anticipated
[48] Behaviorally Inhibited Group: incentives using the
n = 13, 8 females monetary incentive delay
Non-inhibited group: n = 19, 10 task
females
Krain et al. Age range: 13–17 years Generalized anxiety Intolerance to uncertainty
[49] Patient group: n = 16, 7 females disorder and/or social using the Hi/Lo
Control group: n = 13, 8 females phobia decision-making task
Bar-Haim Age range: 14–18 years Risk for anxiety Response to anticipated
et al. [50] 15 females incentives using a reward
Behaviorally inhibited group: contingency task
n = 16, 5 females
Non-inhibited group: n = 16, 10
females
Helfinstein Age range: 14–18 years Risk for anxiety Response to incentive
et al. [51] Behaviorally inhibited group: outcomes using a reward
n = 16, 5 females contingency task
Non-Inhibited group: n = 16, 10
females
Guyer et al. Age range: 10–16 years Generalized anxiety Response to anticipated
[52] GAD group: n = 18, 10 females disorder and/or social incentives using the
Social phobia group: n = 14, 9 phobia monetary incentive delay
females task
Healthy group: n = 26, 11 females
Attention Orienting
Attention orienting is a process that involves focusing one’s attention on salient stimuli. A central
feature of anxiety and fear-related behavior is atypical modulation of attention that manifests as
hypervigilance and enhanced attention to threatening stimuli, referred to as attentional bias [53–55].
The specific role of this attention bias in the etiology and/or maintenance of pediatric anxiety disor-
ders is unknown. However, recent randomized controlled trials have demonstrated that training anx-
ious children to modify their attentional threat biases can facilitate disengagement of attention to
threat, which in turn can reduce anxiety symptoms [56, 57]. These findings imply a direct link between
attention bias towards threat and anxiety symptoms. Further, they suggest that attention biases might
emerge over time through reinforcement or as a means to reconcile ambiguous situations [58].
Several paradigms (e.g., dot-probe tasks, emotional Stroop tasks) have been used to manipulate
attention orienting and measure how anxious individuals orient their attention to threat stimuli, such
Masked Faces
+
*
Unmasked Faces
Fixation:
Fixation: Stimulus type: Response cue:
500
500ms
ms 17-2500 ms 1500 ms
Time
Fig. 2 An example of a trial in the dot-probe paradigm used to measure the influence of threats on attention orienting.
A fixation cue is presented first. Then, pairs of stimuli depicting threat or nonthreat cues are presented. Stimulus pairs
may be presented for varying time durations (e.g., 17–2,500 ms). Finally, a dot-probe cue appears to which participants
respond via a button press. Attention bias to threat can be assessed through the time it takes to respond to the dot-probe
cue as well as associated changes in neural response to the cue
as pictures of angry faces or words connoting threat [4, 53, 54]. Variants of the dot-probe task (see
Fig. 2) have been the most widely used approaches to assess attention biases, particularly in studies
of pediatric anxiety and health [35, 36, 56, 59, 60]. The dot-probe task displays two stimuli side-by-
side, one depicting threat and one that is neutral. After the stimuli are removed, a target probe such as
an asterisk (e.g., “*”) appears in the same location as either the previously presented threat or neutral
stimulus. Participants are then asked to indicate the location of the target (e.g., left or right side of the
screen). Attention bias to threat is considered to be present if it takes an individual more time to draw
their attention away from the location of the threat than from the neutral stimulus in order to locate
the target. Anxious relative to non-anxious individuals (adults and children) tend to focus their atten-
tion toward threat stimuli to a greater extent and thus take longer to disengage from the location of the
threat stimulus when turning their attention to the target [53, 60]. Some work suggests that younger
versus older anxious individuals are more distracted by threat stimuli when other information demands
their attention [61]. Further, adolescents who were behaviorally inhibited in early childhood have also
shown heightened attention bias to threat, a bias further linked with social withdrawal [62]. However,
in some situations, extremely high levels of threat can lead the anxious individual to avoid rather than
linger their attentional focus on threat cues. Such patterns have been found both in adults exposed to
extreme life-stress and danger [63, 64] and in youth with anxiety disorders [35]. Such tendencies to
avoid acute threat appear to be transient in individuals studied in lower threat states [63, 65].
Neuroimaging techniques have been used to identify the neural substrates involved in attention
orienting and to examine differences in neural responses during attention orienting to threat between
youth with anxiety disorders and youth who are psychiatrically healthy. Key regions that have emerged
from these investigations include the amygdala and ventrolateral regions of the PFC. For example, in
one fMRI dot-probe study that used a relatively long period of exposure to threat stimuli (500 ms),
greater ventrolateral prefrontal cortex (vlPFC) activation was elicited in response to angry faces in
anxious relative to healthy adolescents; however, amygdala activation did not differ between the two
groups [35]. This pattern of vlPFC activity also correlated negatively with the severity of anxiety
symptoms, such that more vlPFC activity was associated with less severe anxiety.
Rodent studies suggest that activation of the amygdala is particularly relevant during the rapid
processing of threatening stimuli [15]. Thus, individual differences in the function of the amygdala
for anxious adolescents may be predicted specifically during brief stimulus presentations. To test this
hypothesis, a second fMRI study was conducted with the same dot-probe paradigm as described
above but with shorter (17 ms), masked exposures to threat [36]. In this second study, greater amygdala
activation occurred in response to angry faces in anxious than in healthy adolescents, and this pattern
of activation correlated positively with greater attention bias, as indexed by response time to the tar-
get, and the severity of anxiety symptoms. Together, the results from these two neuroimaging studies
with the dot-probe suggest that the duration of threat exposure modulates activation in different key
neural regions in anxious youth.
A third fMRI study used the dot-probe face emotion task to examine whether trait anxiety in a
sample of healthy children and adolescents would be associated with attention bias towards threat
[37]. As expected, trait anxiety was positively associated with an attention bias towards angry but not
happy faces. With regard to neural function, trait anxiety was positively related to right dorsolateral
PFC activation only to angry faces. In addition, trait anxiety was associated with greater vlPFC acti-
vation regardless of the valence of the face stimulus. Finally, with regard to genetic influences,
research has focused on a variant of the serotonin transporter (5-HTT) gene given its implications in
anxiety [66, 67]. Although patterns of anxiety and 5-HTT variations are somewhat mixed, lower lev-
els of 5-HTT are found among carriers of the short allele (S/S and/or S/L) relative to individuals with
two long alleles (L/L). Relative to L-allele carriers, healthy adolescents who are S-allele carriers
exhibit greater attentional bias to subliminally shown fear faces and greater response to fearful and
angry faces in the brain’s association cortex, an area implicated in attention control [68].
In sum, neural response patterns associated with attention orienting to threat show heightened
amygdala response in youth with anxiety relative to those without anxiety, particularly when rapid
processing of threat is required. Furthermore, greater amygdala responsivity also relates to more severe
anxiety symptoms, again in the context of processing threat cues in a brief amount of time. When the
time during which threat processing is lengthened, a different pattern emerges. Specifically, youth with
anxiety disorders relative to healthy youth show greater vlPFC response to threat with no amygdala
differences observed. Interestingly, among pediatric anxiety patients, those with the most severe anxi-
ety symptoms had lower vlPFC activity whereas patients with less severe impairment had greater
vlPFC activity. These patterns suggest that vlPFC response is not necessarily tied directly to anxiety
symptoms but might modulate activity in other regions, such as the amygdala, which is closely linked
to anxiety symptoms. Thus, the vlPFC could play a compensatory role by regulating and reducing per-
turbed function in the amygdala, particularly if it comes online further along in the sequence of reacting
to threat to regulate emotions and behaviors to allow for more strategic allocation of attention [9]. This
role would be consistent with higher vlPFC activity among anxiety patients with less severe function-
ing. Overall, vlPFC input may be recruited during longer exposures to threats to facilitate deeper, more
comprehensive processing whereas the amygdala serves as a rapid threat detector that is overly respon-
sive to immediate, even subconscious perceptions of threat, in anxious youth. As such, the vlPFC may
be recruited at different time points to help modulate emotional responses related to anxiety through
cognitive functions in order to inhibit behaviors or thoughts or to update rules or goals.
Threat Learning
The excessive fear responses to threat cues seen both behaviorally and physiologically in anxiety may
also arise from difficulties in learning to discriminate threat cues from safety cues, also known as
threat learning [69–71]. Threat learning involves correctly determining what cues and in which
situations indicate potential danger or safety. Fear conditioning paradigms have been used to assess
threat learning processes relevant to anxiety. In fear conditioning experiments, a neutral stimulus is
set to acquire a value signifying threat via repeated pairings with an aversive unconditioned stimulus
(UCS). Over time the UCS becomes a reinforced conditioned stimulus (CS+) (see Chap. 1 for further
discussion of fear learning). Perturbations in threat learning are seen in adults with high levels of anxi-
ety who show greater fear toward a CS+ than do adults with low levels of anxiety [72]. Anxious adults
also show greater fear toward non-reinforced conditioned stimuli (CS−) which are nonthreatening
cues that are not followed by the UCS [72]. This latter finding represents stimulus generalization
whereby the more similar a CS+ and a CS− are perceptually (e.g., hair color), which can be achieved
by morphing two different faces together incrementally until they overlap, the more anxious individu-
als respond to both stimulus classes with excessive fear [73, 74].
Research on threat learning in adults has set the stage for both behavioral and neuroimaging studies
of threat learning in pediatric anxiety. Behavioral studies have found that, relative to healthy children,
children with anxiety disorders show difficulty discriminating between CS+ and CS− cues and greater
arousal via skin conductance during fear conditioning, and stronger orienting and anticipatory sensi-
tivity to emotional valence during extinction [75, 76]. Evidence also suggests that children with anxi-
ety disorders experience a CS+ stimulus as more unpleasant than healthy children or children at
familial risk for anxiety disorders [75]. Other work has shown that even when both anxious and
healthy children similarly experience discriminative conditioning, children with anxiety relative to
healthy children show greater arousal (via larger skin conductance responses) to CS+ and CS− cues
during acquisition, report that the CS+ relative to the CS− cue is more arousing, and exhibit more
resistance to extinction as measured by skin conductance responses but not as measured by arousal
ratings to the CS+ versus the CS− cues [77]. Together, these studies indicate that anxious children
have greater difficulty discriminating between threat and safety cues and modulating their emotional
arousal and orientation to such cues and, subsequently, do not easily dissociate during extinction the
previously established connections between threat and neutral cues. These patterns suggest that pedi-
atric anxiety, as adult anxiety, is clearly associated with perturbations in the ability to make flexible
and adaptive associations between emotionally valenced cues and outcomes.
While behavior-based threat learning difficulties have been documented in anxious children
[75–77], less work has focused on assessing the neural correlates of threat learning difficulties in
pediatric anxiety. An experimental task has been developed recently using a UCS that maintains its
aversive meaning but remains appropriate for use with pediatric populations and lends itself to use
within a neuroimaging context. This task paradigm presents a fearful female face that is accompanied
by an extremely loud scream [70], two cues that imbue high biological and social salience. Presentations
of the aversive UCS (fearful female face + scream) are paired with a neutral face to probe condition-
ing and extinction to a neutral cue that becomes a threat cue (CS+). A second stimulus, novel neutral
face, is used as a safety cue since it is not presented with the UCS in order to assess generalization
from threat to safety cues (CS−). This fear conditioning paradigm has been tested in an fMRI study of
healthy adolescents and adults to ascertain typical neurodevelopmental correlates of threat learning
and to generate a baseline in healthy development against which the atypical pediatric anxious pattern
may be compared in the future [78]. Three key results emerged from this study. First, behavioral data
indicated weaker discrimination between threat and safety cues in adolescents than adults. Second,
adolescents relative to adults showed greater amygdala and hippocampus activation to CS+ versus
CS− conditions, indicating enhanced sensitivity of these early-maturing subcortical regions in younger
individuals when distinguishing between threat and safety cues [78]. Finally, adults relative to adoles-
cents showed a positive association between dorsolateral PFC (DLPFC) recruitment and fear ratings
when discriminating between threat and safety. Because prefrontal areas such as the DLPFC follow a
more protracted developmental course [79], enhanced engagement of the DLPFC in adults suggests
that it helps support making distinctions between relatively similar-looking cues to inform correct
categorization of stimuli. Overall, these neural data suggest age differences in the degree to which
subcortical and prefrontal regions are engaged during threat learning.
To date, the fear conditioning paradigm described above has only been studied behaviorally in
adolescents with anxiety disorders [70]. In this initial study, conditioning was established based on
higher ratings to the CS+ versus the CS−, but it did not vary as a function of anxiety diagnosis; thus,
all adolescents were more afraid of the threat than the safety cue. Pediatric anxiety was associated
with high levels of reported fear after conditioning, but the levels of fear were not associated with
greater discrimination between the classes of conditioning cues, rather they were associated with both
the CS− and the CS+ neutral faces. Future work will need to establish whether distinct neural corre-
lates are associated with these patterns of behavior in youth with anxiety disorders.
Taken together, the available work on the developmental course of threat learning and anxiety sug-
gest that the neurodevelopmental differences in subcortical and prefrontal brain responses during the
discrimination between threat and safety cues may play a role in the emergence of anxiety in child-
hood or adolescence and its maintenance into adulthood. In cases of immature prefrontal develop-
ment, flexibility in adapting to increased ambiguity may be compromised and lead to difficulties in
threat learning and a greater generalized fear response to threat and safety cues encountered in day-
to-day life. Future work should include longitudinal studies of large groups of similarly aged indi-
viduals at this developmental transition and follow them well into adulthood as well as compare them
to anxiety-disordered age mates.
Social–Emotional Information Processing
Moving beyond cognitive functions such as attention orienting and fear conditioning, the processing
of affect displayed by social cues and within different social contexts is another key, symptom-rele-
vant construct well represented in fMRI studies of pediatric anxiety. By targeting how the brain
responds to social–emotional information such as emotions displayed on faces, specific neural pat-
terns have emerged in relation to type of emotion, attentional focus, and stimulus class. For example,
during very specific instances of potential social evaluation, socially anxious adolescents react with
an exaggerated fear response even to positive smiling faces [45]. Moreover, as noted above, lesion
work in monkeys suggests that neural correlates of social–emotional information processing exhibit
unique developmental changes [27]. As such, it is particularly important to chart the neural correlates
of social threat processing in adolescents and adults. In the sections that follow, we review results
from neuroimaging studies of pediatric anxiety that involve either processing emotional faces or
responding to conditions of social evaluation or judgments.
Face Emotion Processing
Initial studies used facial expressions of emotions to probe whether patient groups with impaired
emotion processing and regulation would show aberrant neural responses to different facial emotions.
Fearful facial expressions have been particularly useful because of their ability to increase amygdala
activity, a region highly relevant to anxiety, even if an individual does not necessarily report feeling
fearful of such a face [80]. One reason for this threat-related response to fearful relative to angry faces
may be due to the ambiguity conveyed by a fearful face about the location of potential threat.
Furthermore, fearful faces are not encountered frequently in one’s environment, but when they are
present, they signal that there is a threat and the source of potential threat needs to be determined to
remain safe.
In the first functional neuroimaging study of children and adolescents (8–16 years old) with anxiety
disorders, higher levels of amygdala activity were found in response to simply viewing fearful faces
as compared to youth with no psychiatric disorders [38]. An additional comparison showed a blunted
amygdala response in a small group of depressed youth relative to anxious youth, suggesting that
increased amygdala response during fear processing is specific to anxiety disorders. Similarly, in
other work, greater amygdala response to fearful faces was associated with greater severity of daily
anxiety symptoms [38] as well as severity of social anxiety symptoms [39].
A series of neuroimaging studies in adolescents with anxiety disorders have also reported enhanced
amygdala response to fearful faces, particularly when anxious adolescents are asked to contemplate
how afraid they felt while looking at the faces [40, 42, 43]. In contrast, when asked to just view fearful
faces without monitoring emotional responses, both anxious adolescents [40] and those at tempera-
mental risk for anxiety [41] have shown reduced amygdala response to fearful relative to neutral faces,
a pattern that opposes that seen in healthy adolescents [81]. These studies suggest that attentional
focus matters in youth with anxiety insofar as it modulates amygdala response. One possibility is that
amygdala hyperactivation occurs when attention is drawn to the act of monitoring one’s feelings of
fear but not when attention is unconstrained. This could occur because anxious youth avert their atten-
tion away from the face to avoid a feared stimulus. When required to focus on the feared stimulus,
amygdala perturbation could reflect high sensitivity to processing subjectively experienced feelings
of fear in the anxious child.
Research on the genetic and developmental variations in amygdala response to fearful faces has
also started to emerge. These approaches are important because pediatric anxiety disorders strongly
predict adult anxiety disorders [1, 82, 83]. As such, for some individuals, the association between
anxiety disorders in early and later life may be shaped by genetic influences on the brain during criti-
cal developmental transitions such as from adolescence to adulthood. Thus, brain function may serve
as a potential intermediate phenotype worthy of attention for understanding the underpinnings of
adult anxiety.
To examine developmental mechanisms underlying associations between genetic influences on
brain responses to emotional stimuli and anxiety, Lau et al. [43] examined the effects of the 5-HTT
gene variant and diagnoses on amygdala response to emotional faces. While focused on internal feel-
ings of fear, healthy adolescents who were S/L carriers had greater amygdala activation than L/L
individuals, whereas L/L adolescents with anxiety or depression diagnoses showed greater amygdala
response than their S/L counterparts. While the effect of heightened amygdala response to fearful
faces found in healthy adolescents with the S/L allele was consistent with past findings in healthy
adults, the opposite effect of increased amygdala response to fearful faces in adolescent patients with
the L/L allele was contrary to past reports in adult patients [84]. The former result suggests that the
risk conveyed by the short allele 5-HTT gene variant may be conserved across development; however,
the latter result is harder to interpret as very few studies have examined gene–brain function relation-
ships in affected individuals (including youth or adults), and more work is needed to reconcile incon-
sistent results from these studies.
Given its role in affect dysregulation, research has targeted the Val, Met, and Val-Met polymor-
phisms of the human Brain Derived Neurotrophic Factor (BDNF) gene in adolescents with anxiety
and/or depressive disorders [85]. Results from this study found that Met-carriers showed greater
amygdala and hippocampal responses to emotional faces than Val/Val homozygotes among adoles-
cent patients relative to controls. Although preliminary, these new data from “imaging genetics” pedi-
atric studies suggest that a continued focus on brain function and genes may reveal vulnerability
mechanisms for anxiety across development.
Other work has taken a developmental approach to investigate potential vulnerability mechanisms
given the persistence and long-term risk that adolescent anxiety predicts for adult anxiety. In a recent
study, neural response to emotional facial expressions was compared between adults and adolescents
with social phobia [44]. Results from this study indicated greater activation in the amygdala and
rostral anterior cingulate cortex (rACC) in response to angry and fearful, but not neutral faces in both
adolescents and adults with social phobia. In adults but not adolescents, greater severity of social
phobia was also associated with greater rACC activation. Although these findings are cross-sectional,
the similar neural correlates in adolescent and adult social phobia suggest persistence in the neural
mechanisms underlying social phobia.
Social Evaluation Processing
A series of studies have used a type of face viewing task that simulates potential social evaluation, a
prominent experience for adolescents overall but also a main fear experienced by individuals with
social anxiety [45, 46, 86, 87]. The task used in these studies was designed to create a context for
measuring neural response while an adolescent anticipates receiving feedback from an unknown peer
and another context to assess their emotional and neural responses to actually receiving either positive
or neutral feedback. These constructs were selected specifically to give ecological validity to the neu-
roimaging task by mimicking adolescents’ daily life experiences but also to reflect core symptoms in
social anxiety.
With regard to the anticipation of peer feedback, as expected, greater amygdala activity was
observed among socially anxious versus healthy adolescents when judging how interested unknown
peers would be in chatting with them during a later interaction [45]. This was particularly evident
when viewing peers the adolescent had judged as being of low interest to them for an interaction.
Additional results from functional connectivity analyses showed that amygdala and vlPFC activations
were more strongly correlated in socially anxious adolescents than in healthy adolescents when antic-
ipating social evaluation from the negatively perceived peers. In addition to these findings in socially
anxious adolescents, data in typically developing adolescents reveal neural activation within key areas
implicated in affective processing (e.g., ventral striatum, hippocampus, insula, and hypothalamus)
that varies by age and sex [86]. Specifically, neural activation increased with age in older (14–17 years
old) relative to younger females (9–13 years old) but showed no association with age in males. These
developmentally based results suggest that vulnerabilities to anxiety problems may be more promi-
nent at certain ages for females. Thus, further work is clearly needed using this paradigm in healthy
and anxious children and adolescents of various ages and sexes.
Examination of adolescents’ emotional response to the receipt of peer feedback has yielded intrigu-
ing findings as well. Both healthy adolescents and those with social anxiety showed activation in the
amygdala–hippocampal complex just prior to receiving positive or negative peer feedback relative to
baseline [46]. However, after being rejected by peers, anxious relative to healthy adolescents showed
persistent amygdala–hippocampal activation, whereas the healthy adolescents showed reductions in
amygdala activity once they received negative feedback. This poor neural recovery from a negative
emotional experience seen in adolescent anxiety may relate to problems with inhibiting amygdala
response or with regulation of amygdala sensitivity [88, 89]. Though not directly examined in this
study, these anxiety-related neural perturbations may be associated with greater cognitive distortions
about emotional events, which, in turn, may result from the imbalance between cognitive and affective
processing during the adolescent period [18, 90].
Finally, another form of social interaction and evaluation that has been examined in conjunction
with fMRI involves the Prisoner’s Dilemma game in which participants must choose to cooperate or
betray a co-player in an attempt to earn as much money as possible. Behaviorally, anxious adolescents
were more likely than healthy adolescents to maintain positive interactions when possible through
cooperation with co-players, particularly after a co-player chose to betray the participant [47]. FMRI
data showed increased activation in the anterior precuneus and right temporal parietal junction
among anxious versus healthy adolescents but increased medial PFC and ACC activation in healthy
relative to anxious adolescents [47]. These results suggest that anxious youth exhibit a heightened
tendency to engage in increased self-focus and may also tend to ruminate about their behaviors during
interpersonal interactions which manifests in altered brain function. Overall, these studies provide
important clues to cognitive and emotional processing of social stimuli in health and anxiety [18].
Reward Processing
Across the processes involving attention orienting, threat learning, and social–emotional information
processing, the repeated findings of abnormal amygdala function suggest that anxious adolescents are
readily influenced by threatening cues; in turn, this set of processes may compromise emotion regula-
tion and perpetuate chronic, extreme anxiety. While the amygdala clearly processes social threat,
research on social–emotional development in primates suggests that structures beyond the amygdala
are likely to play equally important roles in facilitating response to social threats. For example, findings
of enhanced social fear in juvenile primates without a functioning amygdala demonstrate that social
fears in juveniles must also be instantiated in neural circuitry that extends beyond the amygdala [91,
92]. Moreover, given that removal of the amygdala heightens social fears, components of the circuitry
mediating response to social threats are likely to be involved in feedback loops with the amygdala.
Although most work on social fears and anxiety in humans examines amygdala function, these data
in nonhuman primates highlight the need to examine other structures early in development.
Beyond the amygdala, another key subcortical structure that has recently been investigated in rela-
tion to pediatric anxiety is the striatum. The striatum generally includes the nucleus accumbens, cau-
date, and putamen and encompasses a ventral and dorsal area, with strong connections to frontal
cortical regions, the hippocampus, and the amygdala [93, 94]. The striatum is involved in associating
emotionally salient environmental stimuli with anticipated outcomes to guide approach or avoidance
behavioral responses [93, 95]. As such, striatal circuitry has been well characterized in research on
substance abuse and addiction [96, 97]. Extensions of the addiction literature have focused on striatal
function with other classes of motivationally salient stimuli, namely, rewards and punishments.
New discoveries have emerged in our understanding of reward processing in anxiety with the use
of monetary incentive cues that highlight how incentives modulate approach and avoidance behaviors
[98, 99]. A focus on neural correlates of reward processing in pediatric anxiety grew out of initial
work on behavioral inhibition, an early-life temperament style that carries increased risk for later
anxiety, especially social anxiety [100, 101]. One of the first neuroimaging studies in this area docu-
mented heightened sensitivity in the striatum to anticipated incentives [48]. Specifically, adolescents
whose temperament had been characterized in early childhood as behaviorally inhibited showed
increased striatal response as the magnitude of the incentive increased; adolescents not characterized
as behaviorally inhibited did not show this modulation by incentive value. One possible explanation
for this pattern is that striatal dysfunction may reflect anxiety during anticipation of uncertain out-
comes or concern over performance when the stakes increase. Indeed, follow-up studies showed
increased striatal activation in adolescents characterized by early-childhood behavioral inhibition
relative to their non-inhibited counterparts when receipt of anticipated incentives was contingent on
one’s actions [50] and when anticipated incentives were not actually provided [51].
The early-childhood behavioral inhibition findings described above suggest that sensitivity of the
striatum may be a neural marker in addition to amygdala sensitivity [41, 102] that links early-child-
hood behavioral inhibition specifically to later anxiety. Indeed, both social phobia and social subordi-
nation, which shares behavioral features of social phobia, are associated with dysfunctions in the
striatal dopaminergic system [103–106] and altered striatal function [107]. Thus, identifying altera-
tions in striatal function during anticipatory performance-based or social situations could reveal
pathophysiological traits common to both social phobia and behavioral inhibition. Recent work
confirmed this hypothesis by showing striatal hypersensitivity to anticipated incentives in adolescents
with SoPh but not GAD [52]. It may be that striatal function is a biomarker that differentiates between
these two anxiety diagnoses while the amygdala is involved in anxiety in a nonspecific fashion
that does not differentiate between the anxiety disorders. Moreover, the findings in socially anxious
adolescents closely resemble those in children with behavioral inhibition. As such, adolescents with
social phobia and adolescents with early-life behavioral inhibition show similar patterns in certain
striatal regions during reward processing which indicates the importance of considering more than
one affectively relevant neural system as well as additional psychological processes in pediatric
anxiety.
Related to reward processing and anticipating outcomes, intolerance to uncertainty is a trait associ-
ated with anxiety, extreme worry, and impaired decision-making. In a study of adolescents with GAD
or SoPh, the relationship between intolerance to uncertainty and neural responses to uncertainty was
examined [49]. High levels of intolerance to uncertainty were associated with increased activation in
frontal and limbic regions including the anterior cingulate cortex, orbitofrontal cortex, and amygdala
in response to uncertainty during a decision-making task. Intolerance of uncertainty emerged as a
cognitive trait associated with neural regions that may contribute to the maintenance of pediatric anxi-
ety disorders. These results also highlight the variability related to trait characteristics that exist within
adolescents with anxiety disorders and suggest that using such an approach for characterization of
pediatric anxiety may prove fruitful in tailoring treatments to subgroups of patients depending on their
profiles of key traits and neural response patterns.
Functional Connectivity in Pediatric Anxiety
Recently, studies have begun to examine functional connectivity in the context of anxiety disorders.
Typically, the goal of studies examining functional connectivity is to determine the degree of co-
activation among various brain regions. Functional connectivity can be measured during two condi-
tions: (1) a specific task (task-dependent functional connectivity or TDFC), typically one related to
emotion salience or emotion regulation in the case of anxiety disorders (i.e., how does activity in one
region relate to or “regulate” activity in another region during different task-related events), or (2) a
state of rest (resting state functional connectivity or RSFC) when the individual is not engaged in any
particular assigned task (i.e., what neural interactions occur spontaneously while an individual has
their eyes closed or is fixating on a cross). While measuring either TDFC or RSFC, the co-activations
of regions within a particular known neural network may be investigated. Or, alternatively, a specific
“seed” region may be identified so that the degree of covariation between activity in this seed region
and activity in other regions may be measured, which can lead to the identification of new interrelated
networks.
Task-Dependent Functional Connectivity
Among the handful of studies that have examined patterns of TDFC in patients with anxiety disor-
ders versus controls, connections have been examined across a range of neural networks. Adults with
anxiety disorders exhibit stronger connections between limbic regions (i.e., anterior insula) and
frontal and parietal regions [108], as well as weaker TDFC within prefrontal networks [109] and
within superior temporal networks [110]. Despite this range of findings, however, the majority of
work on this topic has focused largely on links between subcortical/limbic regions (responsible for
processing salience and affect) and cortical/frontal regions (responsible for control or regulation of
affect and implicit drives). This is likely because an imbalance in the functioning of these regions
(e.g., hyperactivation of the amygdala combined with hypoactivation of the medial and lateral
prefrontal cortices) is often thought to characterize anxiety disorders, as discussed in other sections
of this chapter and recent reviews [111–113]. For example, one recent study of adults examined a
specific type of emotion regulation during reappraisal of negative self-beliefs—one of the hallmark
characteristics of social phobia. Results indicated less TDFC between the prefrontal cortex and the
amygdala among patients with SoPh versus controls [114], consistent with the notion that patients
are less able to regulate amygdala responses to negative emotions. Similarly, other work examining
patients with GAD has shown a similar pattern such that patients fail to engage regulatory regions in
response to heightened displays of amygdala activity resulting from emotional stimuli [115].
A small number of studies have examined functional connectivity in pediatric samples. Similar to
the work described in adults, one study found that compared to healthy controls, adolescents with
GAD displayed a relatively weaker negative TDFC between the lateral prefrontal cortices and the
amygdala during an emotional attention orienting task [36], which is consistent with the notion that
individuals with anxiety are less able to regulate neural responses to emotion, even prior to adulthood.
Interestingly, however, another study that examined pediatric patients with social anxiety disorders
found a somewhat different pattern of results. Specifically, socially anxious patients displayed stron-
ger positive TDFC between the lateral prefrontal regions and the amygdala during the anticipation of
social evaluation by peers than healthy controls who showed relatively little TDFC [45]. While more
research will help clarify these patterns of results, it is possible that the distinct processes that are
involved in responding to negatively valenced stimuli (i.e., anticipating, versus actually responding to,
a negative stimulus) may be characterized by distinct patterns of TDFC in anxious individuals.
Resting State Functional Connectivity
In studies of clinical populations, RSFC may be a particularly useful way of studying neural interac-
tions for several reasons [116–118]. First, RSFC analyses permit investigators to examine patterns of
intrinsic functional connectivity underlying different, simultaneous functions. Thus, there is less need
to isolate a particular construct of interest using a specific task. Second, when examining brain activ-
ity while individuals are resting, biases among particular clinical populations in terms of how they
interpret task instructions or respond to certain stimuli will be significantly reduced. Thus, these
biases will be less likely to produce group differences that are solely task dependent. Third, examining
resting brain activity increases the probability of enrolling patients in studies who have a limited abil-
ity to comply with certain task demands. In other words, studies of RSFC may permit the inclusion of
individuals who are more impaired than those typically included in clinical neuroimaging studies.
Finally, given that RSFC is not task dependent, there is greater reliability across research sites and
scanners, which facilitates the study of larger samples [119]. This is particularly important for studies
of pediatric anxiety disorders that often suffer from small sample sizes.
Similar to the TDFC studies described above, most of the RSFC studies examining neural function
in relation to anxiety disorders have found results that are consistent with the notion that anxiety dis-
orders may be characterized by dysregulation between frontal and limbic networks, resulting in an
inability to regulate responses to emotional events [111–113]. Here we briefly discuss some of the
RSFC studies most relevant for understanding limbic/frontal connections in the context of anxiety
disorders, given that this has been the focus of the majority of this work thus far. Moreover, it is worth
noting that studies examining RSFC have so far focused exclusively on adult populations; neverthe-
less, we review them here because of their potential relevance for exploring pediatric populations in
future research.
First, a few studies have specifically focused on SoPh. One of these studies found that the amygdala
showed reduced RSFC with two regions commonly linked with higher-level control processing, both
the medial orbitofrontal cortex and the portion of the medial posterior parietal cortex that includes
both the posterior cingulate cortex and the precuneus [120]. The connectivity between these regions
was particularly reduced among individuals with higher state anxiety. Similarly, another study found
that adults with SoPh show reduced RSFC between the amygdala and the inferior temporal gyrus and
increased RSFC between the amygdala and occipital regions [121]. This is consistent with the com-
monly reported finding that individuals with SoPh have exaggerated affective responses to visually
observed stimuli combined with an inability to properly regulate these affective responses which
likely contributes to their heightened anxiety in social situations. Other work has further demonstrated
irregularities in the RSFC of several brain systems among individuals with SoPh, including altered
connections between limbic/subcortical and frontal/cortical networks [122, 123], as well as disrupted
connectivity within different regions of the frontal lobe, and between frontal and visual networks
[124]. Moreover, many of these findings have also been associated with the degree of patients’ symp-
tom severity [122, 124].
Results from a recent study of adults with GAD indicate increased RSFC between the amygdala
and a frontoparietal control network and decreased RSFC between the amygdala and regions linked
with stimulus salience, including the insula and the cingulate, as compared to healthy comparisons
[125]. At first glance, this finding seems to run counter to the idea that anxious individuals have
weaker neural connections between limbic/subcortical regions and control/frontal regions (as well as
heightened connections within the salience/affective network). However, the authors suggest a com-
pensatory role of the frontoparietal network and suggest that heightened connectivity between limbic
and control regions may reflect additional regulatory resources needed to compensate for the height-
ened affective responses that typify this population. Liao and colleagues [123] also propose a com-
pensatory model in which cortical regions are more strongly connected with limbic regions among
individuals with SoPh; however, it is not yet clear when compensatory models might be most relevant
(i.e., compared to models focusing on the hyperactivation of limbic regions and the hypoactivation of
control regions). In fact, the results from another recent study examining RSFC in healthy individuals
did not appear to be consistent with this compensatory model. Specifically, this study demonstrated
that healthy individuals who reported high levels of anxiety showed negative correlations between
activity in the amygdala and ventromedial prefrontal cortex during rest whereas those who reported
low levels of anxiety showed positively correlated activity [126]. High anxious individuals also
showed uncorrelated activity in the amygdala and dorsomedial prefrontal cortex while low anxious
individuals showed negatively correlated activity. One additional study has shown heightened state
activity during an off-task period after an initial task involving worrying among individuals with GAD
in both limbic (i.e., the anterior cingulate cortex) and frontal (i.e., the dorsomedial prefrontal cortex)
regions [127], which implies that those with GAD continue to worry; however, this study did not
examine functional connectivity. Thus, additional research will be helpful in better elucidating irregu-
larities of neural connectivity among individuals suffering from anxiety disorders.
Resting state EEG has also been used to assess underlying functional connections across the brain
related to anxiety. These studies focus on the relationship between slow and fast waveform activity,
which is believed to index the functional connectivity between subcortical/limbic regions and corti-
cal/frontal regions. Thus, the relationship between slow and fast activity may reflect patterns of inhib-
itory control over motivational goals [128]. To our knowledge, EEG investigations of RSFC have not
been carried out in clinically anxious populations; however, two recent studies examined aspects of
anxious functioning among healthy individuals. One study demonstrated that healthy individuals
with higher ratings of anxiety displayed EEG recordings consistent with weaker connectivity (i.e., a
higher ratio between slow and fast waveforms) between frontal and limbic regions [129]. A second
study provided evidence that resting state EEG activity among individuals displaying greater anxiety-
related threat biases (i.e., avoidance of threatening stimulus displays) was similarly indicative of a
weaker cortical/limbic connection [130]. Thus, together these studies are consistent with data from
fMRI research indicating that individuals with greater anxiety may have reduced frontal control over
affective processes.
Treatment of Pediatric Anxiety: Implications for the Brain
The field of clinical cognitive neuroscience has been moving in an exciting direction by examining
clinically relevant cognitions, emotions, and behaviors that characterize anxiety and relate to impaired
functioning. This approach offers the potential for conceptualizing and pinpointing ways in which
cognitions, emotions, and behaviors could be targeted in interventions for pediatric anxiety such as
CBT or pharmacological interventions (e.g., SSRIs), both of which are very effective for treating
anxiety [131–138]. For example, CBT offers patients tools such as cognitive reframing and self-
monitoring to gain control over their symptoms. The well-documented pattern of amygdala hyperac-
tivation in pediatric anxiety elicited during a range of psychological processes (e.g., face emotion
processing, attentional bias) represents a possible biological marker for targeted intervention efforts.
Indeed, emerging evidence suggests some potential pathways for intervening that are guided by
knowledge of the pathophysiology of anxiety and relate to treatment response. The application of
neuroimaging to testing treatment-related changes in brain function is relatively new, but there are
some intriguing patterns emerging from the existing literature.
One study, which used the same face emotion task described earlier to assess fearful face process-
ing, found that greater pretreatment amygdala activation in pediatric anxiety-disordered patients was
associated with better response to both CBT and pharmacological treatments [139]. Amygdala hyper-
activation was specific to conditions during which patients attended to their internally experience fear
of salient emotional faces. Furthermore, both a decrease in symptoms across treatment course and
posttreatment anxiety symptom severity were associated with this pattern. Nonetheless, it is important
to consider that the documented amygdala perturbations may be present in a portion of pediatric anxi-
ety cases that respond effectively to CBT or psychopharmacological treatment, whereas other cases
who are more treatment resistant may react more positively to treatments that elicit input from other
brain regions.
Another study focused on treatment-related brain response changes in association with attention
orienting using a dot-probe task. Here, adolescents with GAD exhibited a significant increase in right
vlPFC activation in response to angry versus neutral faces following effective treatment with either
CBT or an SSRI [140]. As in past neuroimaging results comparing pediatric anxiety patients and
controls, these treatment-related results also suggest the vlPFC may facilitate effective neural and
affective responding via other brain regions (e.g., amygdala), perhaps through regulating overwhelm-
ing emotions or reframing biased cognitions. Thus, targeting the ventral regions of the PFC may offer
one mechanism by which negative emotions such as anxiety can be reduced.
Striatal responses to reward have also been examined in the context of treatment for adolescent
depression [141]. In this study, a monetary reward task was administered to assess striatal response
during the anticipation of reward outcomes prior to the start of 8-week open label treatment with
either CBT or CBT plus an SSRI. During each of the eight weeks of treatment, clinician ratings of
symptom severity and improvement and self-reported anxiety and depressive symptoms were
obtained. Greater pre-treatment striatal response to reward anticipation was associated with lower
clinician-rated severity and lower anxiety symptom levels after the course of treatment. Interestingly,
greater striatal response was associated with a faster reduction in anxiety symptom levels. These
results suggest that a typical striatal response (increased rather than reduced as seen in depression)
is associated with a better response to treatment, in terms of anxiety symptoms. It also suggests a
role of anxiety in the reward-related pathophysiology of adolescent depression, which underscores

recent findings showing elevated striatal response to monetary incentives in adolescents with
diagnosed anxiety disorders [52].
Conclusions and Future Directions
Clinical cognitive neuroscience provides an exciting bridge between basic and clinical domains of
psychiatric and psychological research, particularly in the area of anxiety. Our current understanding
of brain-behavior relationships is possible because of the applicability of animal models of fear
responses to humans. As this chapter described, neurobiological research using tools such as fMRI
has allowed for the testing of hypotheses about how specific neural circuits underlie psychological
processes that shape behavior. Adding a developmental component to this approach has further deep-
ened our understanding of the nature of neural structures and circuits and their connections in relation
to pediatric anxiety.
Future work in this area will benefit from the inclusion of larger samples as well as of pure patient
groups for cross-comparisons where possible. In addition, although the normative, longitudinal pro-
gression of brain structure has been fairly well characterized [21, 28, 79, 142–144], studies mapping
longitudinal trajectories of brain function in response to the types of tasks described in this chapter
need to be conducted in both pediatric health and anxiety. It would also be beneficial to chart longitu-
dinal changes in anatomy among anxiety-disordered youth to pinpoint whether anxiety has long-term
influences on neural structures such as the amygdala, striatum, or vPFC or whether these structures
drive anxiety over time. More research that employs techniques such as diffusion tensor imaging
would be beneficial for understanding anatomical connections within pediatric anxiety samples as
well as work that focuses on the relationships between function and structure. Finally, additional work
is necessary to determine the stability of neural functional change due to the effects of treatment once
it has been completed.
In sum, we have described work that aims to pinpoint what psychological processes are at play in
modulating and mapping neural structure and function in clinical pediatric anxiety. We hope that in
the next generation of research of this kind, the information gathered to date will be translated into the
development of effective, targeted treatments for pediatric anxiety.
Acknowledgements Support for this work was provided by the National Institute of Mental Health Intramural
Research Program and National Institutes of Health Career Development Award K99/R900 MH080076 to A.E.G. The
authors wish to thank Jennifer Buser and Sarah Ruiz for assistance with literature reviews and table and figure creation.
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Temperamental Risk Factors for Pediatric
Anxiety Disorders
Kristin A. Buss and Elizabeth J. Kiel
Abstract Fearful temperament, most often conceptualized as behavioral inhibition, has been found to
be a robust predictor for the development of pediatric anxiety disorders, with most evidence suggesting
a link with social anxiety disorder. In addition to a detailed review of behavioral inhibition, recent
work that supports a new construct, dysregulated fear, is also reviewed in this chapter. New evidence
is presented that demonstrates that dysregulated fear is conceptually and methodologically distinct
from behavioral inhibition and improves the prediction of which fearful toddlers are at risk for pedi-
atric anxiety disorders. The following review will summarize the empirical bases for these two
approaches and their role in the development of anxiety disorders, as well as evidence for biomarkers,
executive processes, and parenting environment that exacerbate or ameliorate this early temperament
risk. Specifically, research on fearful temperament has identified multiple trajectories and outcomes
for children with the same underlying temperamental biases. That is, not all young children who
display fearful temperament maintain this behavioral profile or develop anxiety symptoms. Therefore,
this chapter summarizes evidence for biological, regulatory, and parental processes that account for
these divergent trajectories and addresses the question of which fearful children are at highest risk for
developing anxiety disorders.
Keywords Fearful temperament • Behavioral inhibition • Dysregulated fear • Maternal overprotection

• Pediatric anxiety disorders • Development • Biomarkers • Executive processes
Over the past 25 years, a great deal of research has focused on fearful temperament as a putative risk
factor for the development of pediatric anxiety disorders, with most evidence suggesting a link with
social anxiety disorder [1–8]. The bulk of the literature on fearful temperament has been framed by
the prominent approach of behavioral inhibition; thus, this will be discussed in detail in this chapter.
However, we also include recent work that supports a new construct, dysregulated fear, which is
conceptually and methodologically distinct from behavioral inhibition and improves the prediction
of which fearful toddlers are at risk for pediatric anxiety disorders [9]. The following review will
summarize the empirical bases for these two approaches and their role in the development of anxiety
disorders, as well as evidence for biomarkers, executive processes, and parenting environment that
K.A. Buss (*)

Department of Psychology, The Pennsylvania State University, University Park, PA, USA
e-mail: kab37@psu.edu
E.J. Kiel
Psychology Department, Miami University, Oxford, OH, USA
48 K.A. Buss and E.J. Kiel
exacerbate or ameliorate this early temperament risk. Throughout this chapter, the broader term of
fearful temperament will be used if neither behavioral inhibition nor dysregulated fear is specified.
Research on fearful temperament has been influenced by two theoretical traditions in developmental
science: temperament theory and developmental psychopathology. Most researchers agree that tem-
perament refers to individual differences in behavioral tendencies that appear in infancy, are relatively
stable across the lifespan and across situations, and involve biological and heritable underpinnings
[10, 11]. More specifically, dimensions of temperament reflect individual differences in the reactivity
and regulation of behavioral and biological expressions of basic affective processes, such as fear [12, 13].
Given the complexity of temperamental variation, no single measure of behavior is believed sufficient
to characterize these individual differences. Thus, it is best captured by measuring several response
parameters such as behavioral frequency, intensity, and duration of responses across multiple con-
texts, raters, and systems of response (e.g., behavioral and biological) [12, 14, 15]. Unlike other
temperament constructs or dimensions (e.g., activity level, positivity), research on fearful tempera-
ment has always focused on integrating across multiple systems, helping to push the temperament
field into an ever-growing interdisciplinary science, for instance, with the integration of biological
measures [16, 17].
Despite theoretical emphasis on the stability of temperament traits, work on fearful temperament
has identified multiple trajectories and outcomes for children with the same underlying temperamen-
tal biases. That is, not all young children who display fearful temperament maintain this behavioral
profile or develop anxiety symptoms [1–8]. The developmental psychopathology perspective acknowl-
edges this complexity, emphasizing the interaction between a child and the environment that influences
adaptive and maladaptive developmental trajectories [18–20]. For instance, deviations from normal
development that put a child at risk for anxiety may exist not only in individual characteristics of the
temperamentally fearful child but also in relationship factors (e.g., parenting) that disrupt the achieve-
ment of age-related tasks [6]. In line with the developmental psychopathology perspective, it is also
possible that, in addition to risk for developing classifiable disorders, temperamentally fearful children
may show failures in typical developmental tasks or adaptation at important milestones, such as
the transition to kindergarten, that would increase their risk for later disorder [19, 21]. For example,
temperamentally fearful children are likely to exhibit social withdrawal [22–24] and lack of peer
competence [25, 26], which interfere with the formation of friendships and perhaps lead to peer rejection.
These social vulnerabilities may put children at increased risk for later social anxiety disorder and
other internalizing symptoms.
Before proceeding, some discussion of conceptual and methodological issues is warranted in order
to interpret the predictive validity of early temperamental fearfulness on the development of anxiety
disorders. A nontrivial amount of conceptual and methodological overlap exists in the broader litera-
ture on fearful temperament and in the literature on social wariness (e.g., shyness, reticence). Whether
behavioral inhibition, dysregulated fear, social withdrawal, anxious solitude, shyness, and social anxi-
ety are different manifestations of the same underlying temperamental bias, partially overlapping
constructs that just differ in how and when they are measured, or orthogonal constructs remains an
open question in the literature. It is important to point out that extreme fearful temperament and social
withdrawal share common features such as avoidance of novelty, fearfulness, and physiological and
neural activity profiles [27, 28]. Much of this overlap may be an artifact of similar assessment methods
as all of these constructs can be objectively observed [29]. However, they can also be distinguished
[28]. For instance, behavioral inhibition is characterized as fearful/wary behavior to novelty, while
social withdrawal is typically in response to familiar social situations (i.e., with peers), and anxiety
symptoms and diagnosis require subjective reports of distress. Another issue to consider is that varia-
tion in fearful temperament, especially in observational contexts, is more readily assessed in infants
and toddlers, and it is ever more challenging to attribute variation in inhibited or withdrawn behavior
solely to temperamental characteristics as children develop and encounter an ever-expanding social
network.
Temperamental Risk Factors for Pediatric Anxiety Disorders 49
Overview of the Fearful Temperament Literature
In this section, we review the literature on fearful temperament, with specific focus on the constructs
of behavioral inhibition and dysregulated fear. Given the specific goals of this chapter to present a
broad overview of the role of fearful temperament in the development of pediatric anxiety problems,
the current review of behavioral inhibition will not be as comprehensive as other published reviews
(see [30–32]).
Behavioral Inhibition
There are a variety of conceptualizations of fearful and extremely shy behavior in the temperament
literature including treating fear as synonymous with other types of negative affectivity [33], fear as
one component of a higher-order factor of negative affect [34, 35], fear as multidimensional with
distinctions between object fear and social fear [36], and fear as shy behavior manifesting in peer
interactions [22]. However, the approach forwarded by Kagan has received the most attention. Strongly
rooted in biological perspectives on individual differences, Kagan’s approach to temperament high-
lights qualitatively distinct types. This pioneering work began with observations of toddlers (~14–24
months of age) in a series of novel situations such as playing with a robot and adult stranger interactions.
Behaviors coded across these episodes were used to differentiate two temperament types: inhibited
children who were characteristically shy, fearful, and withdrawn, and showed signs of decreased
activity and approach [37–40], and uninhibited children who were characteristically bold showing
high activity and approach in these same situations. Identification of these two distinct groups has
been replicated across several different samples and laboratories [37–42]. In addition, studies have
examined behavioral inhibition characterized by similar sets of behaviors using a continuous composite
of fear behavior rather than a dichotomous group approach [1, 43–45].
These patterns of inhibited and uninhibited behavior have been predicted from reactivity to stimuli
early in infancy, supporting a biological and/or genetic basis. At 4 months, infants were exposed to a
variety of mobiles and other sensory experiences [46]. Four types of reactivity groups were created
based on infants’ responses to these stimuli: high motor–high cry, high motor–low cry, low motor–low
cry, and low motor–high cry. Infants who displayed high-motor and high-cry behavior in response to
the stimuli were labeled high reactive, while infants displaying low-motor and low-cry behavior were
labeled low reactive. Two years later, the high and low reactivity profiles predicted inhibited and unin-
hibited behavior, respectively [43, 46]. These infant profiles, their association with later toddler behavior,
and longitudinal outcomes have been replicated across other samples [43, 47–53].
The stability of behavioral inhibition has been well documented [1, 37–39, 43–53]. This has been
demonstrated in longitudinal studies of behavioral inhibition across the lifespan [15, 32, 46] including
development of social wariness later in childhood (see [31] for detailed review) [37–39, 49]. Despite
this consistency in reported stability, it is important to note that stability of behavioral inhibition is
fairly modest with not all inhibited children retaining their inhibited status across development or
becoming socially wary. In particular, some studies have reported stability for only a subset of children,
such as those who were most extreme in their behavior [42, 52, 53]. This observed instability may be
due to several factors. First, measuring behavioral expression of the same construct at different devel-
opmental periods can be difficult (i.e., heterotypic continuity). Second, the observed lack of stability
may be an artifact of attempting to aggregate across different developmental pathways of fearful children.
Most studies have used statistical approaches that examine linear predictions and focus on between-
person differences rather than focusing on within-person stability and nonlinear models of change
[54–57]. Third, across studies, indices of inhibition or fearful temperament may differ. Thus, it cannot
be assumed that any two groups of temperamentally fearful children are the same. Further, each of
these indices of “fear” may have unique associations with physiology and risk for anxiety symptoms
[58–61]. As a result, this heterogeneity in identification of behavioral inhibition may limit the ability
to accurately predict stability.
Despite these limitations in understanding the stability of behavioral inhibition, there is significant
evidence suggesting that children who are behaviorally inhibited are particularly at risk for social
withdrawal (e.g., reticent behavior with peers) [27, 49] and the development of social anxiety symptoms
in middle childhood [3, 62–66]. Children who show the most stable inhibition throughout childhood
appear to be at greatest risk for developing anxiety disorders in adolescence, particularly social anxiety
disorder [8, 32]. In light of evidence that social anxiety may be a mechanism by which fearful tem-
perament is linked to other anxiety and internalizing disorders (e.g., generalized anxiety disorder,
depression) [5, 21, 32, 64–68], middle childhood is a key period to examine the development of social
anxiety among extremely fearful or inhibited children.
Dysregulated Fear
Now we turn to discussion of the dysregulated fear construct, which is a new advance in the identification
of fearful children that builds upon the behavioral inhibition tradition. Individual differences in behav-
ioral inhibition are most often identified by aggregating (i.e., averaging) behavioral measures across
situations. Thus, the consistency in behavior across situations is the hallmark of characterizing children
as fearful/inhibited. However, upon closer examination of the correlations across situations, the behav-
ioral indicators of inhibition are only modestly correlated and low in many cases [9, 37]. Thus, it can
be argued that simply averaging behavior across multiple situations is not enough to capture the
complexity of fear because it obscures meaningful individual differences and may cause us to miss
children who show extreme fear only in specific contexts [9]. Based on this, the dysregulated fear
theory postulates that it is not only how much fear is exhibited but also when and what type of fear is
exhibited that is critical to identifying a more homogeneous pattern of behavior [9]. This is consistent
with other literature that suggests that expression of behavior with respect to the eliciting context may
be a key feature of individual differences in emotion regulation [67, 68], specifically anxious behavior
[69, 70]. Moreover, levels of distress that are not predictably matched to a situation (i.e., being fearful
in typically safe situations) are a key defining feature of most of the anxiety disorders. Thus, dysregu-
lated fear has been defined as behavioral responses that are not matched to the incentive properties of
the eliciting context or the availability of coping resources (e.g., high fear in low-threat, controllable
contexts). It was hypothesized that focusing on fear responses in low-threat situations would yield a
more homogeneous type of fearful child that would be empirically distinct from behaviorally inhib-
ited children.
In an initial study of this construct [59], 24-month-old toddlers participated in three versions of
a male stranger approach episode that varied in level of threat: (1) toddler was playing on the floor
with toys (least threatening), (2) toddler was sitting in a highchair, and (3) toddler was in a highchair
and cardiac physiology was recorded (most threatening). As predicted, mean levels of fear behaviors
(e.g., facial fear, distress), and duration of freezing in particular, varied across the three versions with
the toy play version of the stranger approach resulting in less fear and freezing compared to the other
versions. More interesting, however, was the identification of a group of toddlers who displayed long
durations of freezing behavior in the putatively lowest-threat situation (toy play version). These toddlers
had the highest cortisol levels and more sympathetic cardiac reactivity at baseline [measured by
pre-ejection period (PEP); see later section of this chapter for more detail on this work]. These data
Fear Levels as a Function of Threat

Level
90.00
Proportion of Fear Behavior Observed

Series1
80.00
Series2
70.00
Series3
60.00
Series4
50.00
Series5
40.00
Series6
30.00
Series7
20.00 Series8
10.00 Series9
0.00 Series10
Low Moderate High
Fig. 1 Graph of ten randomly selected cases from age 2 observational data. The proportion of time fear was observed
is plotted against the level of threat of the episodes. Cases appearing with square markers at data points represent
examples of dysregulated fear patterns, high fear in low-threat situations relative to high-threat situations; cases without
markers represent the typical fear pattern of increasing fear as threat increases
suggested that displaying high levels of fear in situations observed to be nonthreatening for most
children may reflect a type of dysregulation of fear that would put children at risk for a variety of
negative outcomes. Specifically, this approach to the characterization of fearful temperament had
potential to improve our prediction of which children are most at risk for developing anxiety [59].
A subsequent longitudinal study was conducted to replicate and extend these original findings [51].
Toddlers (24 months old) participated in six episodes all designed to be novel, either engaging or fear
eliciting and varying putatively in threat level [71, 72]. Two episodes were engaging and low in threat:
playing games with two friendly puppets behind a puppet theater and a female clown with a bag
of toys. Two episodes were designed to capture fear of strangers and to be moderately threatening:
one involving an interaction with a male stranger and one with a female stranger doing paperwork in
the corner of the room. Finally, two episodes were designed to be high in threat and novelty: these
involved a remote-controlled robot that lit up, made noises, and moved around on a platform and a
remote-controlled spider (i.e., toy spider placed on a hidden vehicle) that moved toward the toddlers.
The episodes used are largely similar but expand on those previously used to measure behavioral
inhibition, with the important addition of the low-threat episodes. In the first cohort, episode order was
counterbalanced in order to investigate differences in fear behavior as a function of episode type.
Based on a composite of several different behaviors indicating fear (e.g., facial fear, freezing,
proximity to mother), the average duration of fearful behavior increased as level of threat increased
with the lowest duration of fear behavior exhibited during the puppet show and clown conditions and
the highest during the robot and spider episodes [9]. Multilevel modeling was used to capture indi-
vidual patterns of change in fear from low to high threat, creating a slope measure for each toddler.
What is particularly relevant to a fearful temperament perspective is that significant variability in
these slopes was identified. For example, Fig. 1 shows plots of several cases showing different pat-
terns of fear across the three levels of threat. The typical pattern is characterized by the highest levels
of fear observed during the higher-threat episodes. In contrast, there are a few children who show
higher or equivalent levels of fear to the low- and high-threat contexts (lines marked with squares).
It is this pattern that we label dysregulated. Moreover, there was evidence that the toddlers showing
the highest levels of fear in the lowest-threat episodes were not always the same as those toddlers
showing high levels of fear in the high-threat episodes—these latter types of children would likely be
categorized as behaviorally inhibited. Overall, less than one-third of the children showed consistently
high fear behavior across episodes, thus highlighting the problem with creating averages across episodes.
We also compared the two fearful temperament constructs: dysregulated fear and behavioral inhibition
(measured as the average of avoidant, wary, and fearful behavior across tasks). Although highly cor-
related (r = 0.60), this correlation was carried mainly by the children low in both behavioral inhibition
and dysregulated fear. Dysregulated fear predicted unique variance in social wariness at age 3, age 4,
and during the fall of kindergarten [9]. In addition, there is evidence that this pattern of displaying
higher levels of fear in putatively lower-threat situations is stable across a 3-year period [73]. In sum,
using a dysregulated fear approach provides a unique way to identify extremely fearful children by
focusing on high fear in lower-threat situations.
Similar to the behavioral inhibition literature, dysregulated fear has been associated with subsequent
development of social anxiety. In a recent study, children who showed a pattern of fear consistent with
a dysregulated fear profile were nearly four times as likely to show symptoms of social anxiety disorder
compared to children characterized as fearful or shy at age 5 (but not dysregulated at age 2) [73].
Further, dysregulated fear is associated with higher maternal-reported anxiety and/or social with-
drawal concurrently, at ages 3 and 4, and with teachers reporting anxiety in the child at the transition
to kindergarten [9]. This effect of dysregulated fear on social withdrawal and anxious behavior was
still significant after controlling for behavioral inhibition, highlighting the specific trajectory associ-
ated with a dysregulated fear pattern. In a follow-up study with observations through the summer after
the kindergarten year, children with a history of dysregulated fear were more likely to be reticent with
unfamiliar peers at age 5 [73].
In summary, decades of research have established that fearful temperament is a robust individual
difference characterized by wariness, fear, and avoidance of novel situations. These behaviors can be
reliably measured early in development (14 months) and predicted from distress and activity at 4
months of age. Although this literature has been dominated by behavioral inhibition, the new construct
of dysregulated fear is distinguishable from behavioral inhibition and has been shown to improve on
the prediction of social wariness across early childhood by identifying a more homogeneous subtype
of fearful children [9].
How Does Fearful Temperament Become a Disorder?
Not all inhibited/fearful children develop anxiety, either at subclinical or clinical levels, and some
even appear to grow out of this inhibited behavior. Perez-Edgar and Fox [29] suggest that a one-to-one
correspondence between early temperamental variation and anxious behaviors that appear later in
development will not be found because development does not occur as a simple unfolding of a single
trait or even set of traits. Development occurs via transactional processes involving interactions
between the child and his/her environment. In addition, biological processes also contribute to devel-
opmental trajectories in ways we are only beginning to understand [74, 75]. In this section, we will
address the following question: What factors account for the stability of inhibition/fear and also for
the trajectories toward maladjustment? That is, which of these children should we be worried about
and what are the processes linking this early-emerging behavioral style to development of maladaptive
outcomes. Biological, cognitive (attentional), genetic, and environmental (specifically, parenting)
influences will be discussed.
Biological Correlates and Mechanisms
In the previous sections, we have focused on the behavioral aspects of fearful temperament and devel-
opment of risk for anxiety disorders. Recently, there have been calls to integrate empirical findings
on the development of internalizing disorders (e.g., anxiety) across biological and psychological
(i.e., behavioral) domains [76]. Physiological measures implicate multiple systems (e.g., amygdala,
prefrontal cortex, autonomic nervous system, and neuroendocrine) in the neural circuitry of fear [58].
Dysregulation of physiological systems is common among children with internalizing disorders [77],
and numerous studies have documented physiological patterns associated with fearful behavior [60].
Many temperament researchers argue that the early emergence of individual differences in this and
other domains suggests a biological basis [10, 16, 78]. Specifically, Kagan has suggested that a proximal
cause of behavioral inhibition is a biological diathesis that gives rise to a pattern of fearful and anx-
ious behavior [15, 79]. However, we still lack a complete understanding of the biological–behavioral
link. This section provides a brief overview of this work; for more information on this topic, the
reader is referred to reviews elsewhere [17, 60].
Cortisol
A primary area of study has been the neuroendocrine responses of the hypothalamic–pituitary–
adrenocortical (HPA) system to stress and novelty, as indexed by cortisol production [79]. Atypical
cortisol patterns (e.g., high basal, altered diurnal, high reactivity) have been associated with fear,
extreme shyness, and social withdrawal in children [59, 80–84]. In a recent study, in contrast to a
pattern of lower levels of cortisol across the school year for the majority of children, Tarullo and
colleagues reported increasing cortisol levels across the school year for inhibited preschoolers [85].
This finding was most evident for inhibited children who were more popular and dominant with peers
compared to other inhibited preschoolers. However, other work only reports higher cortisol reactivity
for fearful, withdrawn behavior when other risk factors (e.g., insecure attachment, early maternal
stress) are present [72, 86], suggesting the complexity of the link between behavior and the HPA
system [87].
Autonomic Reactivity
Autonomic reactivity, including both the sympathetic (SNS) and parasympathetic (PNS) branches,
has been a central focus of research on stress sensitivity and the development of anxious/internalizing
problems [88, 89]. Physiological response patterns, such as increased heart rate or low heart rate
variability, of extremely inhibited children are believed to reflect an overall increase in SNS activity
[15, 39, 48, 90, 91]. However, changes in heart rate are influenced by both the SNS and PNS, so measures
specifically linked to these two branches have been the focus of the most recent research. The SNS
modulates PEP [92], which is the period between ventricular contraction and the semilunar valves
opening to eject blood into the aorta, such that increased sympathetic influence on the heart results in
a faster PEP due to increased contractility. PEP can be reliably measured in children making it a useful
noninvasive measure of SNS activity [93–95]. There have been only a few studies of temperament
and PEP associations in children. In a study of 24-month-olds, faster resting PEP was related to task-
specific freezing behavior, a measure of dysregulated fear [59]. For children high in temperamental
surgency (i.e., the opposite of fearful or inhibited), a lack of PEP reactivity to a stranger interaction
was associated with poorer emotion regulation [96], suggesting that for non-fearful children, SNS
reactivity has a positive influence on behavior. However, others have failed to find an association
between fear and PEP [97], suggesting that the type of fear or eliciting context may be important for
a full understanding of behavioral–biological associations.
Turning to PNS activity, decreases in respiratory sinus arrhythmia (RSA) (i.e., RSA suppression,
vagal withdrawal) are thought to represent the physiological underpinnings of emotion regulation
[89, 98, 99]. This interpretation relies on the assumption that decreases in RSA, across all contexts,
are indicative of good social–emotional outcomes [89]. Consistent with this interpretation, we have
found evidence that the dysregulated fear profile is associated with a pattern of RSA across tasks that
may reflect an additional risk factor [100]. In the toddler study described earlier, RSA was collected
at baseline and during each of the novel tasks, allowing for measures of RSA suppression across con-
ditions. Failure to suppress RSA across tasks was associated with the dysregulated fear profile and
more maternal-reported child anxiety symptoms [100].
Neural Correlates
As stated at the outset of this section, behavioral inhibition (and fear more broadly) is hypothesized to
develop from underlying biological vulnerabilities. In particular, it has been suggested that greater
stress and peripheral physiological reactivity (e.g., SNS reactivity) results from reactivity of the
amygdala and related circuitry including the frontal cortex [15, 101]. From the earliest studies of
frontal EEG asymmetry (where relative contribution of right and left hemisphere activation is inferred
from a difference score), fearful and inhibited behaviors have been associated with greater relative
right frontal activity [102, 103]. This pattern of activity has been found using baseline activity in
infants and children [41, 43, 51, 104, 105] and during tasks designed to elicit fearful behaviors and
withdrawal [84, 106, 107]. An association between relative right frontal activity and maternal-reported
fear for an unselected sample of infants has also been observed in a second-by-second analysis of
EEG asymmetry [108]. From recent research using source modeling analyses, evidence is emerging
that this relative difference in neural activity has been located in the right dorsolateral cortex in
humans [109] and nonhuman primates [70]. Finally, stability in frontal EEG asymmetry from 3 to 10
years of age accounted for stability in inhibited behavioral profiles for the most extreme group of
children [53]; and in another sample, 9-month right frontal asymmetry was associated with stability
in behavioral inhibition from infancy to age 4 [50]. Collectively, these data suggest that this pattern of
EEG asymmetry is a valid and sensitive neural marker for fearful temperament that can be used to
better characterize developmental trajectories and risk for anxiety disorders.
Neuroimaging studies provide further evidence of the neural circuitry of inhibited behavior.
The amygdala was first hypothesized by Kagan to be central to the development of inhibited behavior
[39]. Consistent with this, Schwartz and colleagues reported the first fMRI evidence of differences
in amygdala activity during novel stimuli presentation between adults with a history of behavioral
inhibition as toddlers and to those who were identified as uninhibited [110]. This finding has been
replicated and extended in a handful of informative studies that highlight the neural circuitry which
includes but is not limited to the amygdala and expand the contexts under which these associations
are observed [111–114]. For example, adolescents characterized as behaviorally inhibited as young
children show exaggerated amygdala activity while viewing emotion faces when asked to subjec-
tively report their fear level (vs. passive viewing) compared to uninhibited adolescents [111]. In other
words, passive viewing alone does not reveal a difference between inhibited and uninhibited adolescents,
and only during the putatively more stressful context of reporting on their own fear do the inhibited
and uninhibited adolescents differ in amygdala activity.
A series of three studies examining the circuitry of reward and punishment in inhibited adolescents
implicate the striatum and ventromedial prefrontal cortex but also highlight the importance of
eliciting context. Using the same sample as Perez-Edgar but a different task that contained cues for
potential reward and loss, Guyer and colleagues demonstrated differences between inhibited and
uninhibited adolescents in the striatal regions of the brain with greater activation for inhibited relative
to uninhibited adolescents even though there were no differences in performance [112]. The authors
interpret these findings as increased sensitivity to incentives (both rewarding and punishing) for inhib-
ited adolescents reflecting a potential vulnerability for developing anxiety disorders. In a separate
replication sample using a similar incentive task, when adolescents were lead to believe that their
performance was directly tied (contingent) to the incentives (reward or punishment) versus noncon-
tingent trials, behaviorally inhibited adolescents had greater striatal activity than uninhibited adoles-
cents [113]. Finally, when reward feedback was introduced into the design, greater differentiation
between the inhibited and uninhibited adolescents was observed, suggesting that inhibited adolescents
were more sensitive to feedback indicating no reward (i.e., negative feedback condition) [114].
In summary, biological dysregulation occurring across multiple systems characterizes children
who are temperamentally fearful. Although the bulk of this work has been with behaviorally inhibited
children (especially at the neural level), there is emerging evidence for altered physiology in children
with dysregulated fear as well. Collectively this work is consistent with the hypothesis put forth by
Kagan that this pattern of fearful and anxious behavior is the result of a biological diathesis [15, 79]
and with biologically based models of anxiety disorders [77].
Attentional Bias to Threat
The control of attention has long been hypothesized to be important in the maintenance of inhibited behav-
ior across development [115]. Evidence suggests that fearful children who are at risk for anxiety have
heightened vigilance to, and increased monitoring of, their surroundings compared to those not at risk [115,
116]. For instance, anxious individuals show an attentional bias toward threat-relevant stimuli (e.g., angry
faces) that non-anxious individuals do not exhibit [117]. See chapter “Neurobiology of Pediatric Anxiety
Disorders” for a more thorough review of attentional bias to threat and pediatric anxiety disorders.
Control of attention away from putatively threatening novel stimuli in infants is associated with
reductions in distress [118, 119], while sustained attention toward novelty has been associated with
fearful behavior, anxiety [120, 121], and greater social wariness/anxiety in kindergarten [120]. Fox
and colleagues have contributed to this literature by demonstrating that this type of attention bias, and
the control of attention more broadly, interacts with fearful temperament to predict anxiety develop-
ment in adolescents [122–125]. In a longitudinal study, from toddlerhood to adolescence, Perez-Edgar
and colleagues [123] demonstrated that a pattern of vigilance (i.e., low sustained attention to fixation
and high attention to distractor) in 9-month-olds was associated with greater behavioral inhibition as
toddlers and during middle childhood. In addition, the association between behavioral inhibition and
adolescent social discomfort (nervous behavior with peers) was significant only for the vigilant infant
group. Recent findings have extended this literature to a large sample of low-risk adolescents demon-
strating that attentional control moderated the relation between self-reported behavioral inhibition and
internalizing symptoms [126].
This is an exciting new area of research because of obvious connections to neurophysiology and
circuitry reviewed above. By examining neural processes underlying attentional biases, earlier
identification of risk may be revealed [127–129].
Genetics
Like many dimensions of temperament, fearful temperament and related anxious behavior have been
shown to be moderately heritable [130, 131]. Several twin studies have found significant heritability
for observed behavioral inhibition and inhibited behavior and parent-reported inhibited temperament
[132–136]. For example, Matheny [134] found evidence for genetic influences on the stability of
behavioral inhibition over time. However, other work suggests that genetic influences (i.e., heritability)
on behavioral inhibition decrease across the preschool years [137], indicating that environmental
influences may begin to shape this temperamental vulnerability. Other studies have found low herita-
bility estimates [138, 139]. Adoption studies have similarly yielded mixed results, with some finding
significant genetic influences [140], and others [141] finding low estimates of genetic influence on
parent-reported infant shyness. How genetic and environmental factors impact the trajectory from
fearful temperament to anxiety is still an open question [142]. In an adoption study, child social
inhibition was not directly associated with birth or adoptive parent anxiety [142]. However, for
children whose birth mothers met criteria for social phobia, social inhibition was associated with
attentional control when adoptive parents were also anxious. These results are consistent with differ-
ential susceptibility and biological sensitivity to context models [143, 144] which suggest that genetic
vulnerability is not deterministic but imparts a sensitivity to environmental influence.
Given that, overall, there seem to be at least moderate genetic influences on behavioral inhibition,
it is not surprising that children are more likely to be behaviorally inhibited when their parents have
an anxiety disorder. Behavioral inhibition has been found to be more common among parents with
panic disorder [145–148] and trait anxiety [149], although these associations are not always found
[150]. Although there is evidence for a direct relation between parental anxiety and children’s prone-
ness to anxiety, it is also likely that this link is facilitated by anxious parents’ actions with their fearful/
inhibited children. These include behaviors listed below, although it should be noted that these behav-
iors may be displayed by non-anxious parents as well.
Parenting
Several types of parenting are relevant to the relation between fearful temperament and later anxiety
outcomes. The following section discusses sensitive versus insensitive parenting in general, as well as
intrusive and protective parenting, specifically. The attachment relationship may also be considered a
context that influences anxiety development. Finally, influences on parenting behavior with tempera-
mentally fearful children are discussed.
Sensitive Parenting
Sensitive versus insensitive parenting is an important determinant of the outcomes of behaviorally inhib-
ited children. Defined by behaviors such as physical comfort, responsiveness to children’s cues, and
consideration of the child’s pacing during activities, the connotation of “sensitivity” is positive: sensitive
behaviors lead to adaptive outcomes for children. When examining outcomes of children broadly, this
notion is supported [151–153]. In the case of behaviorally inhibited children and anxiety-spectrum out-
comes, sensitive parenting has been found to alter the trajectory of inhibited behavior, such that toddlers
who were inhibited or shy and had mothers who were sensitive were less inhibited as school-aged chil-
dren than those whose mothers displayed lower sensitivity [154, 155]. Infants, especially boys, with
“difficult temperament” (similar to inhibited temperament in that it includes negative mood and high
withdrawal) were less likely to develop anxiety/depression symptoms as preschoolers if their mothers
displayed sensitive behavior than those whose mothers displayed lower sensitivity [156].
There are several mechanisms by which maternal sensitivity may protect behaviorally inhibited
children from developing increased anxiety. Maternal sensitivity may facilitate toddlers’ development
of effective regulation of fear (e.g., by regulating attention, using behavioral distraction, or getting
appropriate support from a caregiver). For example, Glöggler and Pauli-Pott [157] found that children
whose mothers displayed higher sensitivity used more active regulation during a fear-eliciting situa-
tion than children of less sensitive mothers. Sensitive parenting may also protect inhibited toddlers
from developing poor peer relations, which has been found to be a common outcome for inhibited
children and a precursor to anxiety problems. Toddlers displaying anxious solitude, a similar construct
to behavioral inhibition, were found to contribute more positive and fewer negative interactions with
peers and to be more accepted and less rejected by their peers as older children when their mothers
had displayed sensitive parenting [158].
In contrast to these findings, other studies have found that maternal sensitivity maintains or exac-
erbates behavioral inhibition or increases the association between inhibition and later anxiety problems.
For example, Arcus [159] found that infants showing early signs of inhibited behavior were more
likely to be inhibited as toddlers if mothers were consistently responsive to their distress, which by
some definitions would be considered “sensitive,” and less likely to be inhibited if their mothers set
firm limits, which may be seen as less sensitive. Similarly, Mount et al. [160] found that very high
levels of maternal sensitivity related to more anxiety for inhibited toddlers. Park et al. [44] found that
infants high in negative emotionality showed increased inhibition as preschoolers if parents showed high
sensitivity and low intrusiveness. In these cases, “sensitivity” may have indicated a “coddling” parenting
style that prevented inhibited toddlers from developing more independent regulation skills [159].
The positive relation between highly sensitive parenting behavior and inhibition may be specific to
children already displaying highly inhibited behavior, as indicated by moderations by child tempera-
ment in the above studies. Specifically, Mount et al. [160] found that the relation between highly
sensitive parenting and toddler anxiety mentioned above did not hold for children who were less
inhibited; rather, maternal sensitivity related to lower anxiety for toddlers displaying low levels of
inhibition. Park and colleagues [44] found that the association between high sensitivity/low intrusive-
ness and inhibition was especially salient for more highly negative infants. Inhibited children may
require stronger (although still gentle) encouragement to interact with novelty and practice independent
coping skills than less inhibited children to avoid later anxiety problems.
These disparate findings cause some confusion about the precise nature of the relation between
parental sensitivity and inhibited temperament. Although the terminology may be inconsistently used,
we believe the results of these various studies can be summarized as a curvilinear relation between
parental “encouragement to approach/engage with novelty” and children’s inhibition and anxiety
(Fig. 2). At the extreme end of encouragement to approach/engage is parental behavior that pushes the
child towards novelty with so much force that it overwhelms his/her capacity for independent coping.
Most would agree that this constitutes “insensitive” behavior (and others have labeled this more
specifically as “intrusiveness,” described subsequently). At the opposite extreme resides parenting
behavior that actively prevents the child from approaching and engaging with novelty, keeping him/her
Protection Intrusiveness
Fig. 2 A conceptual graph of

the putative curvilinear
Inhibition/Anxiety
relation between
encouragement to interact
with novelty and inhibition/
anxiety over time. Extreme
ends of encouragement to
interact represent protection,
at the low end, and
intrusiveness, at the high end,
both of which may maintain
inhibition and lead to anxiety
over the course of
development Encouragement to Interact with Novelty
from practicing and mastering independent coping and regulation in novel and uncertain contexts.
Because this type of parenting behavior might also involve displays of warmth and affection, this
behavior might have been labeled as “sensitive” in studies finding a positive relation between sensi-
tive parenting and young children’s inhibited temperament and anxiety (some would label this “pro-
tection” or “overprotection,” also discussed below). Both of these extremes seem to relate to maintained
or increased inhibition and risk for anxiety problems over time. In the middle of this curve resides
what we would call “gentle encouragement.” This includes parental behaviors that provide the extra
encouragement that inhibited children require to come into contact and cope with novelty but do so in
a way that challenges children within their range of coping. These behaviors have been less frequently
studied, but we suggest that examples may include modeling interaction with novelty, verbally encour-
aging approach, and physically coaxing children to approach and engage at a slow pace. Gentle
encouragement may include behaviors labeled as “sensitive” in the above studies that find a negative
relation between sensitive parenting and children’s inhibited temperament or anxiety.
There is some existing evidence for this curvilinear association. Mount et al. [160] found a
curvilinear relation between maternal sensitivity and toddler anxiety that existed for more inhibited,
but not less inhibited, toddlers. When mothers were very low or very high in sensitivity, inhibited
toddlers displayed more anxiety. At moderate levels of sensitivity, inhibited toddlers displayed less anxi-
ety. We suggest that to more clearly understand the relation between parenting and behavioral inhibition
and subsequent anxiety, “sensitivity” may be too vague of a term and more specific descriptions of
behaviors should be used. To this end, we are currently in the process of examining such a curvilinear
relation with parenting behavior that explicitly positions intrusive, gently encouraging (i.e., modeling
and slow-paced approach), and protective behavior along a continuum of an “encouragement to approach/
engage” variable. A body of research supports the positioning of intrusiveness and protection at the
two ends of this continuum and their positive relation to behavioral inhibition and anxiety.
Intrusive Parenting
Intrusive behavior occurs when parents push children to interact with novelty too fast or with too
much force or they intrude on and take over children’s independent activity. Intrusiveness has been
found to moderate the stability of inhibition, such that inhibited toddlers are more likely to continue
to show inhibited behavior later in childhood when their parents engage in more intrusive behavior
with them [23]. Therefore, intrusiveness is located on the far right side of “encouragement to approach/
engage with novelty” in Fig. 2. This may occur because intrusive parenting takes control of the situa-
tion away from the child, fostering helplessness and preventing them from being able to build adap-
tive coping skills during times of uncertainty [161]. Indeed, intrusive parenting behavior has been
related to increased stress reactivity for inhibited toddlers [72].
Sometimes related to intrusive behavior are other negative parenting behaviors like derision, criti-
cism, and emotional over-involvement, the latter two comprising the construct of “expressed emo-
tion.” Bivariate relations have been found between these constructs and inhibited temperament,
although results are somewhat inconsistent across studies [162, 163]. Moreover, negative parenting
behaviors have been found to predict and maintain inhibited temperament over time. For example,
Rubin et al. [23] found that inhibition shown with peers during toddlerhood predicted continued inhi-
bition (in the form of social reticence) at age 4 only when mothers were highly derisive.
Protective Parenting
Protection and overprotection, along with Rubin’s construct of oversolicitousness (all of which we
will refer to under the umbrella term of “protection” or “protective behavior” from here forth), have
been conceptualized as restrictions on children’s exploration and new experiences as well as exces-
sive physical comfort when these responses are not warranted [23, 120, 160, 161, 164–167], and
would thus reside on the far left side of the continuum of “encouragement to approach/engage with
novelty” depicted in Fig. 2. Protective behavior has been linked to inhibited temperament [167, 168]
and has been found to moderate (i.e., increase) the stability from temperamental inhibition and
related constructs (e.g., reticence with peers) to later indices of inhibition (e.g., social wariness, social
withdrawal) and anxiety [23, 49]. Edwards et al. [168] found that both preschool temperamental inhi-
bition (measured as parent-reported behavioral wariness with adults and peers and in unfamiliar
and challenging situations) and protective parenting predicted children’s anxiety symptoms (diagnos-
tic criteria for anxiety disorders) 1 year later, above and beyond stability in anxiety. Protective behav-
ior may maintain inhibited and anxious responses to novelty and uncertainty over time by assuming
regulation of the child and situation so that the child does not practice and learn independent coping and
regulation. Even within the situation, protective behavior may prevent the alleviation of distress [169].
Attachment
Unlike the above constructs, which are concerned with behavior as a parent characteristic, the quality
of the attachment relationship between parent and child is a relational construct that has also been
found to influence trajectories of inhibited children. A secure attachment relationship is conceptual-
ized as reflecting the child’s experience of a history of warm, responsive parenting [170]. An insecure
relationship, particularly the insecure-resistant subtype, which is conceptualized as a history of incon-
sistent or inadequate responses from the caregiver, seems to be a risk for anxiety problems. According to
attachment theory, children who receive inconsistent responses from caregivers maintain anxiety about
the availability of their caregivers that is not relieved when they return from a separation [170–172].
Infants in insecure–resistant relationships therefore develop strategies of arousal and vigilance that
carry over to other relationships and situations. This is supported by research showing that insecure
attachment is related to behavioral inhibition [173] and that behaviorally inhibited children who have
an insecure attachment relationship show higher salivary cortisol levels than those who have a secure
attachment [72, 174]. Although there has been some debate about whether temperament and attach-
ment represent unique constructs [175], it has generally been found that they make both independent
and interactive, rather than redundant, contributions to anxiety outcomes, such that inhibited children
who also have insecure–resistant attachment relationships with their primary caregiver are at the
highest risk of developing anxiety problems [149, 176–178]. Insecure attachment has also been found
to increase the stability of inhibited behavior across the first two years of life [43].
Influences on Parenting Behaviors
Thus far, parenting behavior has been discussed as a determinant of outcomes for inhibited children.
Of course, the association between parenting behavior and inhibition is likely bidirectional. A central
tenet of the developmental psychopathology perspective is that children play an active role in influencing
their environments [19], and evidence is mounting for such a conceptualization in relation to inhibited
temperament. Thus, toddlers’ temperament and behaviors are important influences on parents’ behav-
iors. Much of the work in this area has focused on the influence of toddler inhibition on protective
parenting. For example, parents’ perceptions of their children’s inhibition (fearfulness, shyness) have
been found to predict future protective parenting [179, 180].
Inhibited children may be particularly likely to elicit protective responses when they face feared,
novel, and uncertain situations. Thus, some recent work has focused on protective behavior enacted
by mothers in response to such solicitations during laboratory novelty tasks. Consistent with the con-
ceptualization that inhibited children elicit protective behavior, which then increases the likelihood of
further inhibition and anxiety, results suggest that solicited maternal protection mediates the relation
between toddler inhibition and anxious behavior observed in preschool-aged children [164] and
kindergarteners [120]. Furthermore, the context of this solicited maternal protective behavior appears
to play an important role in whether it facilitates the relation between toddlers’ inhibited temperament
and later anxious behavior. Similarly to how inhibited behaviors in low-threat contexts seem to identify
toddlers at risk for later anxiety problems [9], protective behavior displayed in low-threat, but not
in high-threat, contexts relates to inhibited temperament and mediates the relation between age 2
inhibited temperament and age 3 shyness [181]. These results are consistent with the theoretical
notion that the development of independent regulation and coping occurs in situations that are chal-
lenging yet not overwhelming and that parental intervention during these situations may disrupt this
important learning process [182].
Parents’ own characteristics, including anxiety and depression symptoms, cognitions, and emotion
processes, also influence whether they engage in particular behaviors. As mentioned previously,
parental anxiety relates to children’s inhibited temperament, and one mechanism besides shared
genetic liability may be the higher likelihood of engaging in anxiogenic parenting. For example, anxious
mothers have been found to grant less autonomy and be more critical, and these behaviors subse-
quently predict child anxiety [183]. Maternal depression has similarly been investigated as an influence on
parenting behavior. Some of the aforementioned parenting behaviors, including criticism, protective
behavior, and related or other problematic behaviors such as not granting autonomy and disengage-
ment, have been found to be related to maternal anxiety and depression [183–186]. Further, these
behaviors have been associated with children’s inhibited temperament and anxiety specifically for
mothers with anxiety disorders or high levels of trait anxiety, but not (or less so) for mothers with low
levels of anxiety [187, 188].
Parents may behave differently with their inhibited children depending on how they understand,
think about, and anticipate fearfulness and shyness. Rubin and colleagues have identified parenting
beliefs as characteristics that shape subsequent behavior. Mills and Rubin [189] defined parenting
beliefs as cognitive/affective processes that direct the strategies parents use to socialize social compe-
tence in their children. In the case of inhibited temperament, these processes may consist of attitudes
about inhibition, goals for the situation in which inhibition is shown, attributions about causes
(i.e., internal or external, stable or unstable) for inhibited behavior, and emotional responses to displays
of inhibition. In general, parents tended to respond to inhibited behavior with the emotions of confusion
and concern and to attribute inhibition to transient states rather than stable characteristics [189].
Of course, individual differences exist in these beliefs. Beliefs may be different for parents of more
temperamentally inhibited children than parents of other children. Compared to mothers of less inhib-
ited boys, mothers of temperamentally inhibited boys have reported being less confused about inhibited
behavior and more focused on relational goals (wanting to maintain a positive relationship and help
their children develop social skills) [179]. Other studies have found that mothers of temperamentally
inhibited or anxiety-prone children were more likely to endorse parent-centered goals (i.e., wanting a
“quick fix” for the situations without regards for the child’s perspective) than mothers of children who
did not exhibit temperamental vulnerability towards anxiety [190]. Beliefs appear to be associated
with both parents’ subjective perceptions of inhibition and objective measures of children’s physio-
logical dysregulation [166, 191]. For example, baseline cardiac vagal tone in 2-year-old children
predicted beliefs in restrictive parenting 2 years later [191]. Parenting style has also been found to be
related to beliefs, such that more authoritarian mothers endorse fewer relational goals, attribute inhi-
bition to dispositional characteristics, and report more embarrassment in response to shyness [192].
Certainly, the relation between parenting style and beliefs may be bidirectional in nature. Finally,
beliefs may be shaped by the perspective of one’s culture on inhibition. For example, mothers in
Eastern cultures have been found to be more accepting of inhibited behavior, whereas mothers in the
Western cultures are less accepting and more negative about inhibition [193, 194]. These beliefs then
translate into parenting behavior. Mothers who view their inhibited children as dispositionally inhibited
(attributing inhibition to internal and stable causes rather than situational and unstable causes), and
therefore vulnerable, are less likely to encourage independence and more likely to behave punitively,
protectively, or in a controlling manner, at least in North American samples [180, 193].
Recent work has focused on a different type of cognition: the accuracy with which parents anticipate
their child’s inhibited behavior. In an initial study on maternal accuracy, this construct was operational-
ized as the statistical relation between mothers’ predictions about toddlers’ reactions to emotion-eliciting
stimuli and toddlers’ actual reactions [195]. Across several studies, mothers of inhibited toddlers tended
to be more accurate in predicting inhibition or fearful distress than mothers of less inhibited toddlers
[120, 164, 181]. Maternal accuracy appears to be more than a reflection of toddler inhibition, however.
In these studies, maternal accuracy served a moderating role in the relation between inhibited tempera-
ment and protective parenting. The more accurately mothers anticipated their children’s distress to novel
situations, the higher the relation between inhibited temperament and protective behavior. So, when
toddlers display inhibited temperament and mothers are particularly attuned to impending displays of
this behavior, they may be more likely to enact protection. The context of situations in which this rela-
tion unfolds appears to be important [181]. Specifically, in situations that are highly stressful for children
(i.e., when stimuli more universally elicit fearful responses and are physically intrusive), inhibition and
accuracy do not relate to protection. In these situations, protective behavior may be a more universal
response by parents and not tied to anxiety processes. In situations that, although novel, are presented in
a friendlier manner and allow the toddler more time and space to cope, inhibited temperament and accu-
racy interact in relation to protective behavior. In this case, protection is less warranted and may depend
more on maternal cognitions about the situation than when the characteristics of the situation itself
(the universally threatening nature of it) dictate a response.
Conclusion
In this chapter, we have provided a broad overview of the literature on fearful temperament highlighting
its identification in children, risk for social and anxiety problems across development, and biological
and parenting factors associated with individual differences and risk trajectories. Taken together, the
literature reviewed provides compelling evidence that this early-emerging individual temperament is
a key risk factor for the development of anxiety disorders later in childhood.
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Part II
Anxiety Disorders
Generalized Anxiety Disorder in Children
and Adolescents
Golda S. Ginsburg and Nicholas W. Affrunti
Abstract This chapter presents an overview of pediatric generalized anxiety disorder (GAD). Youth
with GAD worry excessively, are unable to control their worry, and experience significant distress and
impairment as a result. Previously referred to as overanxious disorder, GAD is common and highly
comorbid with other anxiety disorders. The etiology of GAD is multi-determined encompassing bio-
logical and environmental influences. If left untreated, the disorder can be chronic and predictive of
adulthood anxiety and depression. GAD-specific assessment tools are now available, including those
that target unique cognitive aspects of the disorder. Evidence-based treatments for pediatric GAD
involve cognitive and behavioral (CBT) and pharmacological interventions. Recent psychosocial
interventions have tailored CBT to specifically target worry.
Keywords Worry • Generalized anxiety • Overanxious • Pediatric • Children • Adolescents
Case Scenario
Daniel is a 13-year-old Caucasian male who presented at our clinic with complaints of insomnia and
feeling like he could “not turn off his brain.” He reported thinking about things over and over again
and was unable to control his thoughts when it was time to go to sleep. When asked about the content
and nature of these thoughts, he reported thinking about getting bad grades in school, a poor play he
made in a baseball game, if his parents had enough money, if he is going to get into a good college,
and natural disasters. He stated that these thoughts would bother him both at night and during the
day. When these thoughts occurred during the day, he reported feeling “stressed out” and would often
lash out at others, even if they did not deserve it and acknowledged getting into frequent arguments at
home with his parents and siblings. While Daniel stated that he typically had good friendships and
was involved in sports and other activities, he was beginning to dislike school because it was causing
him too much stress and his grades had been getting worse over the past year. He also reported get-
ting headaches and stomachaches that had no medical etiology according to his pediatrician.
G.S. Ginsburg (*)

Division of Child and Adolescent Psychiatry, The Johns Hopkins University School of Medicine,
Baltimore, MD, USA
e-mail: gginsbu@jhmi.edu
N.W. Affrunti
Department of Psychological and Brain Sciences, University of Louisville, Louisville, KY, USA
72 G.S. Ginsburg and N.W. Affrunti
Description of the Disorder
Daniel has generalized anxiety disorder (GAD). This disorder is characterized by persistent and
excessive worries about a number of different issues, coupled with one or more somatic symptoms
(refer to Table 1 for full diagnostic criteria). These symptoms cause significant distress and impair
daily functioning [1]. Children with GAD are often overly self-critical, evaluating themselves in an
all-or-nothing fashion [2]. Frequently, this leads youth to avoid activities where they feel they may not
be able to perform perfectly and to seek excessive reassurance from teachers, caregivers, and others
about their performance [3]. Children with GAD have relatively few friends when compared to their
nonanxious peers but appear comparable to nonanxious peers in the quality of their peer relationships,
frequency of contact with friends, and the ability to make new friends [4]. Relative to children with
other anxiety disorders, youth with GAD tend to have more somatic symptoms (e.g., headaches,
stomachaches, muscle tension, restlessness) and sleep disruptions [5, 6].
Children with this clinical profile were first diagnosed in DSM-III using overanxious disorder
(OAD) rather than GAD. However, because the OAD diagnosis had poor reliability and validity [7, 8]
and symptoms of OAD overlapped with GAD [9, 10], the diagnosis of OAD was eliminated in
DSM-IV and was incorporated into GAD (see Table 1). With the upcoming release of DSM-V, the
proposed diagnostic criteria have again been revised. Relevant to diagnosing children, the first change
reduces the length of time the worries have to be present from 6 months to 3 months. There is prelimi-
nary evidence that this criteria change may have the most pronounced effect on rates of GAD [11].
Another proposed change is the removal of criteria B, “The worry is difficult to control,” as this was
considered redundant with the “excessive” criterion (see Table 1).
The primary symptom of GAD, worry, is a relatively common phenomenon in typically developing
children and adolescents, with 80 % of youth (age 7 years and older) and almost 50 % of younger-
aged children (ages 4–6 years) reporting at least one worry [12]. The most common worries reported
by normal children were personal harm and/or harm to others, dying, and test performance, all reported
by over 13 % of the sample [12]. The most frequently reported worries among clinically referred
youth were related to health (self and others), school, personal harm, natural and human-made disas-
ters, and problems with peers [13]. Although children with GAD appear to worry about similar things
as their nonanxious peers, they do so in excess [14]. For example, children with GAD (and OAD)
endorsed an average of six worries, while those not diagnosed with GAD (or OAD) only endorsed an
average of one worry. Furthermore, children with GAD (or OAD) have a higher frequency of worries
that are recurrent, are more difficult to control, and result in greater interference in functioning [15].
This pattern is also true when comparing children with GAD to those diagnosed with another anxi-
ety disorder [10, 13, 14]. Pina et al. [16] found that children and adolescents who reported excessive
and uncontrollable worry about their own health, family, or school were 10–25 times more likely to
receive a GAD diagnosis (relative to another anxiety disorder) than those children who did not report
excessive and uncontrollable worry in one of those areas. There is a clear difference between the
amount, intensity, uncontrollability, and sometimes even content of the worry reported by children
with GAD compared to the worries of nonanxious children or those children with another anxiety
disorder.
The diagnosis of GAD is one with a considerable history of controversy, primarily due to the
finding of high rates of comorbidity between GAD and other anxiety and mood disorders [17].
Specifically, it has been argued that GAD, rather than a unique psychiatric disorder, is a prodromal
condition, a risk factor for other emotional disorders, or a subtype of major depression [18, 19].
However, data is accumulating to contradict this claim. For instance, in a recent study of 3,021 indi-
viduals followed for 10 years (age 14–24 years at baseline, 21–34 years at follow-up), GAD was
found to be more related to anxiety, than depressive disorders [20], suggesting there are different
developmental patterns for GAD and depressive disorders. In an analysis of 5,001 individuals from
the National Comorbidity Survey (NCS) and NCS follow-up survey, GAD and major depressive
Generalized Anxiety Disorder in Children and Adolescents 73
Table 1 Diagnostic criteria for pediatric generalized anxiety disorder

Generalized anxiety disorder (Proposed) Generalized anxiety
Overanxious disorder (DSM-III-R) (DSM-IV-TR) disorder (DSM-V)
A. Excessive or unrealistic A. Excessive anxiety and worry A. Excessive anxiety and worry about
worry for at least 6 occurring more days than two or more domains of activities
months of 4 or more of the not about a number of events or events (domains like family,
following: or activities for at least 6 health, finances, and school/work
1. Future events months. difficulties)
2. Past behavior B. The worry is difficult to B. The excessive anxiety and worry
3. Competence (school, control. occur on more days than not for
peers) C. Anxiety and worry are three months or more
4. Somatic complaints associated with at least C. The anxiety and worry are
5. Self-consciousness three (one for children) of associated with one or more of the
6. Need for reassurance the following: following symptoms:
7. Tension, inability to relax. 1. Restlessness or feeling 1. Restlessness or feeling keyed
Generalized Anxiety Disorder keyed up or on edge up or on edge
(DSM-III-R) 2. Being easily fatigued 2. Being easily fatigued
A. Excessive or unrealistic 3. Difficulty concentrating 3. Difficulty concentrating or mind
anxiety or worry about 2 or or mind going blank going blank
more life circumstances for 4. Irritability 4. Irritability
at least 6 months, where the 5. Muscle tension 5. Muscle tension
person is bothered by these 6. Sleep Disturbance 6. Sleep disturbance
concerns more days than not. D. The anxiety, worry, or D. The anxiety and worry are
B. At least 6 of the following physical symptoms cause associated with one or more of
are present while anxious: clinically significant the following behaviors:
Motor tension: distress or impairment in 1. Marked avoidance of
1. Trembling, twitching, social, occupational, or situations in which a negative
feeling shaky other important areas of outcome could occur
2. Muscle tension, aches, functioning. 2. Marked time and effort
soreness; preparing for situations in
3. Restlessness which a negative outcome
4. Easy fatigue. could occur
Autonomic hyperactivity: 3. Marked procrastination in
1. Shortness of breath/ behavior or decision-making
smothering sensation due to worries
2. Palpitations, tachycardia 4. Repeatedly seeking
3. Sweating or cold, clammy reassurance due to worries
hands;
4. Dry mouth
5. Dizziness or
lightheadedness
6. Nausea, diarrhea, other
abdominal distress
7. Flushes (hot flashes), chills
8. Frequent urination
9. Trouble swallowing/“lump
in throat.”
Vigilance and scanning:
1. Feeling keyed up, on edge
2. Exaggerated startle
response
3. Difficulty concentrating,
mind going blank because
of anxiety
4. Trouble falling or staying
asleep
5. Irritability
Bolded criteria show additions and changes to the diagnostic criteria of OAD/GAD from DSM-III-R to the proposed
DSM-V criteria
episode were found to have distinct determinants, and the stability of these disorders could not be
explained by a single underlying internalizing factor [21]. Moreover, data revealing that GAD can
either precede or follow other anxiety and mood disorders are inconsistent with classifying it as a
prodromal or residual condition [22, 23].
Prevalence
Community Samples
Early epidemiological studies, using OAD criteria, report prevalence rates from community samples
ranging from 7 % [24] to 12.4 % [25]. More recent studies, using the DSM-IV criteria for GAD,
report lower prevalence rates ranging from 0.1 % [26] to 3.3 % [27]. The lower rates of GAD shown
in community samples, compared to those of OAD, may be due to the addition of impairment criteria
for GAD in DSM-IV [28]. The wide range of prevalence rates is due to variability in sample charac-
teristics (e.g., age), diagnostic instruments, reporters, degree of severity and impairment required,
criteria used for diagnoses (e.g., OAD versus GAD), and setting.
Clinical Samples
Prevalence rates of OAD/GAD in clinical samples also vary widely and for similar reasons as the
range published in epidemiological studies. In general, in outpatient clinics, rates of GAD are reported
to range from 3 % [29] to as high as 15 % [30]. Prevalence rates of OAD in samples referred to spe-
cialized anxiety clinics range between 12 % [8] and 53 % [9]. Prevalence rates of GAD, using DSM-IV
criteria, in samples referred to specialized anxiety clinics range between 19 % [31] and 43 % [32].
GAD was the most common anxiety diagnosis in these samples and is generally the most prevalent
diagnosis seen at specialized anxiety clinics [33, 34].
Age
The prevalence of both OAD and GAD increases with age. In a community sample of preschoolers
(age 4 years), the prevalence rate of GAD, using DSM-IV criteria, was less than 1 % of the sample
[35]. Merikangas et al. [26] found a similar rate (0.1 %) in a community sample of children 8–11 years
of age. However, that rate grew to 1.1 % for adolescents (ages 12–15 years). Costello et al. [36]
reported that the 3-month prevalence rate of GAD dropped from ages 9–10 to 12–13 years, then rose
steadily thereafter. Studies using OAD criteria have found similar increases in adolescents. For
instance, Kashani and Orvaschel [25] reported a prevalence rate of 8.6 % in a community sample of
8-year-olds and 17.1 % among 17-year-olds.
Consistent with the prevalence of GAD, symptoms of GAD or worry also show an overall increase
with age [12, 37, 38]. One explanation for the increase in GAD and worries as children age is the
change in cognitive skills, which plays a key role in the etiology and maintenance of GAD. Specifically,
as children age, they become more aware of future possibilities, deduce the threats that could result,
and think of more negative consequences of these threats [39]. Rapee [40] posits that the increase in
the prevalence of GAD symptoms over time may also be due to increases in GAD symptoms in girls
rather than a general increase.
The content of worry also appears to vary with age. Younger children (under 6 years) are more
likely to worry about separation from their parents and burglars, while older children (10–12 years)
are more likely to worry about tests and academic performance, death, physical appearance, and
social ills [12]. Masi et al. [41] found that children (7–11 years) compared to adolescents (12–18
years) with GAD reported significantly more need for reassurance and significantly less brooding.
Pina et al. [16] investigated the symptoms present in 111 children (6–11 years) and adolescents
(12–17 years) diagnosed with GAD and found that adolescents endorsed more physical symptoms
than children.
Gender
Gender differences in the prevalence of OAD/GAD in children and adolescents are inconsistent.
Merikangas et al. [26] reported no gender differences in a sample of 8–15-year-olds, using the DSM-IV
criteria for GAD, drawn from a community sample. In other community samples, using the OAD
criteria, girls (of all ages) were found to have higher rates than boys (15 % of girls and 9 % of boys;
[25]). Clinical samples have reported no gender differences in OAD/GAD in children 9–13 years of
age [42, 43]. There remains a lack of conclusive research looking at gender differences in clinic
samples in older adolescents.
With respect to symptoms of GAD and/or worry, females report more GAD symptoms than males.
In a sample of 1,653 adolescents, 14–18 years, females reported more GAD symptoms than their male
counterparts [44]. In a sample of African-American adolescents (12–19 years), females self-reported
more GAD symptoms than males [45]. The reason that females report more GAD symptoms than
males may be due to their beliefs about worry. A study of 16- to 19-year-old students found that
females were significantly higher on their positive beliefs about worry [46]. That is, women may be
more likely to worry because they believe that worry is a useful cognitive strategy. More research is
necessary to identify and understand gender differences in GAD and worry.
Race/Ethnicity
Though data on the prevalence of OAD/GAD across racial and ethnic groups is sparse, the results are
generally consistent. Data from specialized anxiety clinics report similar rates of OAD/GAD in
Caucasian and minority children (e.g., [43, 47, 48]). Consistent with the prevalence rates of GAD
across racial/ethnic groups, no differences in the manifestation or severity of GAD symptoms have
been found across racial or ethnic groups [45, 49]. For instance, Austin and Chorpita [50] reported
that Caucasian, Chinese American, Filipino American, Native Hawaiian, and Japanese American
children, 7–18 years, all showed similar levels of GAD symptoms, as rated by child self-report.
Course
Early studies based on retrospective reports suggested that a significant proportion (44 %) of adults
with GAD recalled that the onset of their illness began in childhood [51]. Prospective studies of GAD,
though few in number, reveal that GAD is fairly stable over time, suggesting it is a chronic illness if
left untreated. This literature, however, is inconsistent due to variations across studies noted earlier
(e.g., in the diagnostic criteria used, informants, and samples). For instance, in a community sample
of over 300 children (9–18 years) evaluated over a 2.5-year period, half of the subjects that were
diagnosed with OAD/GAD at time 1 were again diagnosed with OAD/GAD at time 2; findings did
not vary by age or gender [52]. In contrast, Essau et al. [53] followed a community sample of German
adolescents with a broad range of anxiety disorders (AD) and found that 77 % of the adolescents with
a current AD at time 1 no longer met diagnostic criteria (using the World Health Organization
Composite International Diagnostic Interview; CIDI) at time 2 (average of 15 months later). Factors
associated with the stability of anxiety disorders, though not unique to GAD, included older age, more
negative life events, and the presence of comorbid somatoform or substance use disorders. In a clini-
cal sample, Carballo et al. [54] found that GAD was less stable relative to other anxiety disorders such
as specific and social phobias (SOPs). No significant sex differences were observed on the diagnostic
stability of the anxiety disorder categories studied.
In addition to being fairly stable, GAD and worry appear to be risk factors for later anxiety and
depressive disorders. For instance, in a community sample of 712 adolescents, OAD was strongly
associated with early-adulthood diagnoses of GAD, depression, and SOP [55]. Data from the Great
Smoky Mountains Study [56] revealed that childhood OAD was associated with later OAD, panic
attacks, depression, and conduct disorder (CD), while childhood GAD was related only to conduct
disorder. Beesdo and colleagues [20] followed a community sample (N = 3,021, 14–24 years at time 1)
for 10 years. GAD, phobias, panic disorder, and depressive disorders predicted each other over time,
and early-onset GAD was a stronger predictor of later anxiety rather than depressive disorders. Several
variables predicted GAD onset over time (and they were similar to those found for other anxiety disor-
ders) including parental GAD and depression, childhood behavioral inhibition, childhood separation
events, and parental overprotection. Uniquely, GAD was associated with the personality trait “reward
dependence” (based on self-reported personality) and dysfunctional family functioning. In sum, GAD
and associated worry appears stable and is associated with a broad range of downstream disorders.
Differential Diagnosis
Distinguishing GAD from other anxiety disorders can be difficult because many of the symptoms
overlap with other anxiety disorders and rates of comorbidity are high. For example, children with
OCD and GAD may present with complaints of excessive thoughts or worries that can be intrusive.
To differentiate between the two disorders, determining the nature of the thoughts or worries is criti-
cal. Youth with GAD generally worry about everyday or real-life problems (e.g., test performance,
school, friendships), while youth with OCD have thoughts that are typically not connected to every-
day events and have a more unrealistic quality (e.g., contamination by germs) [1]. For a child experi-
encing worry about social situations, differentiating between SOP and GAD is key. Youth with GAD
tend to worry more chronically and across several situations (social and nonsocial), whereas youth
with SOP generally experience social anxiety only and in the context of social evaluative cues. For
those already diagnosed with a different Axis I disorder (e.g., panic disorder), the excessive worry
must be unrelated to that disorder (e.g., cannot be worried about having a panic attack) for it to be
considered a symptom of GAD.
Etiology
Several etiological models of pediatric GAD have been proposed [40, 57]. The most recent, by
Kertz and Woodruff-Borden [57], is presented in Fig. 1. Briefly, according to these developmental
models, a child with GAD is born with a vulnerability to anxiety (manifested by heightened arousal
Parental Factors
Parent Parent Anxiety Parenting

Anxiety Modeling Behaviors
Parent-Child
Relationship
Biological Vulnerability Factors Cognitive Vulnerability Factors
Genetic Problem Intolerance of

Factors Orientation Uncertainty
Worry
Temperament
Beliefs Information
About Worry Processing
Responses to Affect
Emotion
Avoidance
Regulation
Development Over Time*
Fig. 1 Etiological model of pediatric generalized anxiety disorder (GAD). From Kertz et al. [57] used with
permission
and emotional reactivity). This vulnerability may be inherited from an anxious parent or other family
member. Children’s biological vulnerability, such as deficits in cognitive (e.g., information process-
ing) and affective (e.g., emotion regulation) functioning, increases their behavioral avoidance, ulti-
mately maintains and/or exacerbates worry and anxiety, and leads to considerable distress and
impairment. Parents of these youth, either due to their own anxiety or in response to their child’s
temperament, respond with greater overprotection and other anxiety-enhancing parenting behaviors
(e.g., criticism) that also perpetuate the child’s anxiety.
Despite the empirical advances that have informed these models, it should be noted that not all
components have empirical support, the magnitude of each component’s contribution is unclear, and
unknown etiological factors likely exist. Some aspects of this model have support in adults (e.g.,
cognitive factors) but not children, and most of the factors proposed in the etiology of GAD also play
a role in the development of other pediatric anxiety disorders. Data determining the specificity of
these etiological factors for GAD awaits future investigation. Despite these limitations, there is a
consensus that GAD is multi-determined with both biological and environmental factors playing key
roles that influence each other in a transactional manner over a child’s development. The evidence for
key components of etiological models is briefly discussed below.
Heritability
Research based on family aggregation and twin studies support claims that anxiety runs in families.
Studies that have focused on GAD, using adult twins, have found that genes accounted for approxi-
mately 30 % of the variance in GAD symptoms [58–60] and similar results have been found with
child samples [61]. However, it has been hypothesized that the genetic link is likely to be for anxiety
as a broad construct and/or emotional reactivity rather than for a specific disorder [59, 62]. More
recently, researchers have focused on identifying candidate genes, with preliminary data suggesting
that anxiety disorders are associated with serotonin genes (see [63] for a review), though again the
specificity of these findings for GAD are not clear.
A related area of research supporting the heritability of anxiety comes from studies examining the
genetic basis of temperamental and cognitive vulnerabilities that purportedly mediate the relationship
between genes and anxiety disorders. Behavioral inhibition (BI) is the temperamental style most
highly linked with anxiety and is characterized by increased physiological arousal and fear of novel
stimuli [64]. However, the presence of BI has been associated with a broad range of anxiety disorders,
especially social fears and SOP, and the majority of youth with BI do not go on to develop an anxiety
disorder [65–67]. Thus, the association of BI with GAD specifically is insufficient at this time.
Cognitive Factors
A large body of data confirms that youth with GAD display problematic cognitive processes. Relative
to their nonanxious peers, youth with GAD are more likely to overestimate the negative consequences
of their actions, expect negative consequences to occur with greater frequency, overestimate the likeli-
hood of threatening situations, interpret ambiguity as threatening, and have impaired problem-solving
skills [68–70]. Recently some adult-based cognitive models and concepts have been explored in youth
(see [57, 71] for reviews). These adult cognitive models include the avoidance model [72, 73], meta-
cognitive models (e.g., [74, 75]), the role of intolerance of uncertainty [76], and problem-solving or
problem-orientation deficits [77]. Literature testing these adult models in youth, however, has only
indicated partial support. For instance, metacognitive models [74, 75] suggest that positive beliefs
about the usefulness of worry (i.e., worry superstitiously allows control over events) and negative
beliefs about worry (i.e., worry is dangerous and uncontrollable) play a role in the development of
GAD. Recent research has found that youth do endorse positive and negative beliefs about worry and
there is some support among both clinical (i.e., youth meeting criteria for OAD/GAD) and nonclinical
youth indicating that positive beliefs about worry are associated with greater worry severity [46, 78,
79]. Yet, several studies have failed to find a unique relation between positive beliefs about worry and
OAD/GAD [15, 80, 81]. A similar pattern of inconsistencies has been reported between negative
beliefs about worry and OAD/GAD [15, 81]. Thus, the relevance of this and other “adult” cognitive
models awaits empirical examination and validation among youth.
More consistent data supports the role of disturbances in information processing that cause and/or
maintain GAD (and other anxiety disorders). This body of work contends that youth with GAD are
more likely to interpret ambiguous information as threatening and have an attentional bias toward
threatening stimuli. Data from studies using experimental threat tasks such as the dot probe and the
emotional Stroop tasks indicate that children with GAD, versus nonanxious peers, show a faster reac-
tion time to threatening, compared to nonthreatening stimuli [82–86]. For instance, Waters et al. [87]
examined the attentional bias for angry and happy faces in 7- to 12-year-old children with GAD
(N = 23) and nonanxious controls (N = 25) and found that GAD severity was associated with greater
attentional bias toward angry faces. It is hypothesized that vigilance for threat involves interactions
between the amygdala and the ventrolateral prefrontal cortex, which constitute a neural circuit that is
responsible for threat, and that disturbed interactions between these structures may result in hyper-
vigilance and anxiety [88] (see chapter “Neurobiology of Pediatric Anxiety Disorders” for a more
detailed discussion).
Parenting and the Parent–Child Relationship
Several reviews and meta-analyses have confirmed a relation between specific parenting behaviors
and anxiety symptoms/disorders in youth [89–93]. Though inconsistent findings across studies exist,
parental behaviors such as overcontrol (including overinvolvement and less autonomy granting),
modeling of anxiety, low acceptance and warmth, as well as high catastrophizing and criticism have
been linked to high levels of child anxiety overall. The amount of variance accounted for by these
parenting variables is small (collectively likely to be less than 20 %). The impact of parental behaviors
is also believed to be moderated by child gender, child age, socioeconomic status, and type of interac-
tion task used to measure parenting [94, 95]. Interventions targeting parents and parent behaviors have
shown evidence of reducing anxiety symptoms in their children [96]. Additional research is clearly
needed in this area. Few studies linking parenting behaviors and child anxiety are longitudinal; thus,
the direction of effects and long-term impact is uncertain. Evidence from longitudinal studies has
concluded that a reciprocal relationship exists: parental behaviors affect child anxiety and child anxi-
ety symptoms affect parental behaviors (e.g., [95, 97]).
Studies examining the relation between parenting and GAD or worry symptoms specifically are
sparse, though the pattern of findings parallels those in studies examining the link between parenting
and a broad range of anxiety symptoms/disorders. For instance, several studies using community
samples and child self-report measures report that perceived parental overprotection, anxious rearing,
overcontrol, warmth, and rejection are associated with higher levels of worry [98]. Findings, however,
varied by parent (mother, father) and child gender [99, 100]. Hale et al. [101], also using a community
sample, examined the relation between perceived parental alienation and GAD symptoms among
adolescents (ages 12–19 years; N = 1,106). Based only on adolescent reports of both constructs, the
authors found that higher perceived parental alienation, rejection, and control were associated with
higher GAD symptoms. Parental alienation and rejection made unique contributions to worry symp-
toms when all parenting variables were entered into a single model, and slight variations were noted
based on child age and gender.
In addition to specific parenting behaviors, parental attachment has been examined in relation to
worry and/or GAD. The construct of attachment, based on the work of Bowlby [102] refers to the
quality of the parent–child bond. Individuals with an insecure attachment (theorized to be the result of
early experiences with unpredictable caregiver responsiveness) are predicted to be at greater risk for
developing excessive anxiety and worry. With respect to worry, retrospective studies with adults [103,
104] have found that individuals with GAD are more likely to report an insecure attachment with their
mothers compared to their nonanxious peers (no comparisons between GAD and other anxiety disor-
ders were included). This relation is also present in child samples using cross-sectional designs. For
instance, Muris et al. [12] reported that an insecure attachment (avoidant or ambivalent), along with
perceived parental rejection and anxious rearing, was associated with higher levels of worry in a com-
munity sample of children (N = 159; ages 9–13). Brown and Whiteside [105] replicated and extended
this finding with a clinical sample of anxious youth (N = 64; 7–18 years). In this study, youth com-
pleted measures of parenting behaviors, a single-item measure of attachment style, and the Penn State
Worry Questionnaire (PSWQ). Parental attachment as well as parental rejection were positively
related to worry. Specifically, youth who classified themselves as ambivalently attached reported
higher levels of worry than did children who classified themselves as securely attached. Parental rejec-
tion and insecure attachment were both found to make unique contributions to worry [105].
Prospective studies, though few in number, also suggest that specific parenting behaviors and
attachment have long-term consequences with respect to child anxiety [106, 107]. For instance,
Ginsburg et al. [106] found that higher levels of parental criticism and lower levels of granting of
autonomy, assessed when children were in first grade, were associated with higher GAD symptoms in
sixth grade. Warren et al. [107] conducted a 16-year follow-up study of children (N = 172) classified
at 12 months of age on attachment style (i.e., secure, avoidant, ambivalent). At follow-up, among the
26 children (out of the total sample) that had at least one current or past anxiety disorder, a greater
number had an ambivalent compared to secure attachment. Furthermore, an ambivalent attachment
predicted childhood anxiety disorders even after accounting for maternal anxiety and temperamental
variables. Notably, the majority of youth classified as insecurely attached (i.e., 70 %) did not develop
an anxiety disorder and the relation of attachment to GAD specifically remains unclear.
Finally, a critical question remaining for future research is to identify the mechanisms by which
parental behavior or attachment style influences child anxiety and worry. In one of the few studies to
address this issue, Affrunti and Ginsburg [108] tested the hypothesis that greater levels of parental
overcontrol reduce children’s perceived competence, which in turn increases child anxiety levels.
Using a sample of 89 mother–child dyads (children aged 6–13), the authors conducted a mediation
analysis and found support for this model, i.e., child-perceived competence fully mediated the rela-
tionship between maternal overcontrol and child-reported worry symptoms. These data fit with the
theory that mothers perceived as using higher levels of overcontrolling behaviors (e.g., demanding to
know what the child is doing, not allowing the child to decide what they want to do) reduces children’s
perceived competence, which in turn increases their level of anxiety. Thus, overcontrolling parents
may increase levels of worry in their children through communicating that they do not have the skills
to successfully navigate challenges in their environment, which increases children’s tendency to worry
about their abilities. This increased worry likely leads to greater avoidance and subsequently reduced
opportunities for developing effective problem-solving skills. Future research into additional path-
ways through which parental behaviors or attachment styles impact worry is needed.
Assessment
Although there are many assessment tools for assessing the broad range of pediatric anxiety disorders,
few instruments focus exclusively on pediatric GAD. To date, seven measures designed to assess
worry and other symptoms of GAD have been published. Table 2 presents a description of each mea-
sure [15, 37, 39, 109–112].
The most widely used measure of child and adolescent worry is the Penn State Worry Questionnaire
for children PSWQ-C [37], a downward extension of the adult PSWQ [113]. The PSWQ-C assesses
the severity, excessiveness, and uncontrollability of worry in children and adolescents. Higher scores
reflect a greater degree of worry. Chorpita et al. [37] evaluated the psychometrics of the PSWQ-C in
a community sample of 199 and a clinical sample of 35 children and adolescents. They found that the
PSWQ-C consisted of a unitary factor (worry) and had high internal consistency with a = 0.89 when
samples were combined. High correlations with the worry scores of the Revised Children’s Manifest
Anxiety Scale (RCMAS; r = 0.71) and moderate correlations with the Children’s Depression Inventory
(CDI; r = 0.52) provided support for convergent validity. Further support comes from moderate to high
correlations with GAD items from the Anxiety Disorder Interview Schedule for DSM-IV Child/Parent
Version (ADIS-C/P), such as the number of worries (r = 0.56), intensity of worries (r = 0.72), and dis-
order severity ratings (r = 0.36). Chorpita et al. [37] reported a 1-week test–retest reliability for the
PSWQ-C of 0.92 in a clinical sample. Scores on the PSWQ-C have been shown to discriminate
between those children who meet criteria for a diagnosis of GAD and those meeting criteria for any
other anxiety or mood disorder [37].
Table 2 Assessment of pediatric GAD
Name of measure Reporter Age range (years) # of Items Response format Scoring/range Psychometrics
Penn State Worry Child (self-report) 6–18 14 Statements 0 (not true) to 3 (always true) Total score: a = 0.89
Questionnaire for 0–42
Children (PSWQ-C) [37]
The Worry Scale [109] Child (self-report) 5–18 31 Items 0 (never) to 2 (often) Total score: a = 0.93
0–62
Why Worry Questionnaire Child (self-report) 12–19 19 Items 1 (strongly disagree) to 5 Total score: a = 0.88
(WWQ) [110] (strongly agree) 19–95
Intolerance of Uncertainty Parent and child 7–17 27 Items 1 (not at all) to 5 (very much) Total score: a = 0.92 (child report),
Generalized Anxiety Disorder in Children and Adolescents
Scale for Children (self-report and 27–135 0.96 (parent report)

(IUSC) [111] parent report)
The Worry Scale for Child (self-report) 8–18 40 Items 1 (almost never) to 3 (often) Total score: a = 0.88
Children (WCS) [14] 40–120
Worry Interview [39] Child (interview) 5–12 3 Vignettes Open-ended Qualitative a = 0.70, k = 0.93
scoring
The Worry Interview for Child (interview) 6–16 14 Areas of worry Open-ended Qualitative k > 0.80, test–retest
Children (WIC) [112] Intensity of worry: 0 (none) scoring reliability = 0.78
to 4 (very, very much)
Frequency of worry: 0 (none)
to 2 (a lot)
81
The Worry Scale [109] assesses worries involving separation anxiety, contact with strangers,
meeting new people, future events, past events, physical symptoms, competency in school, social
relationships and social evaluation. Unlike the PSWQ-C, the Worry Scale inquires about specific
domains of worry and examines the frequency of those worries (never, often or always), not about the
excessiveness or uncontrollability of worry in general. The measure was developed and tested on
youth with anxiety, attention deficit hyperactivity disorder, and no disorders. The Worry Scale was
shown to have high internal consistency (a = 0.93) and good convergent validity, exemplified by posi-
tive correlations with self-report measures of child anxiety like the Revised Children’s Manifest
Anxiety Scale, especially the worry score (r = 0.72), State Trait Anxiety Inventory for children, espe-
cially trait anxiety (r = 0.66), and Fear Survey Schedule for Children-Revised version (r = 0.54). The
Worry Scale has been shown to differentiate between those children with an anxiety disorder and
those without. However, there is no evidence to conclude that the Worry Scale is able to differentiate
those children with GAD from those with other anxiety disorders.
Another self-report measure is the Why Worry Questionnaire (WWQ; [110]). It assesses erroneous
beliefs associated with worry. This questionnaire was created to investigate why, despite worrying
being a negative experience causing unpleasant effects, people continue to worry. Specific beliefs
associated with worry include, but are not limited to, guilt, distraction, psychological safety or protec-
tion, control, learning, and disappointment. Freeston et al. [110] found that these mapped onto two
factors: worries that help prevent negative events or avoid the worst outcome and worries that allowed
one to increase problem solving and to help find solutions. Unlike the previous self-report measures,
the WWQ does not inquire about specific worries or the intensity of those worries. The WWQ showed
good internal consistency (a = 0.88) in a sample of nonclinical youths (N = 777; 12–19 years of age)
and high convergent validity in being correlated with the PSWQ-C [78]. A revised version of the
WWQ, the WWQ-II, showed good internal consistency (a = 0.90) and high correlations with the
PSWQ-C in a sample of nonclinical students (N = 528; 79).
The Intolerance of Uncertainty Scale for Children (IUSC; [111]) was developed to measure a
child’s inability to cope with ambiguous and uncertain situations. It assesses a child’s tendency to
react negatively to uncertain situations across emotional, cognitive, and behavioral domains. Unlike
other measures, this questionnaire does not investigate worry itself, but a cognitive factor associated
with worry. In adult studies, the concept of intolerance of uncertainty (IU) has been proposed as a
cognitive vulnerability factor for excessive worry and GAD [114]. However less is known about the
relation between IU, worry, and GAD in children and adolescents. The IUSC comes as both a child
self-report and a parent report about child questionnaire. Both the child-report and the parent-report
versions show high internal consistencies (a = 0.92 and 0.96, respectively) and high convergent valid-
ity in being correlated with the PSWQ-C, Multidimensional Anxiety Scale for Children (MASC), and
Reassurance-Seeking Scale for Children (RSSC) in a sample of both nonreferred community children
(N = 124) and treatment-seeking anxiety-disordered children (N = 73). The IUSC is able to distinguish
anxiety-disordered youth from community youth, but there is no data to suggest it can differentiate
those youth with GAD from those youth with another anxiety disorder.
The final self-report measure is the Worry Scale for Children (WSC; [15]). Similar to the Worry
Scale, the WSC assesses the frequency of specific types of worries. Unlike the PSWQ-C and the
WWQ, it does not examine any accompanying cognitions or beliefs, or the severity and excessiveness
of such worries. Higher scores indicate greater levels of worry. The measure has shown high internal
consistency (a = 0.88) and convergent validity in a sample of 193 nonanxious children, but has not
been used with clinical samples.
In addition to child self-report questionnaires, two interview measures have been developed. The
first was developed by Vasey et al. [39]. During this interview, children read three vignettes depicting
worried children in typical situations. Children are then asked to provide items that the child in the
story could be worried about and then asked to elaborate on why that child would be worried about
that item. The responses are coded and yield scores relating to the frequency of worrisome thoughts
in each vignette, length of worrisome statements, and content of the worry. Content is coded as either
(1) relating to self, (2) relating to significant others, or (3) miscellaneous. Self-referential worries are
then broken down into (a) threats to physical well-being (e.g., injury, sickness, and kidnapping), (b)
threats to behavioral competence (e.g., not being able to complete one’s work), or (c) threats to social
evaluation (e.g., being teased or embarrassed) or psychological well-being (e.g., feelings of incompe-
tence). The measure was developed as a way to relate children’s worry to their social–cognitive devel-
opmental status. The measure has only been used with a community sample, and no data is available
determining whether this interview would be effective at screening worries of children with GAD.
Another interview, developed by Silverman et al. [112], the Worry Interview for Children (WIC) is
a semi-structured interview designed to assess worries in 14 areas: health, war, disasters, school, per-
formance, future events, personal harm, little things, family, friends, classmates, money, appearance,
and other worries not covered by the categories above. For each worry, children are asked to rate the
intensity of the worry on a five-point scale. Children are then asked to rate the frequency with which
they worry about that item. Each interview takes approximately 10 min to complete. The WIC has
shown to be a reliable interview (e.g., 1-week test–retest reliability was 0.78) and was able to dis-
criminate children with GAD from those with another anxiety disorder [13, 112].
Taken together, the above measures provide some options for assessing worry in children and ado-
lescents. Since not all measures of worry assess the same construct, the “best” instrument depends
largely on the goal of the assessment. For instance, if a measure is needed to screen for the diagnosis
of GAD, the best tool would be the PSWQ-C or the WIC. The WIC’s format provides in-depth infor-
mation about worry that cannot be gained from the use of a self-report questionnaire. For the purposes
of gathering data on the content of children’s worry (but not impairment, severity, or associated physi-
cal symptoms), the WIC, the Worry Scale, or the WSC would be appropriate.
Treatment
Evidence-based treatments for pediatric GAD parallel those for youth with other anxiety disorders,
discussed in the chapter “Cognitive-Behavioral Treatment for Pediatric Anxiety Disorders,” and
include cognitive behavioral therapy (CBT), selective serotonin reuptake inhibitors (SSRIs), or their
combination [115]. Data on the efficacy of CBT and medication are based on treatment studies that
have included samples of youth with any combination of GAD, SAD, and SOP rather than on youth
who present exclusively with GAD. The inclusion of these three anxiety disorders in most treatment
studies is due to the high rates of comorbidity both at the symptom and diagnostic level. Evidence
suggests that youth with each of these disorders respond to similar treatment strategies and the pres-
ence of GAD does not predict poorer treatment response or remission [116]. Only a small number of
randomized controlled medication trials have focused exclusively on youth with GAD. Recently,
preliminary data have been published on a pediatric adaptation of a GAD-specific CBT. These GAD-
specific treatment studies are briefly summarized below.
Pharmacological Studies
Initial trials for youth with GAD were small and evaluated sertraline [117]. Specifically, in a 9-week
double-blind placebo-controlled trial, 22 children, ages 5–17 years, were randomized to sertraline
(25–50 mg/day) or placebo. Youth receiving sertraline relative to placebo had significantly larger
reductions in anxiety symptoms (based on the Hamilton Anxiety Scale and the Clinical Global
Impression Improvement scales).
In a larger report, Rynn and colleagues [118] reported findings from two randomized, double-
blind, placebo-controlled trials with youth 6–17 years of age who met DSM-IV criteria for GAD.
Youth received a flexible dosage of extended-release venlafaxine (N = 157, 37.5–225 mg/day), a sero-
tonin-norepinephrine reuptake inhibitor or placebo (N = 163) for 8 weeks. Results were inconsistent
across the two studies with extended-release venlafaxine group showing statistically significant
improvements on the primary outcome (i.e., change in a composite score based on nine items from the
GAD section of a modified version of the Schedule for Affective Disorders and Schizophrenia for
School-Age Children) in study 1 but not in study 2. In a pooled analysis across the two studies, the
response rates, based on a CGI-I score of <3, were significantly greater with extended-release venla-
faxine than placebo (69 % versus 48 %). Treatment-emergent adverse events for venlafaxine that were
twice that of the placebo group included asthenia, pain, anorexia, and somnolence. Statistically
significant changes in height, weight, blood pressure, pulse, and cholesterol levels were observed in
the extended-release venlafaxine group. The authors concluded that the high placebo response rate,
particularly evident in study 2, contributed to its failure to show a statistical separation between
extended- release venlafaxine and placebo.
Hidalgo et al. [119] reviewed the pharmacological literature for both adults and children with
GAD. A total of 21 studies were found but only 2 were with youth and included SSRIs. The results
indicated that the average effect size (generally using the HAM-A) across all studies was 0.39 and
significantly higher effect sizes were found for children/adolescents than adults, i.e., the ES for
youth was 1.38 based on the findings of the two studies. Currently, SSRIs are considered the first-line
pharmacological treatment, as these medications have the fewest side effects and laboratory testing
is not indicated (see [120] for review).
CBT Studies
Few studies have examined a GAD-specific CBT protocol. Early reports of psychotherapy for youth
with GAD involved case studies [121, 122], and the treatment involved standard CBT strategies such
as those found in the Coping Cat [123]. Response rates were similar to those found in larger efficacy
trials examining CBT for other pediatric anxiety disorders. However, given that only 60 % of youth
respond to CBT, efforts at optimizing CBT are needed.
Toward this end, recent efforts aimed at adapting CBT specifically for GAD have been reported.
Leger et al. [70] modified a GAD-specific CBT treatment by Dugas et al. [124] and examined its
effect on older adolescents (16–18 years) with a primary diagnosis of DSM-IV GAD. The Dugas et al.
model of GAD [125] assumes that GAD is maintained by a number of cognitive factors including a
low tolerance for uncertainty, dysfunctional beliefs about worry, negative problem orientation, and
dysfunctional strategies to reduce distress (i.e., thought/image suppression, ruminating). Their GAD-
specific treatment, therefore, targets these factors and includes worry awareness training, planned
exposure to uncertainty, modification of dysfunctional beliefs about worry, and at post treatment
problem-solving training and relapse prevention. In an open trial of this treatment with a sample of 7
youth (an average of 13 sessions), 43 % no longer met diagnostic criteria for GAD at post treatment
[70]. Payne et al. [126] further modified this treatment, based on the work and recommendations of
Leger and colleagues [70]. The modification involved decreasing the didactic and increasing the expe-
riential components (via in session exposures), individualizing aspects of the treatment to age and matu-
rity level, and applying the treatment to younger ages. According to the authors, the treatment proceeded
in six stages: (1) worry awareness training, (2) planned exposure to uncertainty, (3) modification of
dysfunctional beliefs about worry, (4) modified problem-solving training, (5) imaginal exposure to
unpleasant images or worries, and (6) relapse prevention. In an open trial, 16 youths (7–17 years) with
a primary diagnosis of DSM-IV GAD were treated (average of 10 sessions, range was 5–15). All
participants who entered the study completed treatment and 13 (81 %) lost their GAD diagnosis (not
blindly assessed). Results were encouraging and await more rigorous scientific evaluation. In addi-
tion, comparisons between GAD-specific and “generic” CBT will be needed.
Case Follow-Up
Daniel’s treatment involved a combination of an SSRI and CBT. Specifically, he was started on a low
dose of sertraline (25 mg/day) that was titrated up to 200 mg/day over the course of 12 weeks without
side effects. Simultaneously, he completed a 12-week course of CBT. His CBT treatment began with
an overview of the CBT model (i.e., how anxiety can manifest itself somatically, behaviorally, and
cognitively), and he was asked to monitor these symptoms of anxiety and worry daily using a struc-
tured diary. He and his parents generated a list of situations that evoked worry and caused distress
and then developed a plan to begin both imaginal (initially) and in vivo exposures. To facilitate expo-
sure to these worry-provoking situations, he was taught how to examine and modify his worry thoughts
(to ones that are more realistic and helpful), to use relaxation strategies, and to employ problem-
solving skills. He applied these skills at night, at school, and while playing sports. His parents were
also informed about ways they could support his treatment and reduce anxiety-enhancing parenting
behaviors (e.g., providing excessive reassurance, accommodating avoidance). Over time, Daniel
experienced fewer somatic symptoms, was better able to “turn off” his worry, and improved relations
with his parents.
Summary
Though pediatric GAD is a relatively new diagnosis, the hallmark symptoms of the disorder (i.e.,
worry, somatic symptoms) have remained unchanged since DSM-III and the diagnosis of OAD.
Research on pediatric GAD has produced significant advances in our understanding of its prevalence,
presentation, and course. Assessment tools focused specifically on worry have facilitated this research.
Findings indicate that GAD is prevalent in about 3 % of the general population of youth, increases
with age, and presents similarly across gender and races/ethnicities. Early-onset GAD appears chronic
and confers risk for downstream disorders, most notable other anxiety disorders. Developmental mod-
els of GAD highlight that both biological and environmental factors contribute to illness onset and
maintenance. Future research evaluating additional components of these models is still needed.
Effective pharmacological and psychosocial treatments are available; however, there remains a dearth
of research examining psychosocial treatment options that specifically target worry and GAD.
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Pediatric Social Phobia
Vasco M. Lopes and Anne Marie Albano
Abstract Social phobia (SP) is a common psychological disorder characterized by excessive fear and
avoidance of social situations. With a typical onset in late childhood/early adolescence, its course is
chronic and unremitting if left untreated. SP has shown to have high psychiatric comorbidity, particu-
larly with depression and other anxiety disorders. Neuroimaging studies show hyperactivity in the
amygdala and prefrontal regions in response to social threat in children with social phobia. The past
decade has seen a significant increase in validated measures used to screen for and diagnose SP.
Effective treatments for pediatric SP include cognitive-behavioral therapy (CBT) and SSRI pharma-
cotherapy, either alone or in combination.
Keywords Social phobia • Social anxiety • Generalized social phobia • Performance anxiety
• Shyness • CBGT-A • SET-C
Case Scenario
Michael D., a 14-year-old high school sophomore, was brought to the clinic by his parents, mostly
against his wishes. The D’s sought treatment for Mike when he began refusing to attend school because
of a group presentation that was assigned in his social studies class. At the time of the intake, Mike
had missed 3 weeks of school. The D’s recognized that Mike’s school refusal was just a new way
of avoiding social attention, but were concerned that his behavior was now at a significant level of
dysfunction that required intervention.
Mrs. D. described a long history of “shyness” with Mike. As a baby, he was always attached
to one of his parents whenever there were visitors in the house or when the family went on outings.
It took Mike until he was nearly 4 years of age to warm up to and interact comfortably with relatives.
He had difficulty attending kindergarten and would often refuse to play with other children, although
he did make two good friends by second grade. As the boys grew older and enlarged their social
circles through middle school, Mike would drop out of activities and avoid social gatherings such as
V.M. Lopes
Department of Psychology, Fordham University, New York, NY, USA
A.M. Albano (*)
Department of Psychiatry, Columbia University Clinic for Anxiety and Related Disorders,
Columbia University, New York, NY, USA
e-mail: albanoa@nyspi.columbia.edu
92 V.M. Lopes and A.M. Albano
parties. Mike was always a good student, although he never volunteered to answer questions or
participate in class.
During the interview of Mike and his parents, it was evident that he had long-standing social phobia,
along with dysthymia, as he was acutely aware that “my life is passing me by.” In describing his
school refusal, Mike admitted to having intense fears of looking foolish in front of others, and despite
his good school performance, he felt the other kids were smarter than he. He admitted to feeling
intense fear in a number of social contexts, from informal conversation to performance situations,
such as oral reports. Mike’s interaction fears were affecting his ability to engage in conversation,
answer the telephone, and engage in typical teenage situations, such as dating.
According to the DSM-IV, social phobia (social anxiety disorder) is a marked fear of one or more
social or performance situations, where the person is exposed to unfamiliar people or evaluation from
others. The term “social anxiety” was added to the DSM-IV nomenclature to underscore the distinc-
tion between social phobia, which can produce fear of one or many social situations, and specific
phobias, in which the child or adolescent has excessive fear of only one particular stimulus. Commonly
feared situations in social phobia include initiating conversation with peers, speaking or performing
in front of the class, and attending social gatherings, such as play dates, dances, or parties, in which
the child is expected to interact with others.
Upon exposure to the feared social or performance situation, the child with social phobia (SP) may
exhibit physiological symptoms of anxiety, such as increased heart rate, blushing, lightheadedness,
gastrointestinal distress, or trembling. At times, these symptoms may result in full or limited symptom
cued panic attacks. In children specifically, anxiety reactions may also manifest in the form of crying,
tantrums, shrinking away from others, or refusing to speak. Whenever possible, the child will attempt
to avoid the social or performance situation that prompts the anxiety, and if unavoidable, the situation
may be endured with intense distress (e.g., “Let me just get through this!”). The avoidance, anxious
anticipation, and/or emotional distress experienced during the social or performance situation
significantly disrupts academic, family, occupational, and social functioning.
Generalized Versus Non-generalized Subtypes
Currently, in DSM-IV, generalized subtype is designated if the child fears “most social situations”;
otherwise, a diagnosis of SP is assigned with no subtype indicated. However, it has become common
practice in the literature to indicate non-generalized when the child fears only one social situation
(e.g., public speaking), or a few contextually similar social situations (e.g., test taking, other evalua-
tive situations such as performing in gym class). Of note, this dichotomous conceptualization of SP as
“generalized” versus “non-generalized” has been heavily debated and scrutinized. Some argue that
the generalized subtype has significant value and utility since these children usually have greater
severity and impairment, higher likelihood of comorbidity, and worse prognosis than those with
non-generalized SP [1–5]. Others suggest that this specification has poor reliability and an unclear
operational definition since the DSM does not specify how many social fears must be present in order
to reach the threshold of generalized subtype [6]. Despite this controversy, and the fact that a non-
generalized subtype is not specified in DSM-IV, these subtypes will be noted throughout this chapter
when necessary to accurately reflect research findings.
Pediatric Social Phobia 93
DSM-5 Proposed Description
The proposed DSM-5 criteria for social phobia are not expected to deviate much from the DSM-IV.
One proposed change, however, lies in the name of the disorder, itself. Whereas the disorder was
termed “Social Phobia (Social Anxiety Disorder)” in DSM-IV, it will be called “Social Anxiety
Disorder (Social Phobia)” in DSM-5. This semantic change is proposed to reflect the evidence that
most individuals with this disorder exhibit anxiety that is generalized to many social situations, and
not to one specific situation, as the name phobia implies.
In DSM-5, SP will continue to be characterized by the marked fear of one or more social situations
in which the person may be evaluated or scrutinized by others. According to Bogels et al. [6], in effort
to better organize the Criterion A symptom of “fear or anxiety in social situations,” social situations will be
classified into one of three categories: interacting with others (i.e., having a conversation), being observed
by others (i.e., eating), or performing in front of others (i.e., giving a speech). Additionally, whereas
DSM-IV only contains one specification (generalized subtype), DSM-5 will likely carry three specifications:
generalized, performance only, and selective mutism (SM). The specification of performance only has
been added to reflect evidence that performance anxiety, the excessive fear of performing in front of
an audience (i.e., giving public speeches, an artistic performance, or presentation), is a qualitatively
distinct type of SP [6]. Selective mutism (SM), formerly its own diagnosis under DSM-IV, will be
designated as a subtype of SP in DSM-5. Typically diagnosed in young children, SM is described
as the failure to speak in settings where speech is socially expected (i.e., school), despite normal
language ability. The rationale for including SM as a specific type of SP comes from research indicating
significant comorbidity and conceptual overlap between the two disorders [7–9] (see Chap. 11 for
more information on SM). Additional changes to the DSM-IV social phobia criteria have been
proposed that only impact adults with the disorder; therefore, they will not be discussed here.
Prevalence
Epidemiological surveys consistently find that SP is one of the most commonly occurring mental
disorders [2], with child and adolescent prevalence ranging from 5 % to 13 % [10, 11]. According to
the National Comorbidity Survey Replication-Adolescent (NCSR-A; 3), 8.6 % of children, ages
13–18 years, meet criteria for SP at some point during their lifetime. Adult prevalence rates are similar
[4, 5, 12], suggesting that SP is a chronic and unremitting disorder if not treated [2]. Research consis-
tently demonstrates that the majority of individuals with SP are diagnosed with the generalized
subtype [5]. In an epidemiological study, Burstein et al. [3] showed that 55.8 % of children and ado-
lescents diagnosed with SP met criteria for the generalized subtype, while 44.2 % met criteria for
non-generalized, and only 0.7 % met criteria for the proposed DSM-5 performance-only subtype. This
proportion of generalized subtype is similar to that of adults [4]. Across studies, subtype prevalence
estimates vary, however, depending on how generalized SP is operationally defined and the assessment
instruments used [4].
In children and adolescents, female prevalence of SP is nearly twice that of males [13]. Age of onset
is typically in adolescence, with studies reporting an age range of 12–16 years [5, 13–15]. Age of onset is
dependent on several factors, however, such as gender and subtype. Females are more likely to develop
the disorder in childhood or adolescence than males (9.2 % and 7.9 % lifetime prevalence, respectively)
[3]. Further, within the adolescent period, onset is significantly earlier for females, with an average age of
onset being 11.5 years, compared to 14 years of age for males [5]. Children diagnosed with the general-
ized subtype are more likely to have an earlier age of onset [3, 4]. Roughly 50 % of generalized SP chil-
dren are diagnosed before age 12, compared to only 19 % of non-generalized SP [5].
Course
The risk for being diagnosed with SP increases dramatically during late childhood and early adolescence.
Throughout adolescent development, this risk continues to rise, although not nearly at the same rate
as observed during late childhood. Once the individual reaches young adulthood (age 25), the risk of
developing SP decreases dramatically [5]. In other words, if the child has not shown significant social
anxiety during adolescence, his/her odds of developing symptoms in early adulthood are low.
When SP symptoms emerge during adolescence, they are typically chronic and unabated [2]. If left
untreated, an adolescent’s anxiety and avoidance of social situations will typically maintain or exac-
erbate throughout their development into early adulthood in an unremitting manner. Evidence
suggests that only 20–40 % of individuals with SP will show remission within 20 years of onset [16].
This chronic nature is compounded by the fact that few adolescents seek treatment for SP. Research
shows that only 12.1 % of adolescents diagnosed with SP receive treatment for the disorder [17]. This rate
is much lower than the 68 % of adults with lifetime SP who eventually seek treatment [4]. This failure
to seek treatment for adolescents with social phobia may be partially due to an unwise and unwar-
ranted idea that social phobia is a “medicalization” of shyness geared towards promoting treatment
with pharmaceutical agents, an idea often portrayed in the popular press and media [e.g., 18]. Across
development, the likelihood of receiving treatment increases with severity as well as comorbidity [4, 17].
However, although individuals with high severity and comorbidity are more inclined to receive
general treatment, they are less likely to receive treatment specific to SP. In fact, retrospective analysis
of SP treatment utilization demonstrates that SP adults show an inverse relationship between number
of social fears and SP-specific treatment—those with a greater number of fears, severity, and comor-
bidity were less likely in their lifetime to receive therapy specific to their SP symptoms than those with
a smaller number of fears and lower severity [4]. The authors discuss the possibility that those with
severe SP may regard their social anxiety as a fixed part of their personality (i.e., shyness) that cannot
be changed. Although it is unclear whether these treatment-utilization patterns apply to adolescents,
the authors recommend that health care providers screen for possible SP when other anxiety, depressive,
or substance abuse symptoms are present.
In comparison to adults, adolescents’ symptoms are less likely to wax and wane over time, since
they have less control over choosing a niche accommodating to their social anxiety (i.e., a job with no
public speaking requirements). Children have much less control over their environment and are thus
less able to avoid anxiety-provoking social situations without consequence. Also, whereas adults with
SP may be beyond a certain social life stage that previously brought on tremendous anxiety (i.e., a
person with romantic relationship anxiety gets married and no longer needs to date), late childhood/
early adolescence is marked by a tremendous increase in social demands, such as expanding social
groups in school, extracurricular activities, and dating. The fact that children cannot control their
environmental niches, coupled with the increase in social demands, causes social anxiety to be chronic
and stable throughout this life period.
Comorbidity
SP has a high incidence of comorbid psychiatric disorders in children and adolescents, with epidemio-
logical studies showing rates from 59 % [19] to over 71 % [5]. Childhood SP co-occurs most fre-
quently with other anxiety and mood disorders and more moderately with oppositional defiant disorder
(ODD) and later substance use [3]. Comorbidity with other anxiety disorders ranges from 20 % to
41 % [3, 19], with agoraphobia, generalized anxiety, and separation anxiety yielding the highest rates
of comorbidity (32.4 %, 32 %, and 27.4 %, respectively) [3]. Comorbidity of SP with mood disorders,
including depression and dysthymia, ranges from 41 % to just over 50 % [19–22].
Notably, the generalized subtype of SP is associated with significantly higher comorbidity rates
than non-generalized [3, 5, 20], with some studies suggesting rates as high as 88 % [10]. Consistent
with this, the risk of developing comorbid disorders is more likely with increased number of social
fears. For example, Ruscio et al. [8] conducted an epidemiological study with SP adults investigating
a number of social fears. Although this is not the standard manner of differentiating generalized versus
non-generalized SP in the DSM, the investigators operationally defined non-generalized SP as having
four or fewer social fears and generalized SP as eight or more social fears. The investigators indicate
that lifetime SP comorbidity with other disorders is 62.9 % for non-generalized and 81.5 % for gen-
eralized SP. Their results are consistent with previous findings indicating a linear effect between
number of social fears and likelihood of comorbidity—the greater number of social fears, the higher
the likelihood of manifesting comorbid disorders [22].
SP has been described as a temporally primary condition, since it has consistently been shown to
have an earlier age of onset than comorbid conditions [5]. Although the causal mechanism of this
developmental trajectory is unclear, it highlights the implications for early identification and treatment
of SP in the prevention of secondary disorders [22]. In retrospective studies of SP adult comorbidity,
in 59–76 % of cases, onset of SP precedes the initial onset of depression [20]. Longitudinal prospec-
tive studies of adolescents and young adults with SP indicate that carrying an SP diagnosis causes a
two-fold increase in risk for developing later depression, with those diagnosed with the generalized
subtype showing an even greater risk [20]. As a result of this temporal pattern, adolescent comorbidity
is typically lower than in adults [5, 19, 21], since SP symptoms, themselves, are starting to manifest
during this age range, and comorbid disorders, such as depression, substance use, and other anxiety
disorders, typically develop later [4, 5].
The high comorbidity between SP and depression has received considerable research attention
[20, 22, 23]. Recent epidemiological research investigating adolescent comorbidity [3] suggests that
the risk for depression and alcohol use in adolescents with SP is not nearly as high once other anxiety
and behavioral disorders are factored out. This suggests that SP alone does not predict the later onset
of depression but, instead, does so along with multiple anxiety disorders and disruptive behaviors in
combination. In other words, the greater severity of overall psychopathology, the greater likelihood of
manifesting secondary depression and alcohol use. The authors discuss, however, that this new finding
may stem from the fact that epidemiological data was being collected on the current functioning of
adolescents and not retrospective functioning of adults. This raises the possibility that secondary
depression and alcohol use is more likely to occur in late adolescence/early adulthood, meaning that
only retrospective studies or studies with early adults would be able to capture this onset.
In the last decade, much criticism has come from the media and popular press about how the mental
health field has pathologized shyness [i.e., 18], a normally developing trait, into the psychiatric disor-
der of social phobia. Recently investigators have been interested in how much overlap occurs between
the normative temperamental trait of shyness and social phobia. Research has found that whereas
46.7 % of adolescents and 62.4 % of parents surveyed in the NCSR-A rated the adolescents as “shy,”
only 10–12 % of parents or self-identified “shy” youth also met criteria for social phobia [24].
Adolescents with social phobia were no more likely than their shy peers to be taking medication
for the disorder, despite significantly greater impairment in their ability to function in school, work,
or everyday life situations, and the presence of serious psychiatric comorbidities including other
anxiety disorders, depression, and substance abuse. Thus, although shy children exhibit difficulty in
novel social situations, it is considered normative, and the child’s slight difficulty and fears usually
subside after a short duration. Social phobia, on the other hand, is associated with much greater distress
and long-standing impairment in various domains of functioning, as well as increased psychiatric

comorbidity.
The hallmark of SP is the exaggerated fear and avoidance of social situations in which the person
is subject to public evaluation and scrutiny. Several other disorders show similar avoidance responses
to social situations—but it is the reason for their avoidance that marks the distinction between SP and
other DSM conditions.
Separation anxiety disorder involves a developmentally inappropriate fear of being separated from
one’s parent or caretaker. Children with separation anxiety may present with symptoms in social
situations similar to that of SP; however, their underlying fear, avoidance, or tantrums stem from
being separated from their caregiver rather than being evaluated by or fearing rejection of others.
When the parent or caregiver is present, a child with separation anxiety disorder can function in social
situations comfortably. A child with SP, however, will experience discomfort and anxiety in feared
social situations, even if the parent is present.
In panic disorder with agoraphobia the individual fears the consequences of a panic attack, which
mostly are misinterpreted as a heart attack, stroke, or other catastrophic bodily concern. Additionally,
it is characterized by a fear of having another panic attack and avoidance of situations where potential
panic attacks may occur. Although children with SP may also experience significant physiological
symptoms of anxiety (i.e., blushing, sweating, or increased heart rate), they do not misinterpret these
symptoms as life-threatening or create catastrophic interpretations of these bodily cues. Thus, although
panic attacks may be present in both panic disorder and SP, the ultimate fear and avoidance in panic
disorder stem from the fear of being helpless with symptoms or even dying. In SP, on the other hand,
the child may avoid situations in which they are likely to blush or have trouble breathing due to fear
of embarrassment or negative evaluation from others. In agoraphobia without history of panic attacks,
the child has a pervasive fear and avoidance of situations where they may develop subthreshold panic-like
somatic symptoms (i.e., headache, vomiting, cardiac symptoms, loss of bladder control). The child’s
main fear is not necessarily the resulting social evaluation of their symptoms but the presumed lack
of ability to get help in managing the physiological symptoms.
There is overlap between SP and avoidant personality disorder (APD). This is evidenced by high
comorbidity as well as conceptual similarities. APD has been suggested to be a more severe form
of generalized SP, rather than a qualitatively distinct disorder [25, 26]. A key distinction lies in perva-
siveness. Adolescents with SP can become highly anxious and avoidant of certain social situations yet
have a healthy sense of adequacy in other social domains. Adolescents with APD have an underlying
sense of inadequacy and ubiquitous preoccupation with being criticized by others, resulting in avoid-
ance of most situations that require social interaction. Although differentiating between APD and
non-generalized SP may be more clear, it becomes tricky when the adolescent fears so many social
situations, as in the case of generalized SP, that it seems related to an underlying ubiquitous sense of
inadequacy in succeeding in social situations commonly seen in APD. In the case of this severe form
of generalized SP, it may be useful to provide both diagnoses in order to highlight the severity of
social impairment. It is also important to note that the assignment of an Axis II diagnosis of personality
disorder remains controversial, as it is often proposed that children and adolescents do not yet have
the timeline and stability in presentation to warrant a characterological disorder [27].
In addition to disordered functional communication and restricted interests, children with pervasive
developmental disorder (PDD) or autism spectrum disorder (ASD) often avoid social situations,
instead preferring solitary activities. This avoidance of social interaction is not necessarily caused by
fear but rather is a consequence of an inherent lack of interest in social interaction. Although some
ASD children gain a desire for social interaction as they develop, their deficient social skills limit their
chances of developing successful social relationships [28], and they may become the target of bullying
[29]. As a result of their continued social rejection and peer victimization, children with ASD often
develop significant anxiety in social situations [30]. Since this anxiety results from actual rejection
and is not exaggerated, an SP diagnosis is unwarranted. Despite this nosological feature, it should be
noted that children with ASD are likely to require treatment specific to social anxiety, especially those
who experience high physiological arousal to stressful situations along with poor social skills relative
to other ASD children [31].
The differential between SP and a depressive disorder can be challenging in light of the high
comorbidity between the two, as described above. When differentiating between these two disorders,
it is important to understand the different patterns in behavioral withdrawal and mood symptoms.
First, there is a difference between the avoidance of social situations that is a hallmark of SP and the
diminished interests common to depressive disorder. Although children with SP may seemingly lose
interest in activities, their avoidance is circumscribed to social activities only, while other interests
(i.e., games, movies, playing with toys) remain unaffected. A loss of pleasure and diminished interest
in all or most activities (which may include social interaction), on the other hand, are more consistent
with symptoms of a depressive disorder. Second, although children with SP may show significant
mood symptoms, such as withdrawal, agitation, irritability, crying, and tantrums, these behaviors
occur almost exclusively when they are forced into social situations that increase their anxiety. When
SP children are not immersed in social situations that cause emotional distress, they are able to function
normally. Depressive children, on the other hand, are more likely to experience more persistent and
chronic mood symptoms that are either dispositional or in response to many environmental antecedents,
but not fear of social situations alone.
Etiology
The origins of social phobia have been studied from various perspectives. Although genetic and bio-
logical influences have been shown, social and environmental factors have also been linked to the
manifestation and maintenance of SP.
Genetics
Although the research in this area has been sparse, kinship studies suggest that genetics have a mild
to moderate effect on the development of SP. Research indicates that parents with SP are more likely
to have children who develop SP than non-affected parents [32]. Twin studies have estimated that the
heritability of social anxiety ranges from as low as 0.10 [33] to as high as 0.60 [34], suggesting that
genetic influences account for 10–60 % of the variance in the development of social anxiety. Although
these discrepant findings suggest an inconclusive genetic effect, a meta-analytic review of SP twin
studies reveals that the genetic influence of social anxiety increases as the child gets older [35]. This
suggests that the phenotypic expression of social anxiety increases as the child develops into an age
where social relationships become more predominant. In other words, as a child who is genetically
predisposed to develop social anxiety becomes an adolescent, and social relationships become more
important, the greater the likelihood of phenotypically manifesting socially anxious traits.
Temperament
Longitudinal studies of biological disposition towards developing social anxiety have been conducted.
Most of this research has investigated infant temperamental styles, tracking these children over time
to determine if certain temperamental styles are associated with SP. In particular, investigators have
been interested in how the behavioral inhibition (BI) temperament style may lead to social anxiety.
BI is characterized as a consistently anxious disposition, with an exaggerated physiological response
to distress, constant hypervigilant attention, and behavioral avoidance in novel situations [36; see
Chap. 3 for a more detailed description of BI]. In studying infants with and without BI temperament
over time, those with BI are significantly more likely to develop SP in early adolescence [37], but not
other childhood anxiety disorders [38], suggesting that BI has good discriminative ability in identifying
children at risk for later SP.
Neurobiology
The amygdala plays a prominent role in detection of threat and processing fearful and salient stimuli
in the environment [39]. Thus, this key region has been the focus of much neuroimaging research in
anxiety disorders including social phobia. As most of this research has been conducted on adults,
these are the studies that will be reviewed here. Studies of pediatric SP will be included wherever
possible; see Chaps. 1 and 2 for more details of amygdala involvement in fear processing and in
pathology across anxiety disorders, respectively.
Research with adults has consistently shown a link between social anxiety and amygdala functioning
with greater amygdala responsivity associated with more generalized and severe social anxiety [39–42].
In these studies, researchers have focused primarily on amygdala responses to pictures of angry or
harsh faces that may be particularly salient to adults with SP because they can elicit an interpretation
of social rejection or disapproval. Results demonstrate a significant relationship between SP and
heightened amygdala reaction in response to viewing these facial expressions [41]. This relationship
is so robust that individuals with SP even show a heightened amygdala reaction to schematic line-
drawn harsh faces [40]. However, increased amygdala responsivity is not limited to viewing harsh
facial expressions; it has also been observed in response to other socially threatening stimuli, such as
experiencing negative cognitions [43], receiving negative evaluation from others [44], and the antici-
pation of giving a public speech [45]. Diagnostically, SP is characterized by increased sensitivity to
socially threatening cues, but not necessarily to cues unrelated to social situations. This has been sup-
ported by neuroimaging studies. For example, adults with SP show significant amygdala hyperactivity
in response to harsh facial expressions, but not to other threatening cues, such as violent pictures [46].
Amygdala responses to fearful faces have even been able to discriminate between generalized SP and
generalized anxiety disorder (GAD) [47], with adults with SP showing significantly greater amygdala
activity than those with GAD.
Recent neurobiological models of anxiety, including social anxiety, posit alterations in the prefrontal
cortex (PFC) as well as the amygdala. The PFC has been implicated in the regulation of emotion [48, 49],
and the circuitry between the amygdala and the PFC has been associated with conditioning of fear
responses [50]. BI models of anxiety suggest that individuals who are highly inhibited are hypersensi-
tive to fear conditioning, or become conditioned to feared stimuli too easily [51]. This model suggests
that circuits between the amygdala and PFC are hyperresponsive—such that when an anxious indi-
vidual experiences an ambiguous or potentially threatening cue, it leads to overactivity in this circuit,
which results in a fear response and behavioral inhibition. In support of this model, adults with SP
demonstrate alterations in prefrontal function underlying emotion regulation. For example, when
asked to engage in a cognitive emotion regulation strategy such as relabeling negative self-beliefs, SP
adults show insufficient activation and delayed onset of amygdala activity [44]. Similarly, when
shown harsh facial expressions and asked to conduct cognitive-linguistic strategies to cope with this
threatening cue, adults with SP show reduced activity in the amygdala and dorsolateral and dorsome-
dial PFC, as compared to controls [46]. Both of these studies suggest that, when required to regulate
their negative emotionality after exposure to social threat, SP adults have deficient neural functioning,
both in the amygdala as well as the circuitry between the amygdala and regions of the PFC implicated
in the downregulation of emotion.
Critical developmental changes that occur in the PFC during puberty such as increased axonal
myelination and synaptic pruning may play a specific role in the onset of social phobia during adoles-
cence. These neurological changes may result in increased metacognition, causing the early adolescent
to gain increased awareness and focused attention to how he/she is evaluated by others during a time
when social demands increase, likely leading to the onset of social anxiety. Evidence supports the role
of the PFC in response to social threats, particularly in socially anxious individuals. For example,
adults with generalized SP show increased activity in the medial PFC compared to controls when
presented with negative evaluative comments from others [43]. In a unique study, Guyer et al. [52]
used a novel “chat room task” to investigate the amygdala-PFC circuitry of adolescents with social
anxiety. Socially anxious adolescents and non-anxious comparisons were asked to rank 40 pictures of
peers based on their desirability to chat with them. Subjects were informed that they would be able to
chat with the peers whom they ranked the highest and that these peers would be aware of how they
were ranked. Two weeks later, during an fMRI scan, subjects were asked to rate the likelihood of
peers wanting to chat with them. This procedure was thought to elicit fear of social evaluation since
other peers “knew” how they were ranked by each subject. Results from this study indicated that,
compared to non-anxious comparisons, when looking at pictures of undesirable peers, adolescents
with social anxiety exhibited increased coactivation in the amygdala and ventrolateral PFC (vlPFC).
Blair et al. [53] investigated the neural functioning of adolescents with SP and compared these neural
patterns to those of SP adults, in a cross-sectional design. In this study, blood-oxygen-level-dependent
(BOLD) contrast responses were compared for 39 SP subjects (25 adults; 14 adolescents) and 39 controls
while viewing angry, fearful, and neutral facial expressions. Results indicated that both the adolescent and
adult SP subjects showed higher activity than controls in both the amygdala and the rostral anterior cin-
gulate cortex when viewing angry and fearful faces. Although longitudinal research is needed on the
developmental trajectory of pathological neural regions, this suggests that neural deficits in SP are similar
in adolescence and adulthood.
Clearly, additional research is needed to elucidate these neuroimaging findings in adults, as well as
to replicate them with children and adolescents, since these brain circuits are just starting to mature
and reorganize during this developmental period [49].
Environment/Parenting
Social phobia is characterized by cognitive biases about social situations; therefore, researchers have
been interested in the environmental source of these cognitions, particularly in youth. Parenting style
has been significantly linked with the development of anxiety and mood disorders in children [54],
including SP. Research suggests that an overprotective parenting style is a risk factor for developing
SP in children [55, 56]. Evidence also suggests that parenting style can discriminate between disor-
ders. Specifically, parental rejection leads to child depression, and overprotection leads to onset and
maintenance of generalized and social anxiety [57].
In a study of families of adolescents, Lieb et al. [32] found that adolescents with SP were
significantly more likely to experience rejection and overprotection from parents, even after control-
ling for parental psychopathology. Laboratory tasks of fathers and their children working together
to complete an origami task [58] showed that, after controlling for paternal depression and general
anxiety, fathers of children with high social anxiety were significantly more controlling than fathers
of non-anxious children, although these groups did not differ on other parenting behaviors, such as
rejection. Studies investigating adult retrospective self-report of parental style during childhood and
adolescence show that those with higher social anxiety rated their parents as much more overprotective,
controlling, and less warm than adults with lower social anxiety [55]. Retrospective accounts of
parental overprotection are associated with lower social responsiveness in a concurrent social interaction
laboratory task in adults with generalized SP, but not normally functioning adults [56].
Rather than children with SP being passive agents of their parents’ overprotection, some models
suggest a reciprocal relationship between the child’s behavioral inhibition and the parent’s assertion
of control [59]. Since socially anxious children may demonstrate chronic apprehension and reticence
in social situations, it may pull for protection and decision-making behaviors from the parent. This
protective behavior can lead to a vicious cycle of child anxiety and self-perceived inadequacy, since
parents are preventing the child from entering “risky” social situations, where they could otherwise
practice skills and disconfirm cognitive biases.
Peer Victimization
Since bullying has become a prominent topic in child development and in the popular press, researchers
have attempted to investigate negative developmental outcomes as a result of experiencing chronic
peer victimization. In community-based studies, as well as in studies of SP adolescents, findings have
consistently shown that children who are victims of bullying are at increased risk of developing social
anxiety [60–62]. Children and adolescents who experience multiple types of peer victimization,
including overt, relational, and reputational aggression, are at increased risk of developing fears of
negative evaluation, physiological symptoms of anxiety, and social avoidance [63]. Erath et al. [64]
indicate that not only do socially anxious children experience high peer victimization, they also expe-
rience chronically low peer acceptance in general.
Since studies have repeatedly shown that children with social anxiety are more vulnerable to being
victimized, researchers have wondered about the reciprocal nature of social anxiety and chronic peer
victimization [59]. In other words, does victimization cause SP, or do SP deficits cause peer victimiza-
tion? Research suggests that SP children possess inherent deficits in social skills [64, 65]; thus, some
investigators argue for the possibility these children’s anxious behaviors during, and avoidance of,
social situations increase their susceptibility to being victimized by peers. Whether the poor social
skills demonstrated by SP children are an inherent deficit or failure to perform is debatable, however,
and some researchers argue that children with SP do possess adequate social skills but inhibit their
appropriate response when in anxiety-provoking social situations [66]. Despite this debate, research
repeatedly demonstrates a strong relationship between SP and peer victimization; regardless of which
variable is temporally primary, the continuous peer rejection seen in SP can easily create a vicious
cycle and exacerbate social anxiety throughout the child’s development.
Cognitive-Behavioral
Rapee and Heimburg [57] propose a cognitive-behavioral model of the etiology and maintaining fac-
tors of SP. Here, they assert that one of the first key cognitive elements inherent in SP is the distorted
assumption that people are often critical and prone to evaluate others negatively. The individual also
possesses the belief that it is highly important to please and be positively appraised by others. When
the individual with SP evaluates the feared social situation, they form mental representations of them-
selves in the situation. These mental representations are theorized to involve two components: men-
tally encountering themselves as perceived by their “audience,” or other individuals involved in the
social situation, and mentally picturing their audience and especially their social cues that indicate
negative evaluation. This model holds that the individual’s level of social anxiety will depend on
the discrepancy between the expectation of others about social performance and the individual’s
evaluation of his/her actual performance. Given the notion that individuals with SP have irrational
beliefs about others’ perfectionistic expectations in social situations and that they are likely to be
overly critical about their own social performance, it creates a high likelihood for experiencing
significant anxiety in that social situation. Thus, when the individual enters that social situation, they
will do so with heightened anxiety, including associated physiological and behavioral features, such
as heavy breathing, increased heart rate, sweating, blushing, and freezing. These features lead to addi-
tional mental representations of what their audience must think of them and even more scrutiny in
looking for indicators of negative evaluation, which at this point, may be evident since the individual
may be showing overt signs of anxiety. This causes the individual to further criticize his/her perfor-
mance, causing more distress and a vicious cycle of anxiety.
Biopsychosocial Model
A comprehensive biopsychosocial model of social phobia has been proposed that brings together
many of these individual risk factors. Rapee and Spence [67] propose that the manifestation of SP
results from an interaction of genetic and environmental influences, such that individuals may have a
genetic predisposition to feel a certain level of anxiety in their social environment, a term they refer
to as “set point” (Fig. 1). This set point may be altered, either up or down, depending on the environ-
ment. According to this theory, children with a high genetically predisposed set point will require only
a low intensity of negative environmental influences necessary in order to manifest SP, whereas chil-
dren with a low set point will require much greater negative influences to manifest the disorder.
Negative environments that increase this set point include overcontrolling parenting and peer victim-
ization, while other factors, such as pro-social peer relationships, may be protective and lower the
child’s set point [63].
Detweiler et al. [68] go further than Rapee and Spence and propose additional influences of neuro-
biological and developmental factors (i.e., temperament, attachment). They propose that the increase
of social anxiety seen in early adolescence is a result of the tremendous increase in social demands
typical of this age range that occur simultaneously with changes in PFC function that allow for
increased self-reflection, as discussed earlier. As a result, the early adolescent places greater significance
on evaluation from others than he/she did during childhood. Although most adolescents show a nor-
mative increase in social fears during this time, those with biological and developmental vulnerabili-
ties for SP will enter this social-developmental period with significant difficulty. Moreover, Detweiler
et al. [68] discuss that not only does the child’s family and social environment influence his/her mani-
festation of social anxiety but his/her inherently inhibited style can influence the way that others
respond socially, in a reciprocal interaction.
Assessment
The measurement of childhood social anxiety has shown great improvement over the past decade.
Today, there are several assessment options when childhood SP is in question, including broad anxiety
rating scales for screening, rating scales specific to childhood SP, structured diagnostic interviews for
determining diagnosis, and behavioral assessments to observe symptoms during an anxiety-provok-
ing situation. This section will describe several assessment tools used specifically to evaluate social
phobia symptoms in children.
Fig. 1 A model of the development of social phobia (from Rapee [67]; used with permission)
Social Anxiety Rating Scales
Rating scales have been developed to specifically assess the severity of social anxiety symptoms
across different social domains. These offer parent-report as well as self-report versions which is
particularly important in light of the SP child’s inherent tendency to respond in a way that pleases
others [69]. Especially when using self-report rating scales to monitor treatment progress, one must
be mindful that the SP child’s rating may not be reliable, since they may respond favorably out of fear
that the clinician will evaluate them negatively if they do not show progress.
The Social Anxiety Scale for Children-Revised (SASC-R) [70] was developed to measure SP in
children ages 6–13; the SAS-Adolescent version can be used to assess older children, ages of 13–18.
Parent-report versions are available in addition to self-reports. Both versions consist of 22 items, on a
5-point scale (not at all—all the time), and are composed of three subscales as well as a total score.
The three subscales, derived from factor analysis, include fear of negative evaluation from peers,
social avoidance and distress specific to new situations, and generalized social avoidance and distress.
The SASC-R has shown adequate internal consistency, test-retest reliability, and construct and dis-
criminative validity [71]. It also shows good sensitivity to clinical levels of social anxiety. A total
score of 50 or higher suggests a possible diagnosis of SP.
The Social Phobia and Anxiety Inventory for Children (SPAI-C) [72] has also shown to be useful
in measuring childhood SP. This scale assesses children ages 8–14 and includes a parent version [73].
The SPAI-C is composed of 26 items, on a 4-point scale (0–3; never or hardly ever-always), and con-
tains five subscales: assertiveness, general conversation, physical and cognitive symptoms, avoidance,
and public performance. This scale shows adequate internal consistency, test-retest reliability, and
construct validity [71]. It also shows good sensitivity to clinical levels of social anxiety. A total score
of 18 or higher (out of a possible 52) suggests a diagnosis of SP.
The Liebowitz Social Anxiety Scale for Children and Adolescents (LSAS-CA) [74] is a clinician-
based rating scale that measures SP in children ages 7–18. The LSAS-CA consists of 24 items with
separate ratings of anxiety and avoidance on a 4-point scale for each item. In addition to a total score,
two subscales are derived: social interaction situations and performance situations. Separate anxiety
and avoidance levels for each subscale can also be obtained. Psychometric properties, including inter-
nal consistency, test-retest reliability, and construct validity, are all adequate [74]. A total score of 22.5
or higher suggests possible clinical levels of SP.
Behavioral Assessments
Behavioral assessments or behavioral approach tasks (BATs) are useful for clinicians to gather infor-
mation about the child’s functioning in a specifically feared situation (i.e., speaking with a strange peer).
Although parent and child ratings provide information about social anxiety severity, children may not
always have good insight about their socially anxious behaviors in specific situations, especially if
they are chronically avoiding these situations, and parents may not have the opportunity to observe
their child in certain social domains (i.e., socializing at school). Thus, BATs allow the clinician to
observe and code for behaviors in a specific situation in a manner that allows for development of treat-
ment goals and monitoring progress of social anxiety reduction and skill acquisition.
The Social Performance Rating Scale (SPRS) [75] is a tool used for observing and coding the target
child’s social behavior while holding a one-on-one conversation with another person. The clinician
codes for specific behaviors on a 1- to 5-point scale, such as eye gaze, vocal quality, length of conver-
sation, discomfort exhibited (i.e., fidgetiness, throat clearing, stuttering, or giggling), and conversa-
tion flow (i.e., initiating conversation, awkward pauses, maintaining conversation). The SPRS has
shown high inter-rater reliability, acceptable internal consistency, and good discriminative validity.
The SPRS, as well as other BATs, has several limitations, however. First, they require a lot of training
in order to reliably code for specific behaviors, making the real-world application of this assessment
challenging. Second, assessment is restricted to one specific social domain and does not measure
other social fears. Thus, although the clinician will have fruitful information about the intensity and
quality of social anxiety in one specific domain, the BAT does not answer questions about the breadth
of the child’s other social fears, making it limited in its diagnostic utility. Also, there are very few
BATs that have standardized coding and scoring of specific social behaviors, such as the SPRS. Most
BATs are used to collect anecdotal or qualitative clinical information pertinent to treatment. Although
this is clinically useful, it has low reliability as a standard diagnostic measure of social anxiety.
Assessment Summary
When childhood SP is in question, it is best practice to start with multiple informant ratings using
either broad-based anxiety measures that contain social anxiety subscales, or SP-specific rating scales.
If the child is rated in the clinically significant range on these screeners, then a diagnostic interview,
such as the Anxiety Disorders Interview Schedule for Children (ADIS-C) [76], would help in estab-
lishing a formal SP diagnosis. Once in the treatment phase, the clinician could periodically administer
child and parent rating scales, as well as coded BATs specific to the child’s social fears, in order to
monitor progress.
Treatment
The past decade has shown an increase in empirically supported treatments of childhood anxiety disorders,
including SP [77]. Cognitive-behavioral therapy (CBT) and selective serotonin reuptake inhibitors
(SSRI’s) have continuously garnered the most support [77–80].
Cognitive-Behavioral Treatments
The CBT literature has produced a solid evidence base for the treatment of childhood social anxiety.
Most of these studies use manualized treatment packages, composed of a combination of cognitive
and behavioral techniques [78, 81–83].
Many SP interventions, especially empirically supported manualized treatments, are provided in a
group format. Although it may seem counterintuitive to place socially anxious children in a social
treatment setting, this method has been shown to be highly effective. First, exposing an SP child to
a social environment, in and of itself, may help that child gradually reduce their anxiety in social
settings. Second, it allows the child to practice social skills in vivo, where he/she is likely to confront
similar emotions and cognitions as in a natural setting.
Social skills training (SST) is a group cognitive-behavioral intervention shown to be effective in
improving SP in children [81]. SST teaches children specific social skills (i.e., politeness, eye contact,
taking turns in conversation, complimenting others) by learning the steps to each skill didactically,
followed by role-playing these skills with the therapist and other members of the group and practicing
them during weekly homework assignments. The role-playing and practice integrated into SST allow
for continued skill refinement as well as constructive feedback on how to improve different aspects of
these skills. The rationale for SST in SP stems from research demonstrating that children with SP often
have inherent deficits in social skills that lead them to fear negative evaluation or rejection [65]. As a
result, SP children consistently avoid social situations and miss out on opportunities to develop and
hone social skills, causing any skill deficits to exacerbate. Thus, in SST, by focusing on development
and practice of social skills, children are more likely to enter feared social situations with a more
sophisticated ability to interact, thereby reducing the chances of being negatively evaluated by others.
Another effective cognitive-behavioral treatment for SP is Social Effectiveness Therapy for
Children (SET-C; [84–86]). SET-C is a multifaceted behavioral treatment that includes peer general-
ization exercises, individual in vivo exposure exercises, parent and child psycho-education about
anxiety, and components of SST. SET-C treatment lasts 12 weeks and consists of two sessions per
week—one individual and one group. Treatment focuses on developing social skills in a group
setting, such as greetings, starting and maintaining conversations, listening skills, joining groups, and
speaking on the telephone. Techniques used include didactic instruction of skills, modeling, behav-
ioral rehearsal, corrective feedback, and application of skills via homework assignments. SET-C also
includes peer generalization activities, where the SP children participate in social outings and are
encouraged to practice social skills learned in session with non-SP children. This component was
added due to the finding that social skills learned in the group therapy setting do not always generalize
to the natural environment. Lastly, individual sessions of in vivo exposure to feared social situations are
included. Examples of typically feared social situations include reading in front of a group, writing on
the blackboard, or acting out plays in front of an audience. The child completing the exposure exercise
is required to remain in the situation until their anxiety abates. In a randomized trial of 8–12-year-old
children with SP, SET-C was significantly more effective than a study skill comparison group. Results
indicated that 67 % of children treated with SET-C no longer met SP criteria at posttreatment compared
to only 5 % of the children in the study skills group [84].
Given that the efficacy of treating SP with SET-C had not yet been investigated in an applied clinical
setting, Baer et al. [85] replicated Beidel et al.’s [84] study using a modified version of SET-C,
consisting of 12 once-weekly, 1.5 h sessions with an experienced social worker and two supervised
psychiatric residents. In this community-based study, the investigators compared SET-C to a wait-list
control in a group of 12 adolescents ages 13–18 with SP. Results indicated that this community-based
application of SET-C was more effective than no treatment. At posttreatment, children in the wait-list
group received treatment. After analyzing their improvements, the investigators found that 91 % of SP
adolescents who received outpatient SET-C treatment were considered responders, with 36 % going
into full remission posttreatment.
Treatments such as SET-C, although conceptualized as CBT, use predominantly behavioral tech-
niques and do not focus on cognitive skills. However, cognitive-behavioral models of SP suggest that
a child’s social fears are fed by cognitions that are often overgeneralized, have catastrophic social
consequences, and magnify the potential for negative evaluation from others (i.e., “Others will think
I am stupid if I get a question wrong in class.” or “Kids are going to wind up laughing at me if I try to
talk to them.”).Thus, altering such cognitions can also be the vehicle used to treat social anxiety.
A child with extreme fear of speaking in class, due to the unrealistic belief that others will make fun
of him if he gets a question wrong, for example, can be coached to identify and challenge that belief,
for example, by gathering evidence that counters his automatic thoughts (i.e., “Cindy got a question
wrong in class yesterday, and nobody laughed at her.”).
Cognitive-behavioral group therapy for adolescents (CBGT-A) [78] is a 16-session multifaceted
intervention composed of behavioral and cognitive techniques. In this manualized treatment, sessions
one and two offer psycho-education to adolescents and parents about social anxiety and rationale for
treatment. Sessions 3–8 focus on skill building, including SST, social problem-solving, assertiveness
training, and cognitive restructuring. Sessions 9–15 offer graded in vivo exposure exercises of feared
social situations while applying skills learned in sessions 3–8. Children are also encouraged to com-
plete homework assignments throughout sessions 9–15 in the form of between-session exposure exer-
cises. Session 16 is composed of one final exposure, termination, and planning for posttreatment.
A pilot study of CBGT-A that treated five adolescents with SP [78] found significant treatment
gains for all five adolescents, and four out of five adolescents were still in full remission at 12-month
follow-up, with one in partial remission. Hayward et al. [87] conducted a larger investigation of
CBGT-A, by randomly assigning 35 adolescent females to receive either CBGT-A (n = 12) or a wait-list
control (n = 23). Although CBGT-A was significantly more effective than no treatment in improving
SP, improvements were not as robust as the previous pilot study [78]. At posttreatment, the CBGT-A
group showed significantly greater SP remission than the control group (45 % versus 4 %, respec-
tively); however, this significant difference did not hold up at 12-month follow-up. Although the
CBGT-A group maintained their remission 1 year after treatment, a large percentage of subjects in the
control group also showed remission, resulting in a nonsignificant difference between the two groups
in SP diagnosis 1 year after treatment. The authors also analyzed risk for major depression. Amongst
subjects with a history of major depression, those in the no-treatment group (64 % of subjects) were
more likely to relapse than the CBGT-A group (17 %), although this difference was nonsignificant
due to a small sample size. Thus, this study shows that CBGT-A is a moderately effective short-term
treatment for SP and may reduce the risk of relapse for comorbid major depression.
Standard CBT designed for child and adolescent SP typically involves only the child (either indi-
vidually or in a group), with minimal or no parental involvement; however, studies have shown that
providing adjunctive family therapy to CBT improves SP outcomes [81]. The rationale for providing
such treatment stems from findings that parental behaviors may exacerbate the child’s symptoms [55].
Parents’ enabling of social avoidance, by minimizing it as shyness or “just a phase,” can often
strengthen the child’s socially avoidant behaviors. Also, parents who express catastrophic fears toward
their child about the risks of social interactions, what others will think of him, or failure on a performance
can inadvertently increase their child’s anxiety. Thus, treatments have been developed to involve
parents so that these issues can be directly addressed.
Spence et al. [81] tested whether adding parental involvement to CBT would improve outcomes for
children with SP. Fifty children, ages 7–14, were randomly assigned into one of three groups to
receive 12 weeks of CBT alone, CBT plus parental involvement, or a no-treatment wait-list control.
The CBT alone treatment consisted of 12 group sessions of SST, relaxation training, social problem-
solving, cognitive challenging, positive self-talk, and gradual exposure to feared social stimuli. Parent
involvement group training sessions consisted of modeling, teaching, prompting of skills, ignoring
(not reinforcing) social avoidance, and encouraging participation of social activities and homework
assignments outside of sessions. At posttreatment, both CBT treatment groups showed significantly
higher remission rates than the control group (87 % of CBT + parent training, 58 % of CBT alone, and
7 % of control group). Moreover, at 12-month follow-up, both treatment groups maintained their treat-
ment gains, with 81 % of the parental involvement and 53 % of the CBT alone groups still not meeting
diagnostic criteria. Although the parental involvement group had a higher percentage of children
in remission both at posttreatment and 12-month follow-up, their improvement was not statistically
different from that of the CBT alone group.
Recent adaptations of cognitive-behavioral therapies for children and adolescents with social phobia
also show promise. These include brief intensive interventions and shifting the therapy setting to the
community or school. An intensive, brief group CBT intervention has been shown to be effective [88].
Twenty-three 8–11-year-old children were randomly assigned into either brief CBT or no treatment.
Three sessions, each consisting of 3 h, focusing on psycho-education, behavioral exposure, and
cognitive strategies, were shown to be more effective than no treatment at posttreatment. The brief
CBT group showed significant improvement in social phobia at posttreatment, when compared to the
nontreatment group. Results showed that 41.7 % of parents and 58.3 % of children no longer reported
social phobia at posttreatment. Moreover, children receiving this brief therapy maintained their gains
or showed even greater improvement at a three-week follow-up assessment, with 50 % of parents and
83.3 % of children no longer reporting significant social phobia on the ADIS-C.
Recently, SP-specific treatment programs have been tested or extended for application in the school
setting [83, 89–92]. Children with SP are rarely referred for treatment in the community [82]. This is in
part due to parents and teachers often thinking of SP as typical childhood shyness and something the child
will grow out of. Additionally, children with SP, who are typically withdrawn, tend to “fly under the radar”
in the classroom since they are more manageable than externalizing, disruptive children. Thus, the need
for proper assessment and treatment of childhood SP within the school setting is essential [83]. Skills for
Academic and Social Success (SASS) [91, 93] is a group treatment program adapted from the SET-C
and CBGT-A manuals to fit a school environment. SASS has consistently shown to improve adolescent
SP in the school setting, compared to no treatment [91, 94] as well as to an attention control group [93].
In addition to 12 treatment sessions, SASS includes three posttreatment booster sessions, weekend social
events, two parent meetings, and teacher consultation. The treatment is composed of five core compo-
nents: (1) psycho-education about anxiety; (2) development of “realistic thinking,” by relabeling overes-
timated negative outcomes and exaggerated consequences; (3) SST focusing on initiating and maintaining
conversations, establishing friendships, listening skills, and assertiveness training; (4) graded in vivo
exposures; and (5) relapse prevention, to prepare the adolescent for posttreatment challenges as well as
red flags for emerging symptoms.
Pharmacotherapy
Selective serotonin reuptake inhibitors (SSRIs) have demonstrated the most consistent pharmacological
efficacy across childhood anxiety disorders [80, 95] and for SP specifically [79, 86, 96]. For example,
after an eight-week open label trial [96] of sertraline, 36 % of children with social phobia were
considered responders, and 29% were considered partial responders. Significant response to treatment
was observed by week 6. Sertraline was generally well tolerated, showing only minimal adverse
effects. Research has also investigated SSRI treatment of child SP using double-blind placebo control
procedures [79]. A sixteen-week treatment with paroxetine resulted in a 77.6 % response rate, with
75 % of children deemed as “much improved” or “very much improved” in their global functioning,
compared to only 38 % of the placebo group.
In addition to open label and randomized placebo-controlled trials, researchers have also investigated
the efficacy of SSRI’s in treating SP when compared to CBT (SET-C) [86]. Results demonstrated that
both SET-C and fluoxetine were more effective than a placebo in improving SP, yielding 79 % and
36 % treatment response rates, respectively. However, SET-C was superior to fluoxetine in reducing
SP symptoms at posttreatment—53 % of SET-C children no longer met SP criteria, compared to only
21 % of the fluoxetine group. SET-C was also associated with improved social skills and self-ratings
of social competence. Moreover, whereas fluoxetine’s effect showed a plateau at week 8, SET-C
continued to yield improvements after 12 weeks of treatment. At 12-month follow-up, 61 % of the
fluoxetine group qualified as treatment responders, compared to 100 % of the SET-C group.
Treatment Summary
Although there are many unanswered questions about treatment efficacy, the past decade has shown an
increased in evidence-based treatments for childhood SP. Amongst psychotherapies, behavioral and
cognitive-behavioral therapies have garnered the most support. Several manualized treatments specific
to childhood SP have demonstrated effectiveness, including SET-C [84] and CBGT-A [78, 87]. CBT
treatments have also shown successful application in treating SP in the school setting [82, 91, 93],
with gains lasting upwards of 5 years [90]. Pharmacologically, SSRIs have repeatedly shown to be
effective in treating childhood SP [86, 97]. Yet, treatment with CBT improves social skills and rating of
social competence more so than SSRIs and shows continued improvements beyond treatment termina-
tion [87]. Although studies have not examined the combination of SSRI and CBT treatment in childhood
SP specifically, this combination treatment has shown to be the most effective intervention across
childhood anxiety disorders and may likely be the best option for treating childhood SP [80, 98].
Case Follow-Up
Upon presenting for treatment, Mike was diagnosed with social phobia and dysthymia, but he also
had the complication of school refusal behavior. Targets and goals were collaboratively developed by
the therapist, Mike, and his parents, with an emphasis on returning to school comfortably. A “fear and
avoidance” hierarchy was established that identified specific social situations that provoked increasing
levels of anxiety. Mike agreed to confront each of his fears over the course of treatment through expo-
sure exercises.
Mike initially began individual CBT as he refused to enter a group treatment. Mike was taught to
monitor his thoughts during anxiety-provoking social situations, particularly at school. He was able
to identify negative self-talk and participate in behavioral exposures which were primarily focused on
school reentry. The therapist introduced these exposure exercises by role-playing them with Mike
during therapy sessions and then having him complete them in vivo either in session or between ses-
sions for homework. Exposure tasks included calling classmates or meeting them socially after school
hours or on weekends, going to the school and sitting in the parking lot, and talking to his favorite
guidance counselor about school, first on the telephone and then in person. After only three individual
sessions, Mike was able to begin attending school for at least part of the day and was attending con-
sistently after his sixth session. While combination treatment of CBT and medication is often warranted
in severe cases of school refusal, it was not needed in this situation because Mike’s parents acted
quickly to seek CBT once the school refusal occurred. After his return to school, Mike continued in
treatment and agreed to join a group with other teenagers who presented with social phobia. The group
role-played realistic social challenges that are common for teenagers, such as being turned down for
a date or having people laugh during an oral report. After 12 sessions of group therapy, Mike was
reporting a significant decrease in social phobia symptoms.
Overall, given his positive response to treatment and his strong social support system, Mike’s prognosis
is favorable. However, given that he would soon be graduating from high school and entering college,
it is possible that his symptoms may relapse. Thus, Mike was given relapse prevention guidelines that
outlined how to manage his anxiety if he felt problematic anxiety returning.
Summary
Social phobia is one of the most common adolescent psychiatric disorders, with a typical onset in late
childhood. If left untreated, SP children may likely experience unremitting symptoms and impairment
throughout their adolescent development and have a high likelihood of developing comorbid disorders,
making it important to accurately assess and treat SP when symptoms emerge. Common treatments
for SP include CBT and SSRI antidepressant medications. Treatment studies consistently show that
these therapies provide significant reduction of social anxiety and improvement in functioning.
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Specific Phobias
Thomas H. Ollendick, Maria J.W. Cowart, and Ella L. Milliner
Abstract Specific phobias are highly prevalent, affecting 5–10 % of children and adolescents in
community samples and 15 % in mental health settings. Phobic youth experience significant interfer-
ence and distress in their day-to-day lives and are at an increased risk of academic and social difficulties
as well as adult psychopathology. Phobias have a complex etiology, developing from a multiplicity of
factors including genetics, learning history, parenting, and evolutionary preparedness. This chapter
reviews empirically supported assessment and treatment interventions for phobic youth. Strong
empirical support currently exists for cognitive and behavioral treatments. In particular, the chapter
focuses on the one-session treatment (OST) approach, which incorporates cognitive behavioral tech-
niques into an intensive (3-h) treatment package. OST is a cost-effective and rapid treatment for
phobic youth, with four randomized trials in four different countries now supporting its use. A case
report illustrating the implementation of this treatment is presented.
Keywords Specific phobia • Clinical phenomenology • Etiology • Assessment • Behavioral approach

task • Treatment • One-session treatment
Case Scenario
Andrew, an 8-year-old Caucasian boy, lived with his mother and 5-year-old sister. Andrew’s parents
had separated when he was 4 years of age. He and his sister had minimal contact with their father
who had moved to another state. Andrew was referred to our clinic for a phobia of being in the dark
alone that interfered with his own and their family’s lives.
Andrew’s mother stated that he slept in her room every night. She permitted co-sleeping to ensure
that Andrew got a good night’s sleep before attending school. On weekends, he slept in a room that he
shared with his sister. However, he would insist on having the television on and a night and hall light
illuminated. If disturbed during the night, Andrew called out to his mother until she awoke and
T.H. Ollendick (*) • M.J.W. Cowart

Virginia Tech, Child Study Center, Blacksburg, VA 24060, USA
e-mail: tho@vt.edu
E.L. Milliner
Griffith University, Room 3.15, Business 1 Building (G01), Parklands Drive, Southport,
Gold Coast, QLD 4222, Australia
114 T.H. Ollendick et al.
responded. Andrew also avoided entering dark rooms in the family house. He refused to go into the
basement and, if asked to bring his mother something from upstairs at night, he would become highly
distressed and ask his sister to go for him. When arriving home in the car at night when it was dark,
Andrew waited for his mother to enter the house and turn on the lights and then he would sprint
inside. During a recent power outage, Andrew was crying, shaking, and clinging to his mother. Andrew
has never been able to sleep over at friends’ houses because of his fear. He was able to go trick-or-
treating and to the movie theater in the dark; however, during these times he stayed close to his
mother. Andrew’s mother stated that she had not previously sought assistance for Andrew’s fear
because she initially believed Andrew would “grow out of it” and that his fear was “just a phase.”
However, as time progressed and Andrew’s fear worsened, she decided they needed assistance.
Fear is a normal part of child development [1, 2]. The content of childhood fears follows a predictable
course that is associated with increasing cognitive development, progressing from concrete fears
(e.g., fears of strangers and animals) in infancy and toddlerhood to increasingly abstract fears in childhood
(e.g., ghosts and the supernatural) and into adolescence (e.g., social fears, agoraphobia; see [3–5]).
Specific fears become less common over the course of childhood, peaking in early childhood between
the ages of 7–9 years and declining in children 10 years and older [4]. As a result of this trend, parents
and health professionals often attribute children’s fears to being “just a phase” and expect them to
diminish over time [5]. However, in a subset of children, these transient or “normal fears” become
more frequent, intense, and durable and eventually evolve into a phobia [2].
The Diagnostic and Statistical Manual of Mental disorders [6] delineates the following criteria for
a child’s fear to be classified as a specific phobia: the fear must be intense, enduring, and cued by the
presence or anticipation of a specific object or situation (Criterion A); exposure to the phobic stimulus
must trigger an immediate anxiety response or panic attack (Criterion B); the person must realize their
fear is excessive and unreasonable (however this criteria is not necessary in children) (Criterion C);
the child must attempt to avoid the phobic stimulus or, if such is not possible, to endure it with distress
(Criterion D); avoidance of the phobic stimulus must interfere significantly with the child’s academic,
social, and family functioning (Criterion E); in youth the fear must be present for at least 6 months
(Criterion F); and the fear cannot be better accounted for by another mental disorder (Criterion G) [6].
The DSM-IV-TR criteria take into consideration the tenets of developmental psychopathology [5, 7].
A child must experience their fear for a long enough time period (6 months) to suggest that it is not
developmentally appropriate or “just a phase.” Moreover, unlike adults, children are not required to
recognize that their fear is excessive or unreasonable.
According to Lang’s tripartite model [8–10], fear and the phobic response are comprised of a neural
network of three components: cognition, physiology, and behavior. When exposed to a fearful object
or situation, a child may think catastrophic thoughts (cognitive component) and experience an activa-
tion of their autonomic nervous system, including an increased heart and/or breathing rate, sweating
and shaking (physiological component), and engagement in avoidance behavior such as running
away, having a tantrum, crying, freezing up, or clinging to their caregiver (behavioral component)
[11]. These components are considered concordant if they covary together and discordant if they vary
independently of one another. Concordance is thought to be associated with greater levels of fear [12].
In a recent study, Ollendick, Allen, Benoit, and Cowart [13] investigated concordance and discor-
dance in a group of 73 phobic youth who completed phobia-specific behavioral tasks. The results
showed that overall when confronted with their feared object/situation, most phobic youth tended to
Specific Phobias 115
show concordant responding; however, significant intersubject variability was observed. Specifically,
a minority of youth were characterized as responding predominantly along one dimension and not the
others. For example, primarily physiological responders exhibited increased physiological arousal
(e.g., increased heart and/or breathing rate, sweating and shaking) in the absence of negative cognitions
or behavioral avoidance. The significance of concordance versus discordance is not fully understood
at this time.
Prevalence and Course
Specific phobia is one of the most common psychological disorders, affecting approximately 5–10 %
of children and adolescents in community samples and 15 % in mental health settings [14–16].
Specific phobias are classified into five major types: animal (e.g., dogs, insects, snakes), natural envi-
ronment (e.g., thunderstorms, heights, darkness), situational (e.g., elevators, flying), blood-injection-
injury (e.g., seeing blood, injections), and others (e.g., loud noises, costume characters) [6]. Among
the phobia subtypes, animal and natural environment are the most frequently observed in children
[17–19]. The average age of onset for specific phobias is 9–10 years of age [3, 20]. However, similar
to the pattern observed with normative fears, the onset of specific phobia subtypes follows a develop-
mental progression with animal phobias emerging at about 7 years of age, followed by blood-injection-
injury phobias at 9 years, situational fears at approximately 13 years of age, and claustrophobia at
20 years of age [21]. Phobic youth frequently experience increased risk of academic difficulty [22–24]
as well as social and personal distress [25–27]. Furthermore, if left untreated, phobias can persist into
adolescence and adulthood [2] and contribute to the development of other psychiatric disorders
including adult anxiety, depression, and substance use [28].
Comorbidity
Comorbidity (i.e., co-occurrence of other disorders) is the rule rather than the exception in children
and adolescents with specific phobia. Community and clinical studies suggest that 25–72 % of phobic
youth meet criteria for at least one comorbid psychiatric diagnosis [17, 19, 25, 29, 30]. Specific
phobias are most commonly comorbid with other anxiety disorders including generalized anxiety
disorder (GAD), social anxiety disorder, separation anxiety disorder, and obsessive-compulsive disorder.
Prevalence rates suggest that 50 % of phobic youth also meet criteria for more than one phobia [29].
Comorbidity between specific phobia and mood or externalizing disorders is also observed [17].
Current research suggests that the presence of comorbidity does not negatively affect phobic treat-
ment outcome. Moreover, Ollendick and colleagues [30] found that successful treatment of specific
phobias resulted in reductions in the clinical severity of other comorbid anxiety disorders.
Etiology
Childhood phobias have a complex and multifactorial etiology [7] Several pathways, including
genetic influences, learning experiences, as well as parenting and evolutionary preparedness are
thought to be involved in the development of a specific phobia [11].
Genetics
Family and twin studies indicate that specific phobia is a familial disorder [31]. Research suggests that
phobias “breed true” in that the offspring of phobic individuals are more likely to develop the same
type of phobia as their parent. In a recent literature review, LeBeau and colleagues [32] found evi-
dence of familial aggregation, with children of phobic individuals at increased risk only for the phobia
exhibited by their parent. Conversely, some studies suggest a common genetic vulnerability for
animal, natural environment, and situational types of phobia and a separate and distinct genetic risk
for blood-injection-injury phobia [33]. Additional research indicates that there is a general genetic
vulnerability that makes individuals susceptible to a range of anxiety disorders and that other factors
determine the specific anxiety presentation [34]. Hence, genetics appear to play an important role in the
etiology of phobias. However, at this time, there is insufficient information to determine its exact role.
Learning
Rachman [35, 36] proposed that phobias are acquired through three learning pathways: direct/classical
conditioning, vicarious conditioning (modeling), and the transmission of negative information.
Phobia acquisition, as a result of direct conditioning, must involve a direct negative experience with
the phobic object/situation. For example, a child that is bitten by a dog and then develops a dog
phobia is said to have acquired their phobia through direct conditioning. Second, children may acquire
their phobia vicariously through modeling and the observation of others’ anxious behavior towards
the phobic object/situation. An example of this type of learning would include a child who develops
a phobia of spiders after observing his/her mother or father behave in a fearful manner around spiders.
The third pathway proposed by Rachman is that a child may acquire a phobia through hearing nega-
tive information about the phobic object. For example, a child may develop a phobia of storms after
watching a news story about someone being struck by lightning or a town affected by a tornado or
hurricane. Multiple learning pathways may be simultaneously involved in the acquisition of a child’s
phobia [37, 38].
Parenting
Parenting factors are also thought to play a role in the development of child phobias. Research
suggests that the parents of anxious children have a more “intrusive” and “overprotective” parenting
style [39–43]. Such parents are more likely to intervene and attempt to protect their child from nega-
tive emotional experiences [44]. In interaction studies where parent and child dyads are observed in
ambiguous or stressful situations, parents of anxious children are more likely to intrude on their children
in an attempt to protect them from potential upset or harm [39, 41]. In relation to phobias, parents may
accommodate and reinforce their child’s avoidance of the phobic object/situation in order to prevent
them from having a negative experience [11]. For example, a parent may allow (or even invite) their
child to sleep in their bed if the child fears the dark or may avoid going to football games because their
child is afraid of costumed characters and becomes upset when they see team mascots. These patterns
prevent children from gaining positive information about their phobic object, which could challenge
their fear-related beliefs [11]. Hence, in these instances, the child does not have the opportunity to
learn that the fearful events they anticipate in fact do not occur.
Nonassociative
The aforementioned etiological pathways may not account for all causes of specific phobia. According
to the nonassociative model of fear acquisition, some fears (e.g., waters, heights, snakes) may be
biologically prepared through evolution [45–47]. That is, at some point in time, these fears were evo-
lutionarily adaptive and necessary for survival and then were passed on to us from our ancestors and
therefore may not require critical learning experiences. This may account for fears and phobias that
parents report have “always” been present in their child. In particular, studies of water-phobic children
have predominantly found a nonassociative onset, with few children experiencing a direct or indirect
conditioning event [45, 48]. In comparison to other studies investigating fear acquisition in animal-
phobic children [37, 49, 50], it appears that water-phobic children do not require a negative learning
experience. However, further research is still necessary to determine whether water phobias are a
“special case” in terms of their etiological pathway [37].
Assessment
Given the complex clinical presentation (e.g., etiology, phenomenology, and comorbidity) of specific
phobia, a thorough, evidence-based assessment is critical to the effective provision of treatment.
A comprehensive assessment should ideally be multi-method (e.g., clinical interview, questionnaires,
observation) and multi-informant (e.g., child, parent, teacher) to gain an accurate diagnostic picture
of the child across contexts and settings [51–53]. To develop a complete understanding of the child’s
phobia, it is also necessary to investigate all aspects of the phobic response (cognition, psychophysiol-
ogy, and behavior). As discussed previously, specific phobias are frequently comorbid. Accordingly,
a broad assessment of psychopathology is required to identify comorbid conditions and assist in
differential diagnosis (e.g., separation anxiety versus phobia of the dark). It is also important for clini-
cians to consider the developmental trajectory of fears and consider what is normative for the child’s
developmental level [11]. A variety of tools are recommended for the assessment of phobias, includ-
ing diagnostic interviews, questionnaires, and observational methods. A more thorough description of
broad based measures of anxiety is presented in Chap. 12. This chapter will focus on phobic specific
measures for children.
The Fear Survey Schedule for Children-Revised (FSSC-R; [54]) is considered the gold standard
specific phobia questionnaire. It assesses overall fearfulness and yields information about a range of
specific phobias and social phobia. The measure requires youth to rate their level of fear of 80 specific
objects and situations. Higher scores indicate greater overall fearfulness and suggest the presence of
a specific phobia. The FSSC-R consists of five factors including fear of danger and death, fear of
failure and criticism, fear of the unknown, fear of small animals, and medical fears. Examination of
specific phobia items can be helpful in identifying the presence and severity of a phobia. The FSSC-R
has well-established reliability and validity and provides norms for boys and girls of various ages and
nationalities. Additionally, it has been translated into several languages [55].
Questionnaires designed for the assessment of individual types of phobia are also available, such
as the Spider Phobia Questionnaire for Children. This questionnaire consists of 29 items and provides
the clinician with an overall spider fear score (SPQ-C; [56]).
Behavioral approach tests (BATs) are an integral part of any phobia assessment as they allow the
clinician to observe the child’s phobic behaviors directly. The BAT is a controlled and standardized
test in which individuals are asked to approach a phobic object or stimuli so that their avoidance
behavior can be objectively observed [2]. For example, a child who is afraid of costumed characters
may be brought to a door and informed that inside is a costumed character (e.g., a clown) sitting on a
chair. The child is then instructed to enter the room, shake hands with the costumed character, and
interact with it for a few minutes. Additionally, the child is told that he/she only needs to complete as
much of the task as he/she feels comfortable with and can stop at any time. The degree to which the
child complies or avoids the therapist’s instructions provides an objective measurement of phobic
avoidance [2]. Periodically throughout the BAT, the clinician may ask the child to rate his/her level of
fear on a 0 (not at all) to 8 (very high) scale. Physiological data, such as heart rate and heart rate vari-
ability, may also be collected. This enables the clinician to assess all three components of the child’s
phobic response (cognition, physiology, and behavior) [11]. The BAT allows the clinician to observe
the child’s avoidance behavior directly in the presence of the phobic object or situation and confirms
information obtained from diagnostic interviews and questionnaires.
While behavioral approach tasks are sometimes challenging to arrange (e.g., retrieving, storing,
and caring for stimuli or scheduling offsite visits), especially for private practitioners with limited
resources, assistance, and space, the incorporation of BATs into the assessment process is strongly
recommended [51]. The BAT is an essential tool in treatment planning. It provides a foundation on
which to build a graduated exposure hierarchy for use in treatment [11]. The child’s behavior during
the BAT gives an indication of a possible starting point for treatment and the child’s ability to interact
with the phobic object or stimuli. Additionally, the BAT may provide insight into the child’s motivation
to face their fear and their willingness to engage in therapy [11]. A standardized BAT format can be
developed and adjusted for a range of possible phobia types. BAT performance is measured by the
percentage of steps completed by the child [e.g., open the door (step 1), stays arm’s length from
costumed character for 10 s with no attempt to shake hands (step 4)], and his/her fear ratings [2].
To investigate the cognitive component of the child’s phobic response further, the clinician may
choose to interview the child to elicit their catastrophic beliefs about the phobic object or situation
(e.g., “The needle will touch my bone,” or “the dog will bite me,” or “a bat will fly out of the dark and
attack me”). To gain a more objective measure of the child’s phobic beliefs, the child can be asked to
rate on a 9-point scale (0–8) how likely the belief is to occur (probability), how bad it would be if it
actually occurred (danger), and how sure the they are that they could cope with the event were it to
occur (self-efficacy). This can be carried out for the child’s most severe phobic beliefs and be reevaluated
during and following the completion of treatment.
Andrew and his mother were interviewed using the Anxiety Disorders Interview Schedule for
DSM-IV Child/Parent version (ADIS-IV-C/P; [57]) during their initial appointment at our clinic.
Based on Andrew’s report and that of his mother during the interview, Andrew was diagnosed with a
specific phobia of the dark (Clinician Severity Rating = 7) and GAD (Clinician Severity Rating = 4).
Following the interviews, a BAT was administered during which Andrew was asked to enter a dark
room by himself and sit in a chair with the door closed for 5 min. Andrew refused to enter the room
and reported his subjective anxiety to be at a 7 (on a scale ranging from 0 to 8).
Treatment
Behavioral therapy and cognitive behavioral therapy (CBT) have received strong empirical support in
the treatment of childhood phobias [5, 52]. CBT uses a combination of behavioral techniques to
address behavioral avoidance and physiology associated with anxious behaviors and cognitive techniques
to address catastrophic cognitions, attentional biases, and cognitive distortions [58–61]. For specific
phobias, CBT involves graduated exposure, reinforcement, participant modeling, psychoeducation
about the feared object or situation, behavioral skills to assist with interacting with the feared object,
and cognitive techniques such as skills to identify and challenge cognitive biases and distortions.
Exposure-based therapies have been found to be particularly efficacious [62]. Specifically, techniques
such as systematic desensitization, reinforced practice or contingency management, and modeling

and participant modeling have all been shown to be effective with these youth [52]. There is limited
evidence to support the use of psychopharmacological intervention in phobic youth [63]. Behavioral
techniques will be discussed below followed by a description of a one-session CBT session that
utilizes these methods. Additionally, psychopharmacological interventions will be explored.
Behavioral Techniques
Systematic Desensitization
One of the earliest and most influential treatments for specific phobia in children is systematic desen-
sitization [51, 64, 65], a form of “counterconditioning,” which is the opposite of classical conditioning.
This approach, developed by Wolpe [66], is purported to work through the process of reciprocal
inhibition, which is based on the notion that an individual cannot experience two incompatible emo-
tions (e.g., fear and relaxation) simultaneously. Systematic desensitization involves exposing the
patient to a feared object or situation, while an emotion other than fear (e.g., relaxation) is experienced
[51]. Treatment typically consists of training in progressive muscle relaxation and the development of
a graduated fear hierarchy. The latter involves creating a list of different situations that trigger fear,
followed by rating each fear on a scale of 0–8. Systematic desensitization involves having the child
utilize progressive muscle relaxation before they are exposed to low-level exposure tasks. Hence, the
child experiences minimal levels of anxiety in the presence of the phobic object or situation. Stronger
versions of the phobic stimulus are gradually introduced with dissipation of anxiety at each stage
through relaxation techniques. In theory, the association between the phobic object and the child’s
fear response should be weakened when the child does not feel excessively afraid during exposure
tasks [60, 64]. Due to the physical and cognitive demands of systematic desensitization, it has been
used less frequently with young children [11, 52]. Systematic desensitization (imaginal and in vivo)
has been found to be superior to no treatment [67–72] for childhood fears and phobia. Additionally,
imaginal systematic desensitization has been found to be superior to relaxation training [68], however
inferior to modeling [70].
The theory and procedures underlying systematic desensitization have been increasingly scruti-
nized in recent years [5]. Research into extinction of fear associations has resulted in an understanding
of exposure as creating a new positive learning experience as opposed to Wolpe’s [66] hypothesis of
“counterconditioning” or unlearning of the fear response [51, 73]. Additionally, systematic desensiti-
zation has not been shown to consistently affect a child’s physiological responses to fear. This finding
opposes the notion that the clinician is conditioning a different, competing physiological response
(e.g., relaxation) [60]. Enthusiasm for systematic desensitization research has therefore waned over
the past several decades, and the field has moved towards in vivo exposure with fewer distractions
(e.g., relaxation and diaphragmatic breathing) [60]. Based on early investigations, systematic desen-
sitization has enough research support to warrant probably efficacious empirical status for alleviating
fears; however, large-scale randomized controlled trials with carefully diagnosed youth have not been
carried out. Hence, this approach is still considered experimental for the treatment of childhood
phobias [11, 51].
Reinforced Practice
Reinforced practice (also referred to as contingency management) is another behavioral approach used
to treat childhood-specific phobia. Reinforced practice has received considerable research support
and as such is considered an evidence-based treatment for childhood fears [60]. Based on operant
conditioning principles, reinforced practice involves reinforcing successive steps towards the feared
object or situation, thus stopping avoidance behavior [60, 65]. Similar to systematic desensitization,
reinforced practice requires the development of a fear hierarchy with the child. However, reinforced
practice does not include the use of a competing response, e.g., relaxation [11]. The goal of reinforced
practice is to alter avoidance behavior through the manipulation of the consequences of the behavior.
The clinician works with the child to develop a list of desirable reinforcers (e.g., social praise, stickers,
and food items). Following this, the clinician gives the child the discussed reinforcers contingent upon
the completion of increasingly difficult steps on the fear hierarchy. Using this technique, behavior can
be shaped and changed over time, with reinforcers decreased and eventually faded out [60]. Reinforced
practice has been found to be more effective than no treatment [74, 75], verbal coping [76], and mod-
eling [77] and equivalent to CBT [18] for the treatment of childhood fears and phobia.
Reinforced practice and systematic desensitization have often been confused in the literature, and
their distinction is of theoretical and practical importance. The critical issue is when a competing
response (as in systematic desensitization) or reinforcer (as in reinforced practice) is delivered. In
systematic desensitization, a competing response is initiated before the fear occurs in an attempt to
prevent the fear response from occurring [5]. Conversely, in reinforced practice, the reinforcer is given
as soon as possible after the approach behavior and coincident fear response occurs. Thus, the goal of
reinforced practice is for the child to experience a manageable amount of fear and for extinction of the
avoidance behavior to occur by strengthening positive associations with the phobic stimulus through
reinforcement of approach behaviors [51].
Modeling and Participant Modeling
Modeling is based on social learning theory [78] and involves the therapist (e.g., model) demonstrating
how to approach and appropriately interact with the phobic object or situation [60]. Observing another
person interact successfully with the feared stimulus is thought to weaken the association between the
object and experience of fear in the observer, as new learning competes with his/her fear [5]. Participant
modeling expands upon modeling by encouraging the observer to interact with the model and the
feared object or situation [5]. Phobic children are encouraged to interact with the therapist and phobic
stimuli using a number of techniques, ranging from simple verbal instructions to physical contact such
as hand-over-hand assistance [51, 64]. For example, when treating a dog-phobic child, participant
modeling may progress as follows: (1) the therapist models patting the dog, (2) the child is instructed
to place their hand on the therapist’s shoulder, and (3) the child is gradually encouraged to move their
hand down the therapist’s arm and finally, (4) the therapist uses hand-over-hand assistance to assist the
child to pat the dog. The goal of participant modeling is to gradually phase out the therapist’s instruction
and physical contact and for the child to be able to engage independently in steps from his/her fear
hierarchy.
Participant modeling is a well-established treatment for childhood fears [60]. It has been found
to be superior to no treatment [79, 80], live [81], and filmed modeling [82, 83] and also to systematic
desensitization [82]. The benefits of participant modeling include skill building (e.g., learning how to
safely approach and pet a dog) and breaking down exposure tasks into smaller, more manageable,
steps (e.g., patting a dog versus watching someone pat a dog followed by moving their hand slowly
down the therapist’s arm while they pat the dog). Often participant modeling has been misconstrued
as only usable with animal phobias [84, 85]. However, in actuality, participant modeling can be
used with multiple phobia types, such as natural environment, blood-injury-injection, and costumed
characters. For example, the therapist may model having their blood pressure taken (e.g., blood-
injury-injection phobia), followed by the child having their blood pressure taken with the therapist
placing their hand under the blood pressure cuff.
One-Session Treatment
More recently, cognitive behavioral procedures have been incorporated into an intensive one-session
treatment (OST) package in the treatment of specific phobia in children and adults [86]. OST involves
a single, 3-h session of massed exposure that includes aspects of psychoeducation, skills training,
cognitive restructuring, graduated in vivo exposure, reinforced practice, and participant modeling.
The single session is preceded by a 45-min functional assessment session, during which the thera-
pist meets with the child and his/her parent(s) to elicit the child’s phobic cognitions (e.g., phobic
beliefs assessment, refer above), develop a graduated exposure hierarchy, and give information about
the OST session [11, 84]. The therapist explains to the family the rationale for treatment. The child is
encouraged to think of himself or herself as a “scientist” or “detective” who will be testing out their
cognitions through a series of behavioral “experiments” (e.g., exposure tasks; [11, 51, 84]). Children are
advised that treatment will proceed at their pace and that nothing will be done without their permission.
They are also informed that the goal of the session is not to shock or surprise them, rather for the clini-
cian and child to work as a team to face the child’s fear gradually. The clinician explains that the child
will need to experience some fear during the session to overcome his/her fear, however this will be a
manageable amount of fear and that if he/she remains in the situation, without avoiding, his/her fear
will subside or considerably reduce [84]. In addition to providing important details about the child’s
fear, the functional assessment session gives the therapist an opportunity to build rapport with the
child and increase his/her motivation for treatment. It is ideally carried out 1 week prior to the OST to
allow time to use the information gathered to prepare for the exposure session.
OST sessions may vary considerably from child to child, even when the same type of phobia is
treated [51]. This is because the therapist works at the child’s pace and adjusts his/her approach based
on the child’s response (e.g., fear levels and behavior) to various exposure activities. Consequently,
there is no standard format for structuring an OST session [64]. Ideally, at least three phobic objects/
situations (approximately one per hour) are introduced during the session. In order to engage the
child and increase his/her motivation, exposure activities should be as fun and engaging as possible.
For example, when treating a child with a blood-injury-injection phobia, the therapist and child could
pretend to be doctors, dressing up in scrubs and treating fake wounds on each other. Throughout the
session, the therapist should frequently praise the child for engaging in exposure tasks and reinforce
approach behaviors to make the experience more positive for the child [11].
Throughout treatment, behavioral experiments are completed. While there is some variation,
behavioral experiments typically proceed as follows: (1) the therapist and/or child suggests and dis-
cusses a possible exposure task, (2) the therapist models the proposed experiment, (3) the child
attempts the modeled task (with the assistance of the therapist if necessary), and (4) success or failure
is discussed [51, 84]. After agreeing about a behavioral experiment, the cognitions identified during
the functional assessment are used to prompt the child as to what they believe will happen during the
experiment (e.g., “Do you think the dog will bite you if you pat him on the head?”). Following the
experiment, the child and the clinician review what actually happened and discuss whether the child’s
cognition came true [51]. While carrying out the behavioral experiments, the therapist provides the
child with psychoeducation about the phobic object, highlighting positive information (e.g., snakes
help control mice and rat populations) and training in how to successfully interact with the phobic
object (e.g., how to read a dog’s body language to determine if it is friendly; [11]). To assist in gener-
alization, exposure tasks should be repeated and, if possible, across multiple contexts (e.g., interact
with a dog in a therapy room, a backyard, and an open unfenced park). At the conclusion of the session,
the child and his/her family should be reminded to schedule regular practice exposure tasks to further
progress and prevent relapse.
OST is considered an evidence-based treatment for childhood-specific phobia [51]. The efficacy of
OST has been supported by two large randomized controlled trials (RCTs, [87, 88]) and two smaller
clinical trials [89, 90]. In the first of the large randomized controlled trials, Öst and colleagues [88]
in Sweden compared OST alone, with OST with a parent present and a waitlist-control condition.
In the parent’s present condition, the parent acted as source of support for the child and if necessary
was called upon by the therapist during the session to be either a model for the child or to comfort
them in times of high anxiety. Sixty children and adolescents (7–17 years) with a diagnosis of a
specific phobia participated in the study. Both OST conditions were found to be superior to the waitlist-
control condition on the primary outcome measures of subjective distress, behavioral avoidance, and
independent assessor ratings of the severity of phobias at posttreatment. Treatment gains in both OST
groups were maintained at 1-year follow-up. In a subsequent large-scale randomized control trial,
Ollendick et al. [87] evaluated the efficacy of OST (alone without parent present) to an education sup-
port treatment and a waitlist-control condition. One hundred and ninety-six children and adolescents
(7–16 years) with various specific phobias participated in the study. Participants were recruited from
Sweden and the USA. OST and the education support treatment were found to be superior to the
waitlist-control condition. Moreover, OST was found to be superior to the education support treat-
ment on clinician ratings of phobic severity, percentage of participants diagnosis-free (55 % OST
versus 23 % EST) at posttreatment, child ratings of anxiety during the behavioral avoidance test, and
treatment satisfaction as reported by youth and their parents. Treatment gains were maintained at
6 months follow-up.
OST has been shown to be effective for approximately 50–60 % of children [87]; hence a number
of children continue to experience clinically significant levels of fear following treatment. Given that
research suggests that parents may inadvertently reinforce and maintain their children’s fears [39],
treatment that includes a parent component may lead to enhanced outcomes [91, 92]. Ollendick and
colleagues are currently evaluating a parent-augmented OST, in which standard OST is supplemented
with parent training [11]. Parents are given the opportunity to observe their child’s treatment to learn
strategies to engage their child in exposure activities at home. Moreover, parents are invited to join the
last half hour of the OST session and are assisted in leading an exposure activity with their child.
Hence, control over exposure activities is gradually transferred from therapist to parent. Additionally,
parents receive psychoeducation regarding fear and anxiety and are trained in the use of a contingency
management program. Parents are then encouraged to implement a program at home that rewards
their child for engaging in exposure tasks. The approach appears promising.
Pharmacological Treatments
There is limited support for the use of psychopharmalogical approaches as stand-alone treatments
for specific phobia. Currently, in the child and adult literature, only a few case reports and small con-
trolled trials exist [93–95]. A 9-week open label trial of fluoxetine (mean dose: 24 mg children and
80 mg adolescents) showed that four of the six participants with specific phobia responded to treat-
ment [95]. Many phobic children and adolescents have comorbid anxiety disorders. Pharmacological
and cognitive behavioral treatments are therefore frequently used to treat these comorbid anxiety
disorders [63, 96]. Selective serotonin reuptake inhibitors (SSRIs) have previously been proven to be
effective in pediatric generalized anxiety disorder, social phobia, separation anxiety disorder, and
obsessive-compulsive disorder [63, 96–98]. Based on this literature, SSRIs may be beneficial in the
treatment refractory phobic youth [5].
There is a growing body of research examining the augmentation of exposure therapy for specific
phobia with the cognitive enhancing drug d-cycloserine (DCS). DCS is hypothesized to have an effect
on the formation and consolidation of fear and learning extinction. DCS may strengthen extinction
memories, thus making them easier to recall when exposed to the phobic object or situation in future
(see [99] for review; [11]). DCS has been proven to be effective with adults with specific phobia of
heights [100], but not effective in the treatment of subclinical spider phobia in adults [101]. Studies
evaluating the effectiveness of OST treatment augmented with DCS in pediatric samples are currently
underway. DCS augmentation of exposure therapy is a promising development in the treatment of
child- and adolescent-specific phobia. However, at this time it is considered experimental and future
research is needed to determine whether these approaches are as efficacious with children as they have
been with adults.
Case Follow-Up
Functional assessments were conducted with Andrew and his mother (separately) to establish (1) the
antecedents and consequences of Andrew’s avoidant behavior, (2) his faulty cognitions about being in
the dark alone, and (3) an avoidance hierarchy of his fears. Andrew reported that he was scared of the
dark because of a “scary movie” he had seen. He was afraid the characters from the movie would
appear when he was in the dark. He reported that the sounds he heard at night and the shadows he
saw frightened him because he believed it could be one of the movie characters walking around or
hiding in the house. He stated that the worst thing that could happen to him when he was in the dark
would be someone breaking into the house. While Andrew met with the child therapist, his mother
simultaneously met with the parent therapist. In addition to completing a functional assessment of
Andrew’s phobia, the parent therapist provided Andrew’s mother with psychoeducation about the
cycle of fear/anxiety and about the factors that maintain these symptoms in children. At the conclusion
of the functional assessments, Andrew and his mother were brought together and the treatment ratio-
nale for OST was explained. The treatment was scheduled for 1 week later.
The first hour of treatment was carried out at our clinic. The family’s appointment was scheduled
at nighttime to allow for maximum opportunity for exposure to the dark and elicitation of Andrew’s
fear. Initially, the child therapist provided Andrew with psychoeducation about the dark (e.g., why it
becomes dark at night, why we hear strange noises at night, how our vision changes in the dark, and
education about nocturnal animals). Following this, the lights in the room were turned off and Andrew
and the therapist played games with glow-in-the-dark toys, such as glow sticks. For example, Andrew
and the therapist took turns hiding glow sticks for the other to find. The therapist gradually increased
the number of rooms they could hide glow sticks in as well as reducing the number of glow sticks used
in the game so that there was less light. At the end of the first hour, Andrew was able to wait alone in
the “base room” by himself in the dark with the door closed for up to 5 min. Throughout the first and
subsequent 2 h of treatment, the child therapist provided Andrew with profuse praise for facing and
coping with his fears. A playful, supportive, and trusting relationship was developed.
The second and third hours of treatment were conducted outside of the clinic in an old two-story
house that had been converted into offices in order to expose Andrew to a more realistic “in vivo”
home situation in the hope that this would result in greater generalization of his treatment gains.
Andrew and the therapist first sat quietly in one of the dark rooms focusing on the sights and sounds
they could see and hear. Following this, Andrew stayed in the room alone for 2 min. When the therapist
returned, Andrew appeared upset and reported that he had seen a shadow that looked like someone
walking by. The therapist helped Andrew challenge and disconfirm his catastrophic cognition by
investigating and discovering that the trees moving outside had made the shadow. This exposure task
was then repeated three more times to ensure that Andrew sufficiently habituated to his anxiety.
Following this, Andrew and the therapist played hide-and-seek across both levels of the two-story
house. Andrew’s mother and the parent therapist observed the session from an observation room.
Throughout the course of the 3 h, the parent therapist pointed out the child therapist’s use of instruction,
modeling, reinforcement, and cognitive challenges to help Andrew to face his fear. Andrew’s mother
was educated regarding contingency management strategies and generating an exposure hierarchy
to practice with Andrew following the completion of the treatment.
At the commencement of the third hour, the therapist had Andrew lie down on a couch, pretend
he was in bed, and focus on his scary thoughts while she left the room. Afterwards he reported that
he had thought about the “scary” movie characters. The therapist pointed out that, although he
had scary thoughts, nothing bad had happened and that he was able to cope. This task was then
repeated three times. During the last half hour of the session, Andrew’s mother joined them, and she
and Andrew hid glow sticks in the woods outside their house and took turns finding them. This pro-
vided the mother an opportunity to practice exposure activities with Andrew and to foster a transfer
of control from the child therapist to her. Andrew and his mother were reminded that this was only the
beginning of Andrew’s treatment, and for the treatment to work fully it would be important for them to
continue exposure activities outside of therapy for at least the next month to solidify the gains that had
been made.
Upon post-testing 1 week later, Andrew’s fear had reduced considerably from his pretreatment
levels. However, his phobia of the dark was still clinically significant, as evidenced by his Clinician
Severity Rating of 5 on the ADIS-IV C/P and his inability to sit in a dark room at the clinic for a full
5 min alone (a BAT identical to that used at pretreatment). Andrew and his mother were encouraged
to continue practicing exposure tasks outside of treatment for the next month. One month later, Andrew
was reevaluated. His mother reported that they had been practicing on a regular basis. She stated that
Andrew could now go outside at nighttime to say goodnight to his rabbits (who were kept outside),
bring things in from the car at night, and go into the basement and play with glow sticks and shadow
puppets in the dark. Additionally, Andrew had transitioned from sleeping in his mother’s bed to lying
in his own bed for 15 min before going to his mother’s room, and then sleeping in his own room with
his sister present and the nightlights on, and finally to sleeping in his room alone with minimal night-
lights on. Andrew’s ADIS-IV C/P rating for a specific phobia of the dark was a 3 (subclinical level)
and for GAD, a 2. During the BAT at follow-up, Andrew was able to stay alone in the dark room for
a full 5 min. At the 6 months follow-up, Andrew continued to have little or no fear about being in the
dark alone. He was able to sleep alone in his room in the dark without any nightlights. He was also
able to attend sleepovers with friends. Furthermore, his mother reported that she felt more confident
in managing Andrew’s anxious behavior.
Summary
Transient fears are a normative part of childhood development. However, for some children fears
persist and increase in frequency, intensity, and duration, eventually becoming a phobia [2]. Specific
phobia is one of the most common psychological disorders in children and adolescents. Phobias often
cause significant interference and distress and place youth at risk of academic and social difficulties,
as well as adult psychopathology. Specific phobias have multi-determined etiologies. Genetics, learning
history, modeling, parenting, and evolutionary preparedness have all been implicated in their develop-
ment. Assessments should ideally be multi-method (e.g., diagnostic interviews, questionnaires,
behavioral approach tasks) and multi-informant (e.g., child, parent, and teachers). The information
gathered during the assessment is then used to determine the most appropriate treatment approach.
Cognitive behavioral treatments, particularly exposure-based treatments including systematic desen-
sitization, reinforcement practice, and modeling and participant modeling are considered efficacious
for the treatment of childhood-specific phobias. A one-session treatment (OST) package incorporating
all of these cognitive behavioral procedures is currently an evidence-based treatment for treating this
condition. It is expected that a parent augmented OST will further enhance treatment outcomes for
phobic youth.
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Separation Anxiety Disorder
Aleta G. Angelosante, Magdalena A. Ostrowski, and Rachel R. Chizkov
Abstract Separation anxiety disorder (SAD) is one of the most commonly diagnosed anxiety disorders
among children presenting for treatment. A child with SAD experiences excessive anxiety concerning
separation from home or from caregivers as well as persistent, unrealistic worry about harm to self or
loved ones. Fears may manifest as an unwillingness to leave home, reluctance to be alone, physical
complaints around separation, and frequent reassurance seeking regarding safety. This chapter provides
a review of the current literature regarding the course and etiology of SAD, with a focus on genetic
studies, environmental factors, and parenting. The link between childhood SAD, panic disorder, and
other forms of psychopathology in adulthood is also considered. Assessment and treatment of SAD are
discussed, with a review of the empirical evidence for the use of traditional cognitive-behavioral ther-
apy (CBT), camp-based CBT, modified parent–child interaction therapy, and psychopharmacological
treatments. Research on assessments and treatments specifically for SAD has been scarce. Given the
relatively high prevalence of this disorder, and its role as a predictor of later psychopathology, further
study is warranted. Future research might examine treatments designed specifically for SAD or recruit
a subject pool that would allow for independent investigation of results for those with SAD within a
larger heterogeneous anxiety sample. Furthermore, additional attempts to understand SAD as a risk
factor may lead to prevention of adult psychopathology in these children.
Keywords Separation anxiety disorder • Children • Etiology • Course • Cognitive-behavioral therapy

• Parent–child interaction therapy
Case Scenario
Melissa is a 9-year-old girl in the 4th grade whose parents brought her in for an evaluation because
of her fears of being away from them. Before going to school each morning, she checks in with her
mother about who is picking her up and where she should wait. Her mother reminds her that the plan
A.G. Angelosante (*)

NYU Child Study Center, NYU Langone Medical Center, New York, NY 10016, USA
e-mail: aleta.angelosante@nyumc.org
M.A. Ostrowski
Kean University, North Avenue, Hillside, NJ 07205, USA
R.R. Chizkov
Department of Child and Adolescent Psychiatry, NYU Langone Medical Center, One Park Avenue, 7th Floor, New
York, NY 10016, USA
130 A.G. Angelosante et al.
is always the same and that the schedule is on the refrigerator, but Melissa says she “just wants to be
sure.” Last week, when Melissa’s mother got stuck in bad traffic on the way to pick her up and arrived
20 minutes late, she found Melissa in tears in the principal’s office. When she saw her mother, Melissa
hugged her tightly and said, “I thought you were dead!” Melissa has many friends, and although she
will go to their homes, she much prefers to have play dates at her house. Her friends have recently
begun having sleepovers for their birthday parties; Melissa will go to the party but will leave before
everyone goes to bed. She tells her friends that her mom will not let her stay, but in truth, she is too
nervous to sleep anywhere other than her own house. Each night, Melissa’s mom reads to her and then
must stay in her room until Melissa falls asleep. If Melissa wakes in the middle of the night, she will
immediately go into her parents’ room and either crawl into their bed or make a bed of blankets and
sleep on their floor. Melissa was invited to go with her best friend to Disney World for a long weekend;
although she was worried about it, she desperately wanted to go and said yes. The night before she
was going to leave, she told her mother that she did not think she could go. She continued to cry all
night and could not fall asleep. When her friend’s family arrived to pick her up, she clung to her
mother and refused to let go. The family left without Melissa, worried they would miss their flight.
Melissa felt awful for having disappointed her friend and was extremely embarrassed about “acting
like a baby.”
Separation anxiety is typical in infants between the ages of 8 and 14 months. Infants in this age range
will often cry or become agitated when their parent or caregiver leaves. This behavior may wax and
wane up until age 3 or 4 years when children are typically able to calm down shortly after the act of
separation [1]. Separation anxiety becomes a disorder when the fear is excessive for the child’s devel-
opmental age and begins to interfere with his/her daily functioning. The hallmark fear for children
with separation anxiety disorder (SAD) is a developmentally inappropriate fear that something bad
will happen to them (e.g., they will get kidnapped) or to their parents (e.g., they will get in a car acci-
dent or murdered) while they are apart. Children with SAD are often described as “clingy” and may
stay extremely close to their parents even when they are nearby. For example, the child may not want
to be on a separate floor of the house or even in a different room.
SAD is most often diagnosed in young children and therefore is classified within the “Disorders
first recognized in infancy or childhood” section of the DSM-IV TR [2]. Diagnostic criteria for SAD
state that symptoms must be present for at least 4 weeks and include the following: the child must
experience excessive anxiety concerning separation from home or from caregivers; persistent, unrealistic
worry about harm to self or loved ones; unwillingness to leave home, attend school, or go on outings;
reluctance to be alone, especially at night; physical complaints when separation occurs or is antici-
pated; and frequent seeking of reassurance regarding safety of self and loved ones. Some researchers
have found differences in symptom presentation across development. For example, Francis and
colleagues [3] found that young children were more likely to have nightmares and bedtime separation
fears, children in middle childhood were more likely to display distress when having to physically
part from their parents (e.g., to attend school), and preteens and adolescents were most likely to expe-
rience significant somatic symptoms.
At the time of this writing, DSM-5 is undergoing field trials to test updates to various disorders.
For SAD, the restriction of this disorder exclusively to childhood and adolescence is being lifted, and
the presence of adult SAD is being recognized. Towards this end, SAD is being moved from the
“Disorders first recognized in infancy or childhood” section to the “Anxiety Disorders” section. As a
result, the language of the criteria is being changed throughout to more accurately describe the pre-
sentation of the disorder in both children and adults. For example, the word “child” is replaced with
Separation Anxiety Disorder 131
“individual,” reluctance to go to work is added to the criterion regarding unwillingness to leave home
or attend school, and the phrase “major attachment figures” replaces “parents or caregivers” throughout,
since for those with adult SAD, the anxiety is often regarding separation from spouses, partners, or
children (www.dsm5.org).
Prevalence
SAD has a lifetime prevalence of 5.2 % [4] with the disorder being more common at younger ages.
Peak age of onset for SAD appears to be between ages 7 and 9 [5]. Of youth who will develop SAD,
75 % will do so by age 10 and 90 % will do so by age 13 (Kessler et al., 2005) [4]. SAD prevalence
appears to decline with age as findings show rates of 4.1 % in 9–10-year-old children, 1.2 % in 11-year
olds, 0.6 % in 12-year olds, and progressively lower rates throughout adolescence. A study by Costello
and colleagues [6] found a 3-month prevalence rate of 1 % in youth ages 9–16. SAD is also one of the
most common anxiety disorders in children presenting for treatment. Last and colleagues [7] examined
73 consecutive admissions to their outpatient child anxiety-treatment clinic and found that SAD was
the most common disorder, with approximately 1/3 of all children seeking treatment meeting criteria
for the disorder. Reports of gender differences in SAD are mixed; several studies [7–10] found SAD
to be more prevalent in girls, while others [3, 5] found no gender differences.
Course
There is significant evidence that SAD often remits in childhood or adolescence with persistent SAD
being related to higher levels of comorbid externalizing behaviors. In a community sample of youth
ages 8–16 followed over an average of 18 months, only 20 % of SAD cases persisted over the course
of the follow-up period; at follow-up, 63 % of children diagnosed with SAD were new cases [10]. Last
and colleagues [5] reevaluated a sample of anxious youth annually for 3 years and found that those
diagnosed with SAD had the highest recovery rate (80 %).
Despite this high remission rate, SAD appears to be a risk factor for the development of other anxiety
disorders in adolescence [11] and adulthood [12]. One study interviewed adults currently diagnosed
with anxiety disorders about their history of symptoms and diagnoses; those who reported a history of
SAD were more likely to have lifetime diagnoses of two or more additional disorders, including other
anxiety disorders, depressive disorders, or substance use disorders. This suggests that SAD in childhood
may be a vulnerability factor for the development of later psychopathology [12]. Another study examined
the retrospective report of adults with panic disorder, from both referred and non-referred samples
[13]. Both overanxious disorder and SAD during childhood independently predicted panic disorder in
adulthood. In a follow-up study of the non-referred adults, Biederman and colleagues [14] found that
SAD, along with specific phobia and social phobia, each independently predicted panic disorder.
Link Between Sad and Panic Disorder
In 1964, Donald Klein first postulated that separation anxiety in childhood was specifically linked to
the development of panic disorder (with or without agoraphobia) in adulthood [15]. Since that time,
many studies have examined the possibility of this link, which has resulted in mixed findings.
Some studies examined retrospective reports of adults with panic disorder, while others examined
the offspring of adults with panic disorder to see if there is a high rate of SAD. Lewinsohn et al. [16]
provided evidence for a specific link, using retrospective reports. It was found that children with SAD
were more likely than children without SAD to develop panic disorder and depressive disorders in
adulthood but were not more likely to develop other anxiety disorders. Another retrospective study
found that retrospective reports of childhood SAD were associated with greater rates of adult panic
disorder; however, it was also associated with nearly equal rates of adult social phobia [17]. Thus,
retrospective studies have not provided unequivocal evidence as to whether the link between SAD
and panic disorder is unique.
Others have looked at correlates of both SAD and panic disorder, such as ventilatory physiology.
Hypersensitivity to CO2 inhalation is a frequently observed biological correlate of panic disorder in
adults [18–20]. Similarly, Pine and colleagues [21] found that children with SAD and to a lesser
degree those with generalized anxiety also showed CO2 hypersensitivity; no association was seen for
social phobia. Another study examined this phenomenon by conducting a CO2 challenge in the off-
spring of matched samples of parents with and without panic disorder [22]. This study found that
offspring of parents with panic disorder who met criteria for SAD had a threefold increase in the rate
of panic attacks in response to CO2 challenge as compared to offspring without SAD and to children
with SAD whose parents did not have panic disorder. This group of children also showed increased
rates of panting during the challenge, similar to panting behaviors displayed by adults with panic
disorder in other studies, suggesting that youth with SAD who display hypersensitivity to CO2 may be
at increased risk for developing panic disorder in adulthood.
Several longitudinal studies have examined the course of SAD over time, specifically investigating
this hypothesized link between childhood SAD and adult panic disorder. Pine and colleagues [23]
examined a large sample of youth who had undergone psychiatric interviews between the ages of 9
and 18 (Time 1). This sample was reassessed 2 years later (Time 2) and again 10 years later (Time 3).
SAD at Time 1 was significantly related to “fearful spells” (which closely resemble panic attacks) at
Time 3. Although Time 1 SAD was positively related to a diagnosis of panic disorder at Time 3, the
relationship did not reach statistical significance. Aschenbrand and Kendall [11] conducted a follow-up
study of individuals who had participated in an anxiety-treatment program as children and adoles-
cents, on average 7.4 years previously. Given the hypothesized link between SAD and panic disorder,
they examined whether those youth who presented with SAD would be more likely to meet criteria
for panic disorder than those who had presented with other anxiety disorders (e.g., social phobia or
overanxious disorder). Both treatment successes and treatment failures were included. While a history
of SAD was predictive of later anxiety disorders, it was not specifically predictive of panic disorder.
Comorbidity
Anxiety disorders are highly comorbid with one another, and it is in fact more likely for a child to
meet criteria for more than one disorder than for just a single disorder. Last and colleagues [24] found
that 79 % of youth with SAD met criteria for an additional disorder; in this study, those with SAD
were most likely to have a concurrent diagnosis of overanxious disorder or major depression. More
recent studies of SAD have found concurrent comorbidity of 20 % with generalized anxiety disorder
and depressive disorders [25]. In addition to being comorbid with other anxiety disorders, SAD is
most often associated with school refusal behavior; this is understandable given that school is the one
place where children are required to be that separates them from their parents. One study of children
who engaged in school refusal behavior found that SAD was the most common diagnosis, occurring
in 22 % of the sample [26]. As discussed previously, there is a hypothesis that SAD leads to future
panic disorder; one recent study examined youth who met criteria for both SAD and panic disorder
concurrently [27]. Youth with comorbid SAD and panic disorder had a later onset of SAD and a
greater number of additional comorbid diagnoses than those with only SAD.
Etiology
There are many pathways towards the development of SAD. In this section, we will review the genet-
ics and biological vulnerabilities, parenting styles, and early developmental factors that appear to be
influential in the onset of SAD.
Genetic and Biological Vulnerabilities
Family studies have revealed a genetic link for SAD. Weissman and colleagues [28] found significantly
higher rates of anxiety disorders, particularly SAD, in the offspring of parents with anxiety and
depressive disorders. Similarly, Biederman and colleagues [29] found increased rates of SAD in the
offspring of parents with major depression, panic disorder with agoraphobia, or both, when compared
to normal controls. Feigon and colleagues [30] examined separation anxiety symptoms, zygosity (i.e.,
physical similarity standing in for DNA markers), and shared environmental factors in a sample of
twin pairs and their siblings. In the complete sample, genetics accounted for nearly 50 % of the vari-
ance, while shared environment factors accounted for about 20 %. However, this relationship was
moderated by sex (with genetic influences greater in girls than boys, environmental factors greater in
boys than girls) and by age (with genetic influences increasing with age). While this may suggest that
shared genetics is more important than shared environmental factors, they also found that twins had a
greater degree of shared environment variables than non-twin siblings, complicating interpretation of
these data. Cronk and colleagues [31] also examined heritability and environmental influences in
SAD by assessing the zygosity and shared environmental variables in female twin pairs. Unlike
Feigon [30], they used categorical diagnostic criteria, rather than dimensional separation symptoms,
as their measure of SAD. They found that genetics accounted for 62 % of the variance and shared
environment accounted for 20 % of the variance, when examining participants who met full diagnos-
tic criteria for SAD. Topolski and colleagues [32] investigated both genetic and environmental
influences finding that genetics only accounted for 4 % while shared environment accounted for 40 %
of the variance associated with an SAD diagnosis.
As our understanding of neurobiology grows, researchers have been examining the neurobiologi-
cal bases of psychopathology. One recent study examined hypothalamic–pituitary–adrenocortical
(HPA) system function in youth with SAD by measuring cortisol levels over the course of an experi-
mental manipulation; all samples were collected in the afternoon [33]. Consistent with the study
hypothesis, it was found that children diagnosed with SAD had higher cortisol secretion across all
study timepoints (and therefore increased HPA activity) than controls. However, an additional hypoth-
esis that children with SAD would also show additional cortisol increase following a separation para-
digm (in which the child’s mother left him/her alone with an unfamiliar examiner for a few minutes)
was not confirmed; a ceiling effect could account for this lack of finding.
Parenting
Multiple studies have found that parents of anxious children tend to be overprotective [34], overly
intrusive [35], and less likely to grant psychological autonomy [36] when compared with parents of
non-anxious children. One study, directly examining adolescents’ perceptions of psychological and
behavioral control found that teens who endorsed high levels of separation anxiety symptoms reported
that their parents were increasingly controlling and demanding and less sensitive to their needs [37].
Of note, however, is that the reports of adolescent anxiety symptoms and of parental behaviors were
based on adolescent report and therefore subject to reporting bias. Additional studies are needed to
examine whether this relationship would hold in a sample of youth diagnosed with SAD and with
observational evidence of parental control.
As noted previously, anxious youth often have parents who are anxious themselves, and these parents
appear to both model and reinforce anxious behaviors, such as avoiding stressful or potentially
dangerous situations [38]. One longitudinal study examined the role of parental anxiety on the devel-
opment of SAD [39]. In a study of over 900 9-year-old children in New Zealand, mothers’ reports of
their own fear of being alone positively predicted children’s separation anxiety symptoms 2 years later.
Early Developmental Factors
Several studies have examined the putative role of early experiences and behavioral tendencies in the
development of SAD. One study examined whether early stranger anxiety could differentiate youth
with SAD from those without [40]. This study found that parents of children with SAD (ages 4–14)
described their children as having greater stranger anxiety as toddlers than parents of youth without
SAD. While these data are compelling, it should be noted that this was a retrospective report of
stranger anxiety; such parental report could be biased by the child’s current separation anxiety. In
addition, the retrospective report was simply one dichotomous variable, asking mothers to indicate
whether or not the child had experienced stranger anxiety as a toddler. Additional prospective data
would be useful here, as would dimensional measures that provide greater variability. Some research-
ers have wondered about the role that early separation experiences may have on the development of
later separation anxiety. Poulton and colleagues [39] found that, in fact, early planned separations
from parents (e.g., dropping child off at day care) were actually related to fewer separation anxiety
symptoms in later childhood and adolescence. While this study offered prospective data, separation
anxiety was examined only at a symptom level; it is not yet clear if these planned separations could
actually act as a preventative measure against the development of SAD.
Assessment
General assessment of anxiety disorders is covered elsewhere in this volume. Here we will focus only
on evaluations that specifically assess for symptoms of SAD. Questionnaire measures are not sufficient
for diagnosing disorders, but they can provide valuable information about specific symptoms and/or
their severity. While there are currently no questionnaires that assess solely for symptoms of SAD,
several child anxiety questionnaires have subscales that are designed to reveal SAD symptoms.
Multidimensional Anxiety Scale for Children
The Multidimensional Anxiety Scale for Children (MASC) is a 39-item questionnaire normed for use
with children ages 7–19 [41]. Both child-report and parent-report versions are available. The MASC
assesses overall anxiety as well as four empirically derived domains of common childhood anxiety,
one of which is called “separation anxiety/panic.” This 9-item scale measures specific fears and
worries that a child with SAD or panic might have using items such as “the idea of going away to
camp scares me.” The MASC has demonstrated adequate test-retest reliability and differentiates
children with anxiety disorders from both those without any psychiatric disorders and those with
psychiatric disorders other than anxiety [42].
Screen for Child Anxiety Related Emotional Disorders
The Screen for Child Anxiety Related Emotional Disorders (SCARED) was developed by Birmaher
and colleagues [43] based on DSM-IV definitions of four of the most common anxiety disorders in
children and adolescents: social phobia, SAD, panic disorder, and generalized anxiety disorder.
It also contains a scale that assesses for school phobia, which, while not an official DSM-IV diagno-
sis, is a fear that is commonly seen in children with a wide array of diagnoses. The SCARED is
comprised of 41 items on a 3-point Likert scale and has identical but separate versions for child-
report and parent-report (only substituting you/your child). The SCARED has good internal consis-
tency and reliability [43] and has also been found to have good reliability and validity when used
in a clinical sample [44]. Unlike the MASC which combines symptoms of SAD and panic disorder
into one scale, the SCARED has a separate 8-item scale specifically assessing symptoms of SAD,
including items “I follow my mother or father wherever they go,” and “I don’t like to be away from
my family.”
Spence Children’s Anxiety Scale
Like the SCARED, the Spence Children’s Anxiety Scale (SCAS) was developed to assess specific
DSM-IV factors of anxiety [45]. The SCAS is designed for use with children ages 8–12 and uses a
4-point Likert scale. It consists of 44 items, 6 of which are filler items asking about positive attributes
of the child that are not factored into the total score or subscales; these items are meant to reduce the
possibility of a negative response bias. In addition to a total anxiety score, the SCAS provides several
subscale scores including a 6-item separation anxiety subscale that asks questions such as “I worry
about being away from my parents,” or “I feel scared if I have to sleep on my own.” The SCAS has
demonstrated good internal consistency, retest reliability, and convergent and discriminant validity
[45]. As part of the move towards dimensional rather than categorical definitions of disorder in the
new DSM-5, a 10-item scale from the SCAS has been developed that focuses specifically on SAD and
is applicable across the life span. This measure is being assessed as part of the field trials and may be
included in the DSM as a way of noting SAD severity.
Separation Anxiety Inventory
The Separation Anxiety Inventory (SAI) is a 12-item, 5-point Likert scale measure of separation anxiety
symptoms in children that can be completed by the parent or the child (cf. [46]). Currently, it is not
routinely available as it was developed as part of an unpublished thesis and appears to only be used
by the research group that developed it. It demonstrated good reliability in one study [46], but more
research is needed to determine if this will begin to fill the void of SAD measures.
Treatment
Many types of interventions are available for the treatment of SAD. Here, we will describe empirically
supported treatments for SAD including traditional cognitive-behavioral approaches, novel behavioral
approaches, and psychopharmacology.
Cognitive-Behavioral Approaches
In reviewing the literature, empirical evidence for treatment approaches for children with SAD is
largely taken from trials conducted with groups of children with heterogeneous anxiety diagnoses.
Randomized controlled studies of anxiety treatment in youth have primarily focused on a cognitive-
behavioral therapy (CBT) approach. Psychoeducation, cognitive restructuring, exposure, modeling,
relaxation strategies, and homework assignments are components of the CBT protocols for anxious
youth. Recently, Silverman et al. [47] used the criteria of Chambless et al. [48] and Chambless and
Hollon [49] to evaluate the evidence for various treatment approaches. According to these criteria,
individual cognitive-behavior therapy (ICBT) and group cognitive-behavior therapy (GCBT) were
classified as probably efficacious treatment approaches for children with anxiety disorders, including
but not specific to SAD. Additional studies of CBT with various family components (FCBT) were
assessed for which the evidence was found to be mixed. As children diagnosed with SAD were included
in a majority of CBT trials [50–63], results provide evidence for the efficacy of these approaches for
children with this disorder; however, none of those studies focused exclusively on outcomes for children
diagnosed with SAD, nor did they examine the specific outcomes of those diagnosed with SAD. These
treatments and their supporting evidence will be discussed in greater detail in Chap. 13.
The trials described above all include participants with diagnoses of SAD; however, results for
children with that particular diagnosis were not reported in isolation from the rest of the group.
Recently, a randomized controlled trial was conducted to evaluate a protocol specific to SAD, which
includes CBT and parent-training components [46]. Within this trial, 43 children ages 5–7 were
randomly assigned to either a wait-list or treatment condition. The treatment protocol included a com-
bination of individual and family sessions, with SAD-specific psychoeducation, in addition to cogni-
tive restructuring, exposure, and behavior management training. It was reported that 76 % of children
receiving treatment were free of an SAD diagnosis 4 weeks after treatment completion, compared to
13.6 % of children assigned to the wait-list condition. It was noted that the disorder-specific nature of
the protocol allowed for the inclusion of more severe SAD cases and that the effects of treatment were
larger than those reported in meta-analyses of treatments for groups with various anxiety disorders.
These results are promising, and further evaluations of SAD-specific protocols are warranted in order
to determine whether such an approach leads to greater treatment gains than nonspecific CBT inter-
ventions for pediatric anxiety.
Preliminary evidence suggests that treatment protocols aimed at training parents to manage their
child’s anxiety may be beneficial for children diagnosed with anxiety disorders [64]. In a multiple base-
line design, six families of children with SAD participated in a parent-training intervention with the
goal of training parents to implement CBT methods with their children. Five of the six children no longer
met SAD criteria following the intervention [65]. These results suggest that parent-training-based
interventions may be particularly useful in the treatment of children diagnosed with SAD.
Novel Behavioral Treatments
While standard CBT for SAD has some empirical support, the unique features of SAD (e.g., opposi-
tionality) have led clinical researchers to investigate innovative behavioral interventions to treat this
disorder.
Parent–Child Interaction Therapy
Parent–Child Interaction Therapy (PCIT) is an approach that has been effective in treating childhood
disruptive disorders and has provided a solid foundation for a novel approach to the treatment of
separation anxiety. The overarching goal of PCIT is to improve child and family functioning through
effective behavior management while fostering a warm and responsive parent–child relationship
[66]. Standard PCIT includes two phases conducted during an average of 13, 1-hour sessions. The
Child-Directed Interaction (CDI) phase focuses on behavioral management skills whereas the
Parent-Directed Interaction (PDI) phase promotes clear and effective communication methods.
Parents are coached during these phases by a therapist using a one-way mirror and a “bug-in-the-ear”
[67]. A pilot study of three children (6–8 years old) was conducted to test the application of standard
PCIT methodology to the treatment of children with SAD [68]. All three cases were considered
“recovered” meaning that none of these cases met criteria for SAD following six to seven treatment
sessions [68]. However, a slightly larger pilot study (10 participants, ages 4–8) found that while
some improvement in SAD severity was reported, nonclinical levels were not achieved [69].
As a result of the potential utility of standard PCIT in the treatment of SAD, the Center for Anxiety
and Related Disorders at Boston University developed an adaptation of PCIT to address SAD con-
cerns more specifically [70]. The Bravery-Directed Integration (BDI) phase was developed and added
to the existing CDI and PDI phases. The BDI phase provides psychoeducation to parents as well as
instruction on effective separation exposure practice in order to decrease avoidance. In an RCT of the
modified PCIT for SAD, 34 children were randomized to either modified PCIT or wait-list control.
Significant improvements from pre- to post-intervention in SAD severity were reported, along with
improvements in academics, sibling behavior, and parenting stress [70]. Upon further investigation,
the modified PCIT protocol may prove to be an effective treatment approach to address the specific
needs of families of children with SAD.
Summer Camp
In emphasizing the importance of disseminating and implementing cognitive-behavioral interven-

tions for youth with anxiety disorders, camp-based CBT has been highlighted for its accessibility and
efficiency in treating this population [71]. Summer treatment programs for externalizing disorders
have been supported by empirical studies [72, 73], and presently similar intensive protocols are being
evaluated for internalizing disorders. Among these protocols is Camp CARD (Center for Anxiety and
Related Disorders), a 1-week intensive group cognitive-behavioral intervention for children with SAD
[74]. The treatment’s authors propose that the camp utilize creative and novel techniques in a social
context in order to implement traditional, research-supported CBT components within a developmental
model. Psychoeducation, somatic anxiety management, cognitive restructuring, problem solving,
exposure, relapse prevention, and a parent component serve as the foundation of the treatment
approach. Differential reinforcement and shaping of behavior during in vivo separation exposures
occurs throughout the 7-day intervention, as parental involvement is faded. A pilot study of the Camp
CARD program was recently conducted with five girls with a principal diagnosis of SAD. Clinically
meaningful reductions in SAD severity were noted for all participants; three participants no longer
met criteria for a diagnosis of SAD immediately after the intervention, and no child met SAD criteria
at the 2-month follow-up [74]. Improvements in parent- and child-reported separation anxiety as well
as fear and avoidance were also reported. This preliminary evidence suggests that this intensive camp-
based protocol has promise in the treatment of SAD; further research is needed to examine its efficacy
and effectiveness with larger samples and community-based programs.
Psychopharmacological Treatment
Several pharmacological agents are also empirically supported for the treatment of anxiety disorders
in youth, including SAD. One study by Walkup and colleagues [75] examined youth ages 6–17 with
SAD, generalized anxiety disorder, or social phobia. Children treated with fluvoxamine [a selective
serotonin reuptake inhibitor (SSRI)] had fewer anxiety symptoms and better overall functioning at the
end of 8 weeks than the placebo group. Overall, 76 % of those treated were much improved or very
much improved by the end of the 8 weeks. However, results were not broken down by disorder, such
that the specific effects on SAD in particular are not known. Other SSRI studies [76–78] had similar
positive results for treatment of anxiety in youth, though SAD was not examined separately.
While SSRIs are most often studied and prescribed currently, earlier studies investigated tricyclic
antidepressants (TCAs). Gittelman-Klein and Klein [79] conducted a small RCT for children who
were exhibiting school refusal behavior, which the authors attributed primarily to separation anxiety
concerns. Children who were prescribed imipramine were significantly more likely to return to school
and had better overall functioning after 6 weeks than those who had been prescribed the placebo.
However, later studies [80–82] failed to find TCAs superior to placebo when treating school refusal/
SAD. It should be noted that in these early studies, as with the more recent SSRI studies, SAD was
not evaluated independently. In these studies, school phobia or school refusal was seen as a proxy for
SAD, and in the SSRI studies, the samples are comprised of youth with a variety of anxiety disorders
including, but not limited to, SAD. Future research should examine the specificity of psychopharma-
cological treatment for SAD.
Melissa’s Story: Treatment and Outcome
After the Disney World incident, Melissa’s parents decided to bring her to a psychologist for help.
Melissa met with a psychologist who specialized in CBT. Melissa first learned about recognizing her
emotions and distinguishing physiological, emotional, and cognitive responses to anxiety. She was
taught skills to manage her anxiety, such as relaxation and arguing back with her anxious thoughts
(e.g., when thinking, “Mom is late—she must have gotten into an accident,” she can remind herself
that her mother has never been in a serious accident and people run late for many, non-tragic, rea-
sons). Finally, she engaged in a set of gradual in vivo exposure exercises both with her therapist and
on her own for homework. In session, Melissa started with easy exposures, such as having her mother
leave the clinic to get a cup of coffee, and worked up to more challenging ones, like walking alone to
a bookstore two blocks away and meeting her mother there. Her homework took a similar path, from
easy exercises like having her mother leave her bedroom while she was still awake and resisting the
urge to go to her parents’ room in the middle of the night, to having her mother purposefully pick her
up late from school, and finally to sleeping over at her best friend’s house. The course of treatment
took about 14 weeks, and Melissa and her parents reported that she was no longer fearful of bad
things happening to her parents and was able to successfully calm herself down on the few occasions
that she did become nervous.
Summary
SAD is a common disorder of childhood characterized by the fear that bad things will happen to the
child and/or his/her parents, which often manifests itself in difficulty being away from parents or from
home. While it seems clear that SAD in childhood is a risk factor for psychopathology later in life,
little is known about what other specific variables may contribute to what that later psychopathology
may be. Additional prospective studies of youth with SAD are needed in order to understand why
SAD is a risk factor and how to use this information to prevent adult psychopathology in these
children. Overall, very little research has been conducted on the assessment and treatment of SAD
specifically, nor have specific SAD results been examined within the context of larger anxiety studies.
Future intervention studies would do well to examine treatments designed specifically for SAD or, in
larger heterogeneous anxiety samples, to recruit a subject pool large enough to look at results for those
with SAD independently. The development of additional SAD-specific assessment tools would also
be valuable; there is only one, relatively new, questionnaire measure currently available that is
specifically aimed at measuring symptoms of SAD. This is unusual, in that other anxiety disorders
(e.g., social phobia, generalized anxiety disorder, and obsessive-compulsive disorder) have multiple
questionnaire measures available both for the pediatric and adult populations. Such measures would
assist in screening youth for SAD but could also be useful for measuring treatment effects. Given the
relatively high prevalence of this disorder, and its role as a predictor of later psychopathology,
improved understanding of SAD is needed.
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Panic Disorder
Aleta G. Angelosante and Magdalena A. Ostrowski
Abstract Panic disorder with or without agoraphobia is characterized by recurrent panic attacks, some
of which occur without apparent warning or trigger, and ongoing worry about future attacks. While
panic disorder is very rare in school-age children, incidence rates increase dramatically among adoles-
cents. When panic disorder includes related symptoms, such as agoraphobia, diagnostic decision-mak-
ing can be complicated; however, a differential diagnosis may be determined by considering the nature
of the feared consequence. In the chapter that follows, the current literature regarding the course and
etiology of child and adolescent panic disorder will be reviewed, with a focus on genetic studies, anxi-
ety sensitivity, carbon dioxide sensitivity, and the link between panic disorder and childhood separation
anxiety disorder (SAD). Assessment and treatment of panic disorder in youth will be discussed with a
review of the empirical evidence for the use of traditional cognitive-behavioral therapy, an intensive
treatment protocol, and pharmacological treatments. Research on panic disorder in children and ado-
lescents is still in its infancy; suggestions for future research include additional prospective studies of
the purported link between early SAD and panic and investigation into other risk factors for the devel-
opment of panic disorder. As described in the chapter, there is also a relative lack of research on the
treatment of pediatric panic disorder; additional studies are necessary to establish a gold standard of
treatment in this age group and to elucidate factors which may influence treatment response.
Keywords Panic disorder • Children • Adolescents • Etiology • Course • Cognitive-behavioral

therapy • Intensive treatment
Case Scenario
Joey is a 12-year-old boy in the 7th grade who was brought for an evaluation by his parents. They
reported that his symptoms began during the summer when Joey became overheated and felt dizzy
while playing soccer with his friends. The previous night, the news had been full of safety information
about heat stroke and dehydration. As a result, Joey became incredibly worried that these feelings
meant he was dehydrated and might suffer heat stroke. He began to hyperventilate and shake and
A.G. Angelosante (*)

NYU Langone Medical Center, One Park Avenue, 7th Floor, New York, NY 10016, USA
e-mail: aleta.angelosante@nyumc.org
M.A. Ostrowski
Kean University, North Avenue, Hillside, NJ 07205, USA
144 A.G. Angelosante and M.A. Ostrowski
complained that his chest hurt. His friends called 911, and an EMS team arrived and took Joey to the
hospital. Shortly after arriving, all of his symptoms had subsided, though he was still anxious and
concerned about the incident. The doctors ruled out any medical conditions and suggested that he had
a panic attack. Joey refused to play soccer with his friends for the rest of the summer. When he went
outside, he made sure that he always had his cell phone and a bottle of water with him. A few weeks
later, while sitting on his couch playing videogames, Joey felt the same sensations—his heart was
racing, he could not catch his breath, and he felt overheated and dizzy. Joey was sure something was
horribly wrong and thought he might even be dying. He called his mother, but she was in a meeting
and did not answer the phone. By the time she called him back, 20 minutes later, the symptoms were
almost completely gone. He worried that if it could happen while he was on his couch, it could happen
anywhere. He started insisting on sitting on the aisle at the movies, in case he needed to get out; one
time, when the theater was crowded and he was forced to sit in the middle, he worried so much about
whether or not he would be able to get out that he started to feel panicky and left the theater. When he
returned to school in the fall, he continued to keep a bottle of water and his cell phone with him at all
times. His parents expressed concern that he is limiting his activity for fear that these symptoms will
return. For example, his gym teacher noticed that he has forgotten his gym clothes or sneakers several
times, requiring him to sit out of gym.
A panic attack is a feeling of intense fear and physiological arousal; the peak intensity is reached in
approximately 10 minutes, and the sensations tend to subside within 20–30 minutes. Symptoms of a
panic attack include increased heart rate, increased breathing rate, hyperventilation, shaking, sweat-
ing, dizziness, muscle tension, headache, blurred vision, dissociation, and feeling of unreality. In
addition to these physiological symptoms, panic attacks include cognitive symptoms such as the
belief that one is dying, going “crazy,” or about to lose control. Panic attacks are relatively common
and approximately 23 % of people will experience an isolated panic attack at some point in their lives
[1]. Usually, these are cued panic attacks, meaning that the person becomes scared in the face of a
frightening situation (e.g., when faced with a phobic stimuli or after enduring a traumatic event).
Uncued panic attacks, the hallmark of panic disorder, are those which seemingly come “out of the
blue.” Panic disorder can occur either with or without agoraphobia. Those with agoraphobia will fre-
quently avoid situations that they fear may cause a panic attack or would be difficult or embarrassing
to escape if a panic attack did occur. For example, they may need to sit on the aisle in a theater or
avoid subways, planes, shopping malls, crowded places, or places where they feel “trapped.” Those
without agoraphobia experience significant anxiety about the possibility of additional panic attacks
and may engage in safety behaviors in the hopes of either preventing future attacks (e.g., carrying
water or an anxiolytic medication) or preventing harm should an attack occur (e.g., insisting on hav-
ing a cell phone with them at all times) but do not engage in any avoidance of places or situations. In
clinical samples, there is a very high co-occurrence of agoraphobia with panic disorder [2]. In non-
referred samples, however, panic symptoms more frequently occur without agoraphobia [3]. This
disparity suggests that panic disorder with agoraphobia is more impairing than panic disorder alone,
leading these individuals to seek treatment. Most of the research in panic disorder combines those
with and without agoraphobia, so the abbreviation PD will be used throughout this chapter to refer to
both of these types, except when referring to studies which purposefully differentiate between or
compare panic disorder with, and panic disorder without, agoraphobia.
The DSM-IV TR [4] criteria for panic disorder states that recurring, unexpected panic attacks must
be present and be followed by at least 1 month of persistent concern about (1) having additional
attacks, (2) worry about the implications of the attack or its consequences (e.g., losing control, having
Panic Disorder 145
a heart attack, “going crazy”), or (3) a significant change in behavior related to the attacks. Panic
disorder with agoraphobia includes the above but also significant anxiety about being in places or
situations from which escape might be difficult (or embarrassing) or in which help may not be avail-
able in the event of having a panic attack or panic symptoms. Such situations are avoided (e.g., travel
is restricted) or else are endured with marked distress about having a panic attack or panic symptoms
or require the presence of a companion (aka a safe person). The panic attacks cannot be caused by
medical issues (e.g., a thyroid disorder) or substance abuse. They also cannot solely occur in the pres-
ence of a feared object (e.g., specific phobia) or situation (e.g., while separating from a parent).
Accurate diagnosis of panic disorder can often be a challenge since the symptoms show significant
overlap with those of other pediatric anxiety disorders. First, the panic attacks observed in individuals
with panic disorder must be differentiated from those experienced in the context of other anxiety disor-
ders. Panic attacks can occur in the face of any feared situation and, therefore, may be present in any
anxiety disorder. However, as mentioned earlier, to be considered symptoms of panic disorder, at least
some panic attacks have to be uncued. Second, agoraphobic avoidance must be distinguished from the
situational avoidance observed in other disorders. For example, a child with a specific phobia of vomit-
ing may not like to be away from his parents for fear that he will vomit and they would not be nearby
to take care of him. He may avoid going to school or attending extracurricular activities for fear that he
will vomit in front of his friends. He will likely be overly sensitive to physical sensations, becoming
extremely concerned if his stomach “feels weird” or even if he just feels the sensation of a full stomach.
The main differential to be noted is the nature of the feared consequence. A child with panic disorder
with agoraphobia will fear these same situations, but the feared consequence of, for example, attending
school, is that she will have a panic attack, not that she will vomit. Similarly, symptoms of separation
anxiety disorder (SAD) can resemble those of panic disorder and require differentiation based on under-
standing the feared outcome. A child with SAD will want to have her parent nearby, may have trouble
attending drop-off playdates or birthday parties, may have difficulty attending school, and might com-
plain of somatic symptoms (e.g., stomachache, nausea) when anticipating separations or at the time of
required separations from parents. Such a child may even have panic attacks (or limited symptom
attacks) when it is time to separate from her parents (e.g., if they go out and leave her with a babysitter).
For the child with SAD, however, the feared outcome is not a panic attack but rather that while they are
apart, something catastrophic will occur to either herself (e.g., getting kidnapped) or her parents (e.g.,
getting in a car accident) that will keep them from ever seeing each other again. Finally, it is important
to be able to differentiate panic disorder from anxiety disorder due to a general medical condition or
substance-induced anxiety disorder. The physical symptoms of these disorders, such as accelerated
heart rate and hyperventiliation, can mimic panic symptoms. Therefore, a physical exam is needed to
rule out any medical (e.g., cardiac) syndromes or medications that could cause such symptoms.
Prevalence
Panic disorder has a lifetime prevalence of 4.7 % [5]. Among people who develop PD, 25 % will do
so by age 16 and 50 % by age 24. It is very rare in school-age children, but incidence rates increase
dramatically in adolescence and into young adulthood. For example, in a sample of youth ages 9–16,
Costello and colleagues [6] found an overall 3-month lifetime prevalence of 0.2 % (very low in child-
hood, but increases to 0.5 % in mid-adolescence). Hayward and colleagues [7] found that onset of
panic was related to physiological development rather than chronological age. In a sample of middle
school girls, they found that the onset of panic disorder symptoms significantly increased after the
onset of puberty, regardless of chronological age. Regarding gender differences, while cued panic
attacks occur equally frequently in males and females [8], panic disorder with or without agoraphobia
is more common in females [9].
The lower prevalence rate in childhood is theorized to be related to children’s emerging cognitive
development. While children can certainly experience uncued panic attacks, they appear to attribute
these symptoms to external factors and therefore do not have the cognitive appraisals such as “I am
dying” or “I am going crazy” [10]. This externalizing of symptoms has been tied to Piagetian theory
of cognitive development; children in the preoperational stage of development cannot differentiate
between the self and the world, making them concrete and egocentric, and children in the concrete
operational stage cannot conceptualize hypothetical events. As such, it is not until children reach
formal operational thinking that they can recognize the way thoughts can impact physiological
responses and hypothesize about the future [10]. As a result of the low incident rates of PD in children
as well as a theoretical understanding for why this disorder does not emerge until early adolescence,
most of the research in this area has been in adult samples. Only more recently have researchers begun
to examine the disorder, and its assessment and treatment, in youth.
Course
There is limited information about the course of PD in youth, but there is some information regarding
the course of this disorder in adults. One recent study of adults investigated the course of panic disor-
der with and without agoraphobia separately [11]. They followed a sample of 235 adult patients (Mean
age = 38 years) with either disorder over 3 years, finding that those with panic disorder had a recurrent,
relapsing course while those with panic disorder with agoraphobia had a more chronic course. This
finding is similar to other studies, which found that only 39 % of patients with panic disorder and 17 %
of those with panic disorder with agoraphobia remitted after 1 year. Among those who did remit,
nearly 1/3 relapsed within 1 year [12]. A naturalistic study of adults with panic disorder with or with-
out agoraphobia found that nearly half of those who remitted relapsed within 2 years [13].
Comorbidity
Comorbidity is very high with 50–90 % of youth with PD meeting criteria for at least one additional
psychiatric disorder [2, 14]. Youth with PD have high rates of comorbidity with other anxiety disor-
ders but also with disruptive behavior disorders and mood disorders. In one study of youth with PD,
75 % also met criteria for major depressive disorder, 65 % met criteria for oppositional defiant disor-
der, and 58 % met criteria for attention-deficit hyperactivity disorder [2]. In an epidemiological study
of 13 and 14 year olds, those who had experienced a panic attack were three times more likely to have
contemplated suicide and twice as likely to have attempted suicide than those who had never experi-
enced a panic attack [15].
Etiology
Here, we review several factors that are important in the development of panic disorder including
genetic hereditability, anxiety sensitivity, suffocation hypothesis, and childhood separation anxiety.
Panic Disorder 147
Genetics
Panic disorder has long been found to run in families. In a study of nearly 278 relatives of 41 patients
with PD and 262 relatives of 41 matched controls, 17 % of probands’ relatives met criteria for lifetime
PD as opposed to only 2 % of those in the control group [16]. Another study found that relatives of
both early- (prior to age 20) and later-onset PD had a significantly higher rate of the disorder than
normal controls. Further, relatives of early-onset patients had a 17-fold increased risk, while the risk
in relatives of those with later onset had a sixfold increase, indicating that adolescent onset of PD may
have a stronger familial basis than adult onset [17]. In differentiating familial aggregation of internal-
izing disorders, Goldstein and colleagues [18] found that relatives of patients with PD had a
significantly higher risk for panic attacks than those relatives of either patients with major depression
or controls. Finally, when the relatives of a sample of adults with PD were compared with relatives of
patients with other anxiety disorders (e.g., simple phobias, social phobia), they specifically exhibited
higher rates of PD and not of other anxiety disorders [19].
In addition to these family studies, several twin studies have examined the role of genetics in
adults with PD. One study of a large sample of adult female twins found that genetics accounted for
44 % of the variance regarding risk factors for a panic disorder diagnosis, while individual factors
and shared familial factors accounted for 55 % and 1 % of the variance, respectively [20]. A more
recent study by Hettema and colleagues [21] used a mixed sample of male and female twins to exam-
ine panic disorder and agoraphobia separately and found that genetics accounted for 28 % of the
variance for panic disorder and 36 % of the variance for agoraphobia. Finally, some preliminary evi-
dence from genome-wide association studies have begun to identify specific genetic markers that
may be implicated in the development of panic disorder, though larger studies are required to clarify
these findings [22].
Anxiety Sensitivity
Anxiety sensitivity is a construct which describes increased awareness of physiological symptoms

of anxiety (e.g., increased heart rate, increased respiration, nausea) as well as anxiety regarding the
meaning of those symptoms. In Barlow’s model of panic [23], catastrophic interpretations of these
sensations lead to panic attacks. Not surprisingly, then, several studies have examined the relation-
ship between anxiety sensitivity and panic disorder with or without agoraphobia, though only a few
of these studies have been conducted in the pediatric population (for a review of the link between
anxiety sensitivity and panic disorder in adults, see [24]). Kearney and colleagues [25] found that
youth with PD reported significantly higher anxiety sensitivity than youth with other disorders.
Hayward and colleagues [8] also found that anxiety sensitivity predicted panic attacks in a high
school sample. In another sample of non-referred youth, anxiety sensitivity predicted panic attacks
even after controlling for trait anxiety, general anxiety, and depression [26]. Finally, in a community
sample of African-American youth, anxiety sensitivity, panic symptoms, and panic attacks were
assessed initially (time 1) and then again 6 months later (time 2) [27]. The study team found that
anxiety sensitivity was related to concurrent panic symptoms (i.e., anxiety sensitivity at time 1 was
correlated with panic symptoms at time 1 and anxiety sensitivity at time 2 was correlated with
panic symptoms at time 2). In addition, anxiety sensitivity measured at time 1 differentiated
between those who had ever experienced a panic attack and those who had not, both at time 1 and
time 2 [27].
Childhood Separation Anxiety Disorder
There are mixed findings regarding the potential link between SAD in childhood and panic disorder
in adulthood. Retrospective accounts by adults with panic disorder often include reports of SAD in
their childhood. One study asked women in a community sample to report on their memories of sepa-
ration anxiety symptoms in childhood and found that women with panic disorder recounted significantly
more separation symptoms than those with other anxiety disorders (e.g., generalized anxiety disorder,
phobias; [28]). Another study examined the retrospective report of adults with panic disorder, from
both referred and non-referred samples [29]. Overanxious disorder of childhood and SAD each indi-
vidually predicted lifetime panic disorder with or without agoraphobia, while a history of SAD
uniquely predicted adolescent-onset PD. In a follow-up study of only the non-referred adults in the
previous study, SAD, along with specific phobia and social phobia, each predicted later panic disorder
[30]. Some studies have examined panic disorder with, and without, agoraphobia separately. In a
study of retrospective reports of school refusal and separation anxiety, Delito and colleagues [31]
found that while none of the patients with pure panic disorder reported a history of school refusal or
separation anxiety, 60 % of those with panic disorder with agoraphobia reported those symptoms.
Another larger study found a significant difference in history of separation anxiety symptoms between
those with panic disorder with or without agoraphobia and normal controls; moreover, they also noted
a trend towards differentiation between panic disorder with, and without, agoraphobia, with 17 % in
the latter group reporting a history of SAD symptoms and 21 % in the former group [32]. Despite this
evidence, however, it should be noted that other retrospective reports have not found a significant dif-
ference in separation anxiety symptoms between individuals with panic disorder and those with other
anxiety disorders [33, 34] or with other psychiatric disorders [35]. As such, there is no unequivocal
link between childhood SAD and later panic disorder.
Retrospective reports are obviously flawed in that they rely on patients’ memories of symptoms
which may be influenced by their current symptoms. Prospective studies, which follow subjects for-
ward in time, are more reliable because their symptoms can be verified and documented at each time
point. One longitudinal study supports the link between early SAD and later panic disorder. Pine and
colleagues [36] examined a large sample of youth who had undergone psychiatric interviews at time
1 and were reassessed 2 years later (time 2) and again 10 years later (time 3). SAD at time 1 was posi-
tively related to panic disorder at time 3, though the relationship did not reach statistical significance.
SAD at time 1 was significantly related to “fearful spells” (which closely resemble panic attacks) at
time 3. However, two additional longitudinal studies [14, 37] did not find a relationship childhood
SAD and later PD.
Further evidence for the link between SAD and panic disorder comes from common physiological
markers such as hypersensitivity to carbon dioxide (CO2) inhalation, which has been identified as a
biomarker of panic disorder in adults (described in more detail below). Pine and colleagues [38]
assessed hypersensitivity to CO2 in children with SAD, generalized anxiety disorder, and social phobia.
The strongest relationship was found between hypersensitivity to CO2 and SAD, while generalized
anxiety disorder was also associated with hypersensitivity, and social phobia was not linked at all.
Carbon Dioxide Sensitivity
The role of carbon dioxide has proven to be very important in the understanding of panic disorder.
The suffocation hypothesis states that it is evolutionarily important to respond to the sensation of
smothering with panic attack symptoms such as hyperventilation and an attempt to escape. A highly
sensitive suffocation alarm, which detects and reacts to increases of CO2, can lead to uncued panic
Panic Disorder 149
attacks, putting one at higher risk for panic disorder [39]; for a recent in-depth review of the suffocation
false alarm hypothesis, see [40]. Empirical support for this theory comes from studies using a CO2
challenge (i.e., breathing in a high level of CO2 which creates the sensation of being smothered).
These studies have found that participants with panic disorder report a significant increase in overall
anxiety as well as specific panic symptoms; healthy controls do not report such responses [41]. This
sensitivity appears to be genetic; for example, healthy relatives of adults with PD report higher rates
of anxiety than controls after engaging in the same CO2 challenge [42]., CO2 sensitivity also appears
to be specific to panic disorder, rather than a trait common to those with other related disorders. For
example, one study compared CO2 responses across three groups: those with at least one panic-disor-
dered relative, those with at least two manic and/or depressed relatives (putting them at high risk for
depression or anxiety), and those with no family history of anxiety, mood, or substance disorders [43].
Nearly 50 % of those in the panic group had a panic attack following the challenge, while no panic
attacks occurred in the other groups. As carbon dioxide sensitivity is under opioid control, it has been
suggested that panic disorder may be caused by an endogenous opioid deficit [40]. This theory may
have implications for treating panic disorder through the use of opioid agonists, though this has not
yet been tested in youth.
Assessment
Currently, there are no measures specifically designed to assess panic disorder symptoms in children
and adolescents. Rather, there are measures of general pediatric anxiety that include subscales specific
to panic symptoms as well as adult measures that have been adapted for use with younger populations.
These measures will be discussed here. See Chap. 12 for a discussion of measures used in the broader
assessment of pediatric anxiety disorders.
Panic Disorder Severity Scale
The Panic Disorder Severity Scale (PDSS) is a brief interview measure designed to assess the severity
of panic symptoms and level of impairment of those symptoms [44]. This seven-item assessment
provides a 5-point Likert scale that assesses the following domains: frequency of panic attacks, dis-
tress caused by panic attacks, amount of fear/avoidance related to the attacks, anticipatory anxiety
about the attacks, avoidance of symptoms that mimic attacks, and work and social impairment. The
PDSS has good inter-rater reliability and both convergent and discriminant validity [45]. The interview
has been adapted as a self-report questionnaire [46] with good psychometric properties. One caveat is
that all of the psychometric data available to date, both for the self-report and for the interview,
are based on adult samples. However, the benefit of the interview format is that it can easily be used
with children and adolescents, with only mild word changes to adapt to the child’s developmental
level and with school impairment replacing work impairment. At least one clinical study of panic
disorder treatment in a pediatric population [47] has used the PDSS in this way to good effect.
Multidimensional Anxiety Scale for Children
The Multidimensional Anxiety Scale for Children (MASC) is a 39-item questionnaire normed for use
with children ages 7–19 [48]. Both child-report and parent-report versions are available. The MASC
assesses overall anxiety, as well as four empirically derived domains of common childhood anxiety,
one of which is called “Separation Anxiety/Panic.” This 9-item scale assesses specific fears and wor-
ries that a child with SAD or panic disorder might have, such as “The idea of going away to camp
scares me.” The MASC has demonstrated adequate test-retest reliability and differentiates children
with an anxiety disorder from both those without any psychiatric disorders and those with psychiatric
disorders other than anxiety [49].
Screen for Child Anxiety Related Emotional Disorders
The Screen for Child Anxiety Related Emotional Disorders (SCARED) was developed by Birmaher
and colleagues [50] based on DSM-IV definitions of the most common anxiety disorders in children
and adolescents, including panic disorder. The 13-item panic disorder scale focuses primarily on
physiological arousal (i.e., “When my child gets frightened, his/her heart beats fast.”) The SCARED
is comprised of 41 items on a 3-point Likert scale and has identical but separate versions for child
report and parent report (only substituting you/your child). The SCARED has good internal consis-
tency and reliability [50] and has also been found to have good reliability and validity when used in a
clinical sample [51].
Spence Children’s Anxiety Scale
Like the SCARED, the Spence Children’s Anxiety Scale (SCAS) was developed to assess DSM-IV
specific factors of anxiety [52]. The SCAS is designed for use with children ages 8–12 and uses a
4-point Likert scale. It consists of 44 items, 6 of which are filler items asking about positive attributes
of the child, which do not get factored into the total score or subscales; these items are meant to reduce
the possibility of a negative response bias [52]. In addition to a total anxiety score, the SCAS provides
several subscale scores including a 9-item panic/agoraphobia subscale, which asks questions such as
“All of a sudden I feel really scared for no reason at all” or “I suddenly feel as if I can’t breathe when
there is no reason for this.” The SCAS has demonstrated good internal consistency, retest reliability,
and convergent and discriminant validity [52].
Medical Assessment
The somatic symptoms of panic attacks can be very similar to symptoms with a physiological or
medical basis. Thus, it is essential that children experiencing such attacks be assessed by a physician
to rule out any cardiac, respiratory, and/or neurological conditions that may be causing these symp-
toms. It is also important to rule out adverse effects of medications or illicit drugs, particularly in
adolescents [53, 54]. Alternatively, children and adolescents who present with chest pain and/or other
cardiac symptoms should be evaluated for panic disorder once all medical causes have been ruled out.
A study of noncardiac chest pain in youth found that over half of those youth met criteria for an anxi-
ety disorder, primarily panic disorder [55]. Thus, a thorough medical evaluation should be conducted
before concluding that symptoms result from panic disorder, and a thorough psychiatric assessment is
needed once all medical causes have been eliminated.
Panic Disorder 151
Treatment
As the research into panic disorder in children and adolescence remains in its infancy, there are very
few intervention studies for this population. There are a handful of behavioral intervention trials and
only a few noncontrolled psychopharmacological trials.
Cognitive-Behavioral Treatments
Cognitive-behavioral treatments for panic disorder are similar to those used for other anxiety disorders
with one unique component, interoceptive exposure. During these exposures, the patient engages in
exercises to bring on the sensations of panic (e.g., racing heart, dizziness, hyperventilation) in con-
trolled way. This serves to desensitize patients to these sensations and change their cognitions regarding
their dangerousness. Other elements of CBT for panic disorder include emotion identification, cogni-
tive restructuring, and in vivo exposure (to situations that may be avoided due to panic symptoms).
Psychoeducation about the nature and utility of anxiety as well as the safety of panic attacks is also a
feature of most CBT approaches to panic in order to change common cognitive appraisals of panic
symptoms (e.g., “I am dying” or “panic attacks will damage my heart”) [56]. Earlier treatments for
panic disorder included relaxation training; however, more recent treatments have eschewed the prac-
tice feeling that it can increase rather than decrease panic symptoms. When implemented in the midst
of a panic attack, relaxation exercises often fail, leading the individual to believe that the symptoms are
not panic after all but something more dangerous and uncontrollable (e.g., a heart attack) [57].
Panic Control Treatment (PCT), a cognitive-behavioral intervention developed to treat panic disor-
der in adults [58] has been adapted by several researchers for use with adolescents. One controlled,
multiple baseline study of PCT was conducted by Ollendick [59] as an initial investigation of cognitive-
behavioral treatment of panic disorder with adolescents. Four adolescents were treated with six to nine
sessions of a modified PCT protocol which included psychoeducation, relaxation, cognitive coping
procedures, and in vivo exposure components. Participants were considered to be “recovered” once
they were free of panic attacks for 2 consecutive weeks. It was reported that each of the four partici-
pants achieved recovery by the end of treatment along with reductions in agoraphobic avoidance and
increases in self-efficacy. Treatment gains were maintained at 6-month follow-up. Researchers at the
Center for Anxiety and Related Disorder at Boston University also adapted the PCT protocol for ado-
lescents (PCT-A). The 11-session treatment addresses the cognitive/misinterpretational aspects of panic
as well as hyperventilatory response and conditioned reactions to physical sensations [57]. Two pre-
liminary case studies supported the potential efficacy of this treatment approach as adolescents evi-
denced both substantial reductions in panic attacks and avoidance of agoraphobic situations [57]. This
initial support led to a randomized control trial to evaluate the treatment compared to a self-monitoring
control group in a sample of 26 adolescents diagnosed with panic disorder. Adolescents in the active
treatment condition had significantly greater improvements in clinician-rated panic disorder and self-
reports of anxiety and depression, with gains maintained at 3- and 6-month follow-up assessments [60].
These findings lend support to the potential efficacy of PCT-A for adolescent panic disorder.
Novel Behavioral Treatments: Intensive Treatment Protocol
In an effort to increase the dissemination of PCT-A, a brief, intensive protocol has been developed
to address family requests for more rapid alleviation of the adolescent’s panic symptoms.
Adolescent Panic Control Treatment with In Vivo Exposures (APE) which is described in more detail
in [61] is administered over an 8-day period. Across the first three 2-h sessions, adolescents receive
psychoeducation, create a fear and avoidance hierarchy, and engage in cognitive restructuring, intero-
ceptive exposure, and homework exercises. In vivo exposures are conducted during two 6-h sessions,
and adolescents are encouraged to practice exposure over the weekend on their own. A final 2-h
session serves as a review of treatment progress and planning session for the maintenance of skills
learned during in session and out of session exposures. Additionally, four 30-minutes weekly tele-
phone check-ins are conducted to review the adolescent’s progress and plan for skills practice. Two
case studies in which APE resulted in significant improvement in panic symptoms were reported by
Angelosante et al. [61]. Preliminary data from 12 patients has provided promising findings, with ado-
lescents experiencing significantly fewer panic attacks, as well as decreased avoidance and improve-
ments in academic, social, and family functioning [62].
As stated earlier, while many medication trials exist for the treatment of panic in adults, no such ran-
domized trials exist for pediatric populations. However, there is some evidence that psychopharma-
cologic treatments for children with panic disorder can be effective. Lepola and colleagues [63]
provided anecdotal evidence from 3 children (ages 9–16) with panic disorder and school refusal
behavior treated with citalopram. They found that the treatment was both safe and effective for these
youth; at the end of treatment, they no longer exhibited panic attacks. Other anecdotal evidence was
provided by Fairbanks and colleagues [64] who as part of an open trial of fluoxetine (40–60 mg) for
youth with anxiety disorders, reported on five youth (ages 10–16) with panic disorder as part of their
diagnostic profile. All five were rated much improved or improved by the end of the trial (6–8 weeks
in length), though four of the five still met diagnostic criteria for panic disorder at that time. A pilot
study by Renaud and colleagues [47] of 12 youths with a primary diagnosis of panic disorder also
assessed the use of selective serotonin reuptake inhibitors (SSRIs) in this population. This sample
consisted predominantly of adolescents, with 11 participants ranging in age from 14 to 17 years of
age and one 7-year-old participant. After a 6–8 week trial, participants were followed for 6 months;
at that time, 75 % of the sample was rated as much improved or very much improved, and 8 of the 12
no longer met criteria for a diagnosis. Fluoxetine was primarily used, though if participants had a
previous negative experience with that medication, another one was tried such that one participant
was given sertraline and two were given paroxetine, instead. Finally, Masi and colleagues [65] con-
ducted a chart review of 18 youths (ages 7–16) diagnosed with panic disorder who were treated with
paroxetine. At the end of treatment (which lasted 2–24 months), 15 of the 18 were rated as much or
very much improved.
Joey’s Story: Treatment and Outcome
Joey’s parents brought him to a psychiatrist after he quit the soccer team mid-season and his first-
quarter report card indicated that he failed gym due to lack of preparedness and participation. The
psychiatrist recommended cognitive-behavioral therapy. The therapist started by explaining the CBT
model of anxiety and providing extensive psychoeducation about the nature of panic attacks. Treatment
then focused on somatic responses to anxiety in order to demystify those symptoms, thereby making
them less anxiety producing. Joey responded very positively to these early interventions. He then
began interoceptive exposures. Joey found the exercises that caused his heart to race or him to feel
overheated to be the most useful. Finally, with his therapist’s guidance, Joey began gradually engaging
Panic Disorder 153
in behaviors he had been avoiding, such as working out, sitting in the middle of the row at the movies,
or going out with friends while leaving his water bottle and his cell phone at home. Treatment took
approximately 12 weeks, and both Joey and his parents were very pleased with his progress.
Summary
Panic disorder with or without agoraphobia is a disorder characterized by recurrent panic attacks,
some of which occur without apparent warning or trigger, and ongoing worry about future attacks.
Research in panic disorder in children and adolescence is still in its infancy and, as such, a great deal
of research is needed in almost all areas. Much of the research around risk factors for panic disorder
have focused on the purported link with early SAD; as the evidence regarding this link is far from
definitive, additional prospective research within the SAD population is needed. Furthermore, greater
research into other risk factors for the development of panic disorder is needed. There is also a relative
lack of research in the treatment of pediatric panic disorder; additional studies are necessary to estab-
lish a gold standard of treatment in this age group and to elucidate what factors may influence treat-
ment response. Larger studies of either traditional or intensive cognitive-behavioral interventions are
needed to establish CBT as an efficacious treatment as per the standards set by the American
Psychological Association [66]. Moreover, there have been no controlled trials of psychopharmaco-
logical treatments in this age group, so such investigations are sorely needed.
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Obsessive-Compulsive Disorder in Children
and Adolescents
Adam B. Lewin, Jennifer M. Park, and Eric A. Storch
Abstract Pediatric obsessive-compulsive disorder (OCD) is a chronic and debilitating neuropsychiatric

disorder that is associated with significant psychosocial and functional impairment. This chapter
reviews the literature on pediatric OCD, including clinical characteristics and etiological theories.
Assessment methods, available treatment modalities (psychopharmacological and behavioral
approaches), methods of treatment augmentation, and directions for future research regarding treatment
dissemination are discussed.
Keywords Obsessive-compulsive disorder • OCD • Children • Adolescents • Treatment • Assessment

• Phenomenology
Case Scenario
Zoe, an 11-year-old girl, was evaluated at an outpatient child psychiatric clinic specializing in obsessive-
compulsive disorder (OCD) on her parents’ referral. She said that following a salmonella outbreak at
her aunt’s farm, everything associated with the farm was now “contaminated.” Because her father
was at the farm at the time of the outbreak, her father and all of her father’s possessions were
contaminated (including pictures of her aunt’s family/farm). Later, she had to wash her hands repeat-
edly throughout the day after touching any person or object that she believed was “contaminated.”
She also took 60–90-min showers each day. Zoe stated that the level of contamination could increase
if two already contaminated objects (or people) were to touch. If she imagined the farm, she would
say a “cleansing” prayer ten times in her head. By the time that she was seen in the clinic, she had
not touched her father in 3 months and refused to enter any room in the house that he may enter,
eat from dishes, or sit in furniture he may have used. Her hands and arms were raw and chapped
A.B. Lewin (*)

Neuropsychiatry – University of South Florida, 880 6th Street South, Suite 460, Rothman Center - Box 7523,
Child Rehabilitation and Development Building, St. Petersburg, FL 33701, USA
e-mail: alewinhealth@usf.edu
J.M. Park
Department of Psychology, University of South Florida, 4202 E. Fowler Avenue, PCD4118G, Tampa, FL 33620, USA
E.A. Storch
University of South Florida, 880 6th Street South, Suite 460, Rothman Center - Box 7523,
Child Rehabilitation and Development Building, St. Petersburg, FL 33701, USA
158 A.B. Lewin et al.
from the repeated washing. Her parents related that she was unable to maintain her friendships
because of these behaviors and that her grades in school suffered due to her symptoms as well.
She acknowledged that she was probably “not really going to get sick” but was too afraid to “risk it”
by not ritualizing.
OCD is a chronic and disabling neuropsychiatric disorder that is characterized by the presence of
intrusive and distress-provoking thoughts or images (obsessions) and/or repetitive or ritualistic behaviors
or mental acts (compulsions) [1]. Pediatric OCD is often associated with significant psychosocial and
functional impairment [2–4]. Youth with OCD endorse high rates of academic difficulties, such as
concentrating on and completing homework, as well as increased rates of family dysfunction [2, 3, 5].
Relative to their unaffected peers, youth with OCD are prone to increased victimization and are less
likely to participate in social activities [4, 5]. These impairments, coupled with symptom severity and
the presence of comorbid disorders, contribute to an all-encompassing diminished quality of life [6].
When left inadequately treated, OCD often follows a debilitating trajectory, where early OCD-related
impairments contribute to later psychological difficulties, such as an increased presence of comorbid
psychiatric disorders [7, 8]. Given these concerns, it is not surprising that OCD is one of the top ten
leading causes of adult disability in the developed world [9].
According to the DSM-IV, an OCD diagnosis requires the presence of obsessions or compulsions
that are distressing, impairing, and/or time-consuming [1]. The symptom profile of OCD is heteroge-
neous; symptoms appear in various themes (e.g., contamination, aggressive, sexual, religious), which
can fluctuate and change over time [7, 10]. It is not uncommon for symptoms to exacerbate during
times of significant stress or change, such as moving to a new location, changing schools, or having a
sickness or death in the family [11, 12]. Children and adults with OCD exhibit similar symptom
presentations where the most common obsessions include fear of contamination, fear of harm to self
and/or others, concerns regarding symmetry, fear of offending God, preoccupation with right and
wrong, need for exactness and order, and saving obsessions [13, 14]. Common compulsions include
excessive or ritualized cleaning; checking, arranging, repeating, or counting rituals; hoarding or col-
lecting behaviors; and praying, confessing, or reassurance-seeking [15]. Factor analyses of various
obsessive-compulsive symptoms in both children and adults have produced four- and five-factor
models comprising distinct symptom dimensions: contamination/cleaning, aggressive/checking,
sexual/religious, symmetry/ordering, and hoarding [16]. Symptom dimensions can be suggestive of
illness course and prognosis [17, 18]. For example, a longitudinal study examined 45 individuals with
OCD and found that at the 9-year follow-up, children who initially presented with hoarding symp-
toms as their primary OCD symptom had remission rates of only 10 % compared to a 54 % remission
rate for children with other primary OCD symptoms [10].
Although symptom manifestation in children and adults is similar, some developmental differences
exist. Compared to adults, youth with OCD may present with a general discomfort, or unpleasant feel-
ing, rather than fear/anxiety when rituals cannot be completed. For example, vague or diffuse symptoms
such as the “not just right” phenomenon are common in youth. The “not just right” phenomenon as
defined by the need to engage in specific behaviors/rituals until the child feels better is often described
as preceded by an urge rather than a specific fear/thought/worry. That is, youth who experience the “not
just right” phenomenon often report that their behavior relieves a sense of “incompleteness” and/or
sensory discomfort rather than harm/fear avoidance [19, 20]. Rituals involving family members, espe-
cially parents, are highly prevalent symptoms in youth with OCD. For example, reassurance-seeking,
confessing/apologizing rituals, and family accommodation, which refers to family involvement in
rituals and modifications in routine and functioning due to obsessive-compulsive symptoms, are
Obsessive-Compulsive Disorder in Children and Adolescents 159
commonplace [21, 22]. Another distinguishing feature of pediatric OCD is limited insight. Whereas
an OCD diagnosis for adults requires some recognition of the excessive and unreasonable nature of
the thoughts and behaviors [1], children are exempt from this requirement and commonly present
with diminished insight [23, 24] and may not consider their symptoms to be distressing.
OCD is currently classified as an anxiety disorder in the DSM-IV-TR. However, several substantial
changes have been proposed regarding the classification of OCD in the upcoming DSM-5, with
some suggesting that OCD should be removed from the anxiety disorders category and subsumed
under a new classification of obsessive-compulsive-related disorders (OCRDs), which include body-
dysmorphic disorder (BDD), hypochondriasis, Tourette’s syndrome (TS), trichotillomania (TTM),
eating disorders, addictions, and autism [25]. Others maintain that there are marked differences
between OCD and the majority of these disorders and therefore, OCD should remain categorized as
an anxiety disorder [26].
Proponents of the OCRD classification base their arguments on an etiological model that cite
similarities in symptom presentation, familial rates, comorbidity, brain circuitry, and pharmacother-
apy treatment response as evidence for the combined classification [25]. However, these assertions
may be premature. The John Hopkins OCD Family Study found amongst 80 individuals with OCD to
have the following rates of anxiety disorders in their first-degree relatives: 16.3 % OCD, 25 % specific
phobia, 22.6 % social phobia, 15.6 % GAD, and 12.6 % separation anxiety [27], while the rates of
OCRDs were the following: 1 % TTM, 4 % “any” eating disorders, and 17 % grooming disorder [28].
In regards to comorbidity, OCD and OCRDs have comorbidity rates that occur higher than by chance,
with individual studies reporting rates up to 16 % for hypochondriasis, 15 % for BDD, 13 % for tic
disorders, 9 % for anorexia nervosa, 4 % for bulimia, and 5 % for TTM [28, 29]. However, consider-
ably higher comorbidity rates for anxiety disorders, such as generalized anxiety disorder (GAD) and
social phobia, are consistently found in those with OCD [27]. Due to the increased rates of familial
anxiety disorders and comorbid anxiety disorder in individuals with OCD, the argument that OCD
and OCRDs are related due to family history and comorbidity is difficult to uphold.
Recommendations have also been made to remove hoarding as a subtype of OCD and classify
compulsive hoarding as a separate disorder in the DSM-5 [30]. Phenomenologically, hoarding appears
similar to OCD, as it is characterized by persistent concern of losing items that are sentimental or may
be needed in the future; the acquisition of items and avoidance of discarding items can be character-
ized as compulsions. However, hoarding appears to be distinct from OCD in a number of ways.
Hoarding frequently occurs in the absence of other OCD symptoms and has weaker associations with
OCD-related comorbid disorders, such as anxiety and depression, relative to other OCD subtypes
[31–33]. Most striking, compulsive hoarders often do not respond to standard pharmacological and/
or behavioral treatments that are efficacious for OCD [34–36]. Additionally, the literature has consis-
tently found distinct differences in genetics and the neurobiology of individuals with compulsive
hoarding compared to those with other OCD subtypes [37–39].
OCD has a prevalence of approximately 1–2 % among youth [40, 41]. Initial symptom presentation
is bimodal, typically occurring during prepuberty (early-onset OCD) and in late adolescence/early
adulthood, with a mean age onset between 6 and 11 years old for early-onset OCD [42]. Age of onset
varies by gender with a male preponderance among those with prepubertal onset; by adolescence, the
gender distribution becomes roughly equivalent [43, 44]. Early-onset OCD is associated with high
rates of familial risk for the disorder, while adult onset OCD has shown low rates of familial risk, sug-
gesting that genetic factors may play an important role in the manifestation and development of
symptoms in early-onset OCD [45, 46].
As previously noted, OCD is a chronic disorder; 80 % of adults with OCD report a childhood onset
of the disorder [43]. Moreover, in a meta-analysis of studies examining the long-term course of 521
individuals with childhood-onset OCD, 60 % remained symptomatic at follow-up points ranging
between 1 and 15 years [47].
Comorbidity
Comorbid disorders are the norm rather than the exception in pediatric OCD with up to 75 % of
children diagnosed with a comorbid psychiatric condition [48–50]. Across several studies, high rates
of anxiety disorders (26–70 %), tic disorders, (17–59 %), depressive disorders (10–73 %), disruptive
behavior disorders (10–53 %), and attention deficit hyperactivity disorder (ADHD; 10–50 %) are
reported [48, 51–53]. Indeed, in a large randomized clinical trial, 80 % of those with pediatric OCD
had at least one other psychiatric disorder, with 63 % endorsing at least one internalizing disorder and
27 % endorsing at least one externalizing disorder [54]. The presence of even one comorbid condition
can have a significant negative impact on presentation and outcome; comorbidity is associated with
increased functional and psychosocial impairment, attenuated treatment response (both behavioral
and medication therapy), and increased risk of relapse posttreatment [55–57].
A diagnosis of pediatric OCD requires the presence of time-consuming, interfering, and/or distressing
obsessions and/or compulsions. Although seemingly straightforward, OCD can be difficult to differ-
entiate from other disorders that may present with similar symptom presentations.
GAD is highly comorbid with OCD [58]. A common symptom of GAD is excessive worry that is
often described as intrusive, difficult to control, hard to resist, and extremely distressing. Additionally,
individuals with GAD may compulsively engage in reassurance-seeking or checking behaviors to
alleviate the anxiety caused by the intrusive thoughts. Although symptoms seem to overlap consider-
ably, the main differentiation between GAD and OCD is the content of the worries. Worries associ-
ated with GAD are generally related to normal everyday situations (e.g., finances, making good
impressions, safety of family), while thoughts associated with OCD are often senseless or irrational
(e.g., if I don’t do everything three times, my parents will die) [59, 60].
Tic disorders also commonly co-occur with OCD [15]. Simple tics, such as sniffing and throat
clearing, can be easily distinguished from OCD due to their brief duration and involuntary nature
[61]. Complex motor and phonic tics, however, can be difficult to separate from OCD-related compul-
sions [61, 62]. Individuals with complex tics often report experiencing premonitory urges prior to the
tics [63] and as such are usually aware of when the tics are about to begin. However, tics and compul-
sions may be differentiated based on the function of the behaviors (tics to reduce unpleasant sensa-
tions and compulsions to reduce anxiety). In other words, tic behaviors are often provoked by physical
urges or sensations while OCD-related behaviors occur in response to anxiety, distress, or fear. As a
result, children with tics will often report that resisting these sensations will cause physical discom-
fort, whereas those with OCD may indicate that refraining from compulsions will result in increased
anxiety and/or a feared consequence.
Obsessions and compulsive behaviors are also hallmark traits of individuals with anorexia nervosa.
However, in anorexia nervosa, these thoughts and behaviors are constrained to content regarding
food, diet, exercise, weight, and appearance [64, 65]. Individuals with anorexia have markedly
poor insight, and their behaviors are driven primarily by appearance and weight-oriented goals.
On the other hand, individuals with OCD may suffer from severe weight loss due to their OCD-
related symptoms, but these cases are generally due to fears of eating certain types of food (i.e., “con-
taminated” foods) rather than fears of weight gain or concern regarding personal appearances [66].
Perseverative thoughts, fixated interests, and repetitive behaviors are commonly seen in children
diagnosed with an autism spectrum disorder (ASD) [67, 68]. To determine whether these symptoms
could be attributed to ASD or OCD, gathering information regarding the function of the behaviors is
essential. Obsessive-compulsive behaviors are anxiety driven; the thoughts often cause distress, and
the ritualistic behaviors are performed to avoid or decrease anxiety. In contrast, in ASD, behaviors,
such as preoccupations with specific objects or interests, are considered rewarding. While parents
may describe these interests as “obsessive,” the function of these behaviors is unlikely related to the
relief of anxiety. Similarly, ASD children engage in repetitive behaviors because they find it soothing
or pleasurable [69].
Etiology
Biological
Neurobiological models have primarily implicated abnormalities in the corticothalamic striatal circuitry
(CTSC) in OCD [70–72]. These circuits between the frontal lobe and basal ganglia are involved in
both initiation and engagement of routine behavior, as well as emotional and motivational processes.
These models cite deficits in the basal ganglia’s ability to filter and inhibit cortical inputs [73, 74].
As abnormalities in the PFC can cause disruption in the ability to inhibit behaviors and thoughts,
deficits within the CTSC may explain the presence of obsessions and ritualized behaviors in OCD
[75–77]. Neurobiological models of OCD have been studied via neuropsychological assessment,
structural imaging techniques such as computerized tomography (CT) and structural magnetic reso-
nance imaging (MRI), and functional techniques such as positron emission tomography (PET), single
positron emission computerized tomography (SPECT), and functional magnetic resonance imaging
(fMRI) [72, 78–81]. Additionally, translational ablation studies suggest that lesions in the prefrontal
cortex (PFC) of primates, which includes regions such as the anterior cingulate, have been shown to
cause perseverative interference in behavioral performance [82].
Although the CTSC model of neuropathogenesis of OCD is better researched in adults, preliminary
evidence derived from volumetric studies provides support for the involvement of CSTC in pediatric
OCD. Pediatric OCD patients have shown neuroanatomical differences from healthy controls, such as
decreased globus pallidus volumes and increased gray matter in the anterior cingulate gyrus [72, 83].
Rosenberg and Keshavan [72] also reported elevated volume in the anterior cingulate gyrus amongst
youth with OCD. Gilbert et al. [84] found that drug-naïve pediatric OCD patients have increased
thalamic volume relative to healthy controls. To lend further support for this model, there is evidence
that thalamic volumes decrease after treatment in those with pediatric OCD [84]. Woolley et al. [81]
found that while engaging in an inhibitory control task, youth with OCD showed decreased activa-
tions in the right orbitofrontal cortex, thalamus, and basal ganglia relative to healthy controls.
It is notable that while data across these methodologies is starting to converge, the exact pathogen-
esis of OCD in youth is not completely understood. This is in part due to small sample sizes, lack of
replication across studies, and wide variability of neuropsychological tests administered in the con-
text of functional assessments. Further, specifics of treatment studies that examine cortical and sub-
cortical changes vary considerably with mixed results [74, 84, 85].
The neuroanatomical literature is also supported by complementary findings regarding neuro-
chemical function in individuals with OCD. Neurochemical abnormalities in the serotonergic system
have been cited as possible mediators of obsessive-compulsive symptom expression [74, 84, 86].
The strongest support for this theory is based on the efficacy of selective serotonin reuptake inhibitors
(SSRIs) and clomipramine in OCD treatment. Amongst those with OCD, SSRIs and clomipramine
have been found to modulate serotonin neurotransmission within the frontal cortex and thalamocorti-
cal circuits as well as decrease orbitofrontal glucose metabolism and thalamic volumes [84, 86].
Abnormalities within the glutamate and dopaminergic systems have also been associated with the
pathophysiology of OCD [87]. Specifically, children and adolescents with OCD have shown not only
reduced glutamate levels in the anterior cingulate [88], but also, glutamate antagonists, such as rilu-
zole, have been shown to be efficacious in reducing OCD symptoms [89]. In regard to dopaminergic
systems, abnormal dopamine-binding patterns in the caudate and putamen have been identified in
adults with OCD [88, 90, 91]. Additionally, atypical antipsychotics have been successful in reducing
OCD symptoms in treatment-resistant adults [92].
Cognitive Behavioral
Behavioral perspectives regarding the etiology and maintenance of OCD are based on a two-factor
model where the fears are first acquired through classical conditioning (an aversive association is
made with an otherwise neutral stimulus) [93, 94] and maintained through operant conditioning (neg-
ative reinforcement) [95]. Exposure to the feared stimuli (physical objects and/or distressful thoughts)
causes an increase in anxiety or distress, and the rituals/behaviors serve to prevent or neutralize the
negative emotions thus maintaining the ritual via negative reinforcement. Likewise, because the asso-
ciation between the neutral stimulus and the perceived feared consequence is preserved, extinction of
the classically conditioned fear is not achieved. Faulty cognitions, such as intrusive thoughts, inflated
sense of responsibility, distorted interpretations, and pathological doubt, are highlighted in cognitive
models of OCD [96]. These faulty cognitions exacerbate the initial distressing worries and propel the
compulsive and/or avoidance behaviors [96, 97]. Cognitive models may have reduced relevance in
the treatment of pediatric OCD given poor insight [23, 24]; thus, behavioral (exposure-based) models
are emphasized [98].
Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcus
Coined by Swedo et al. [99], PANDAS refers to the acute onset and progression of neuropsychiatric
symptoms, including obsessions/compulsions and tics putatively resulting from an autoimmune
response following exposure to the Group A b (beta)-hemolytic streptococcus (GAS). Inflammation
of the basal ganglia, caused by the GAS autoimmune response, is hypothesized to mediate PANDAS-
related OCD symptoms and associated neurological abnormalities [100–102] in a mechanism similar
to the pathophysiology of rheumatic fever and Sydenham’s chorea. Putative diagnosis of PANDAS-
onset OCD requires prepubertal, abrupt onset of OCD (and/or tic) symptoms, episodic or sawtooth
progression and severity of symptoms, temporal association with GAS, and neurological abnormali-
ties (e.g., choreiform movements, hyperactivity, abnormal movements). Not uncommon are reports of
emotional lability, sudden deterioration of motor functioning, neurocognitive abnormalities, stutter-
ing, and enuresis. Like other psychiatric diagnoses, there are no laboratory tests for PANDAS, and the
diagnosis is made by expert clinician review.
Notably, there has been some debate regarding the impact of infection-mediated immunoresponse
on the pathogenesis of neuropsychiatric symptoms such as OCD and tics. Although more empirical
studies are needed, Murphy et al. provide a comprehensive review, including debate within this
emerging area [100].
Assessment
Various factors may complicate the presentation of OCD in children and adolescents. It is not uncom-
mon for children to be secretive and unwilling to report embarrassing thoughts or compulsions [103].
Some children (particularly younger children) may be unable to verbalize their obsessions or be aware
of the link between their cognitions and behaviors. Additionally, parents may be unable to properly
identify OCD symptoms. For example, family members may mistake OCD-related tantrums to be acts
of oppositional behavior, while clinicians can generally differentiate between the two. Given these
factors, as well as the presence of reduced insight, symptom heterogeneity, and comorbidity, a multi-
method and multi-informant assessment approach is necessary for an accurate diagnosis [104]. The
following measures are focused on OCD-specific assessments. Broad-based assessment instruments
are covered in Chap. 12.
Clinician-Rated Measures
Assessment and evaluation of obsessive-compulsive symptom severity is essential to monitor and

track treatment progress. The Children’s Yale-Brown Obsessive-Compulsive Scale (CY-BOCS) [105]
is a 10-item, semi-structured, clinician-administered interview. Considered the gold-standard mea-
sure for OCD severity, the interview provides a comprehensive checklist of commonly endorsed
obsessions and compulsions, which are rated individually based on frequency, distress, efforts to
resist, perceived control, and interference. Ratings are then combined to provide a composite severity
score.
As family accommodation occurs frequently in pediatric OCD, it is important to measure the pres-
ence, frequency, and severity of the accommodating behaviors. The Family Accommodation Scale
(FAS) [106] is a brief clinician-rated measure that provides a composite score that is reflective of the
degree to which family members have accommodated their child’s behavior over the past month.
Parent- and Self-report Measures
Parent- and self-report measures are time- and cost-efficient methods that can supplement clinician
assessment. They are easy to score and interpret and can be used to obtain specific, detailed informa-
tion regarding the nature of the child’s obsessive-compulsive symptoms and associated impairment.
For identifying specific OCD symptom types that the individual may display (i.e., ascertaining specific
OCD obsessions and compulsions the child may have), the Obsessive Compulsive Inventory-Child
Version (OCI-CV) [107] and the Children’s Florida Obsessive Compulsive Inventory (CFOCI) [13]
may be appropriate tools. The CFOCI also assesses OCD symptom severity. The OCI-CV total score
and subscale scores have demonstrated strong internal consistency, test-retest reliability, and treat-
ment sensitivity [107]. The CFOCI has shown good construct and discriminant validity, as well as
acceptable internal consistency [13]. To measure OCD functional impairment (e.g., impairment in
school, home, family), the Child OCD Impact Scale-Revised, Parent and Child Reports, (COIS-RP,
COIS-RC) [3] can be utilized. The COIS-RP and COIS-RC have demonstrated good internal consis-
tency, test-retest reliability, and concurrent validity. For a self-report assay of OCD symptom severity,
the Children’s Obsessional Compulsive Inventory (ChOCI) can be administered [108]. The ChOCI
has shown good internal consistency and criterion and convergent validity [108]. Notably, to obtain a
comprehensive OCD assessment, it is recommended to include an assessment of symptom types,
severity, and impairment, which requires the administration of multiple measures.
Treatment
Currently there are two well-established treatment modalities for pediatric OCD: pharmacotherapy
using SSRIs and cognitive behavioral therapy (CBT) with exposure and response prevention (E/RP).
Both treatment methods, as well as their combination, have demonstrated efficacy in a number of
methodically sound research trials [54, 109–119]. Studies looking at direct comparisons between
SSRIs and CBT have found that CBT monotherapy and combination CBT + SSRI are superior to
SSRI monotherapy [54, 116]. Indeed, practice parameters suggest that CBT alone should be used as
a first-line treatment for mild to moderate cases and combination CBT + SSRI for severe cases [98].
Pharmacotherapy
There are four medications that carry Federal Drug Administration (FDA) indications for use in
pediatric OCD (see Table 1). Clomipramine, a tricyclic antidepressant, is approved for those 10 years
old and older (dosages from 50–200 mg). Table 1 provides the ages and dose ranges for the three
SSRIs approved for use for pediatric OCD (sertraline, fluoxetine, fluvoxamine). To date, citalopram
and escitalopram are not FDA approved for pediatric OCD.
All four medications have produced modest but positive results for the treatment of pediatric OCD.
Clomipramine, once considered the frontline pharmacological approach for OCD, has demonstrated
treatment efficacy in a number of randomized-controlled trials in adults and youth. A recent meta-
analysis summarizing these studies indicated that clomipramine was superior to SSRIs in the reduc-
tion of obsessive-compulsive symptoms in children [120]; nevertheless, clomipramine is not
considered a first choice pharmacotherapy due to the side effect profile and risks associated with clo-
mipramine, such as anticholinergic, anti-adrenergic, and anti-histaminergic responses (e.g., dry
mouth, constipation, dizziness, sweating) [98, 117], as well as medical monitoring of heart rate and
blood pressure irregularities [109]. Recent practice parameters for the treatment of childhood OCD
published by the American Academy of Child and Adolescent Psychiatry (AACAP) outline baseline
evaluation (including general pediatric examination and system review and assessment of personal
and family history), precautions, and contraindications associated with the use of clomipramine
in children [98]. Please refer to the practice parameters for specific recommendations concerning
clomipramine and other SRIs. Due to these concerns, clomipramine should be prescribed with cau-
tion. See Table 1 for randomized-controlled trials of clomipramine.
More recently, the utilization of SSRIs for pediatric OCD has received significant attention. Fluoxetine
is the most studied SSRI for pediatric OCD and has been tested in three positive randomized-controlled
Table 1 Controlled pharmacotherapy trials for FDA-approved medications for pediatric obsessive-compulsive disorder
Medication FDA-approved ages Studies Dose ranges Treatment response ratesa
Fluoxetine 7 years and up Liebowitz et al. [114] 20–80 mg/day 55–57 %
Geller et al. [111]
Fluvoxamine 8 years and up Riddle et al. [115] 50–200 mg 42 %
Sertraline 6 years and up POTS [54] 25–200 mg 42–53 %
March et al. [121]
Clomipramine 10 years and up DeVeaugh-Geiss et al. [118] 50–200 mg 60–75 %
Flament et al. [117]
a
Response rates based off of multiple outcomes (e.g., CY-BOCS, Clinical Global Impressions-Severity)
trials. In a 13-week, double-blind, placebo-controlled trial (n = 103; ages 7–17 years), Geller et al. [111]
found that fluoxetine demonstrated superior efficacy in reducing obsessive-compulsive symptoms relative
to placebo with 49 % of the fluoxetine group and 25 % of the placebo group deemed treatment respond-
ers. Similarly, Liebowitz et al. [114] conducted a 16-week, placebo-controlled trial (n = 43; ages
6–18 years) and found significantly reduced obsessive-compulsive symptoms for those who received
fluoxetine as opposed to placebo; 57 % of the fluoxetine group was considered treatment responders
relative to 27 % of the placebo group. Fluvoxamine was demonstrated superior to placebo in a 10-week
randomized, placebo-controlled trial (n = 120, ages 8–17 years), with treatment response rates of 42 %
for fluvoxamine and 26 % for placebo [115].
Finally, research also supports the use of sertraline in the treatment of pediatric OCD. March et al.
[121], in a 12-week, double-blind, placebo-controlled trial (n = 187, ages 6–17 years), found that
sertraline was significantly more efficacious in reducing obsessive-compulsive symptoms relative
to placebo with treatment response rates of 42 % for sertraline and 26 % for placebo. Similarly, a
multicenter, double-blind, placebo-controlled trial (n = 112, ages 7–17 years) found that sertraline
combined with CBT-enhanced treatment outcome was superior in reducing OCD symptoms relative
to sertraline alone [54].
Several SSRIs that have not been FDA approved have also been shown to be efficacious treatments
for pediatric OCD. Geller et al. [122] reported that paroxetine, in a 10-week, double-blind, placebo-
controlled trial (n = 203, ages 7–17 years), significantly reduced obsessive-compulsive symptoms,
relative to the placebo group. Obsessive-compulsive symptoms were also significantly decreased in
an 8-week open-label trial of citalopram (n = 15, ages 6–17 years) [123]. Although paroxetine and
citalopram have shown evidence for reducing symptoms in pediatric OCD, due to the stronger
efficacy and safety data available for sertraline and fluoxetine, some caution use of these non-FDA-
approved drugs.
Across trials, SSRIs were well-tolerated with low rates of discontinuation due to adverse events.
Although generally considered safe, SSRIs have been the focus of attention regarding “behavioral
activation syndrome,” which is the stimulation or increase in suicidal thoughts or behaviors as a side
effect of SSRI initiation or dosage increase [124]. Behavioral activation symptoms can include a
worsening of symptoms, increased hyperactivity, impulsivity, talkativeness, or irritability [125–127].
These symptoms have been shown to occur in approximately 3 % of children and adolescents fol-
lowing initiation or change in SSRI treatment [128]. These concerns have lead to the FDA-mandated
“black box” warning labels to remind physicians and patients to carefully monitor SSRI-related
side effects.
Although SSRIs have been shown to be efficacious in the treatment of pediatric OCD, complete
symptom remission occurs infrequently, and up to 42 % of individuals fail to respond to treatment
[129]. For these children, additional pharmacotherapy interventions may be utilized such as atypical
antipsychotic augmentation of SSRIs. These atypical antipsychotics are prescribed off-label and
largely rely on the modest results shown in adult OCD populations. To date, no controlled pharmaco-
logical studies utilizing atypical antipsychotics in pediatric OCD have been reported; rather, the litera-
ture consists of several case studies and open-label trials. For example, Thomsen [130] conducted an
open-label trial of 1–2 mg of risperidone-augmented SSRIs with medication-resistant adolescents and
young adults (n = 17, ages 15–19 years) and found significant reductions in obsessive-compulsive
symptoms posttreatment. Similarly, Masi et al. [131] found in an open-label study (n = 39, ages
12–18 years) that 5–20 mg of aripiprazole augmentation of SSRIs was successful in reducing obses-
sive-compulsive symptoms in medication-resistant cases, producing a treatment response rate of
59 %. Although the use of atypical antipsychotics in refractory cases seem promising, the lack of sup-
porting efficacy data and the high frequency of associated side effects (e.g., significant weight gain)
[132] suggest that further research in this area is warranted.
Cognitive Behavioral Therapy
CBT for pediatric OCD consists of three main components: psychoeducation, E/RP, and cognitive
training. The first session(s) is focused on psychoeducation and rapport building. Next, a fear hierarchy
is created where the child and parents list anxiety-provoking stimuli and rank them from lowest to
highest degree of fear. Third is the core element of CBT for pediatric OCD, namely, E/RP. During
exposure sessions, children are systematically exposed to the feared stimuli outlined in the fear hier-
archy. Children gradually move from low-anxiety exposures to high-anxiety exposures, all the while
refraining from engagement in compulsions or rituals. Exposure and response prevention is based on
the notion that fear extinction can be facilitated through extended and repeated exposures to feared
stimuli. Once a child consistently habituates (i.e., experiences elevated distress at the beginning of
the exposure and eventually experiences substantial decreases in distress at the end of the exposure),
the therapist moves on to the next feared stimuli on the hierarchy. Generalization is common; even
stimuli initially perceived to be extremely anxiety-provoking are often manageable following mastery
of E/RP with lower-level stimuli during the course of treatment.
During treatment, cognitive strategies may be employed when developmentally appropriate (usually
in older children, adolescents, and sometimes bright younger children). Youth are taught to counter
maladaptive cognitive thoughts via cognitive restructuring and constructive self-talk. Cognitive
restructuring teaches children to challenge the validity of their obsessions by developing alternative
explanations for the thoughts. By doing this, the value/importance placed on the obsessions should
putatively decrease, thereby reducing the distress associated with the thoughts (i.e., shrinking the
meaning associated with a given intrusive thought). For younger children, coping phrases (“I can say
‘NO’ to OCD!”) can be helpful in competing against problematic intrusive thoughts that may emerge
(“My OCD controls me and I can’t do anything about it”). However, therapists should use caution
when employing self-talk and other cognitive techniques, making sure the child is not substituting
self-talk and phrases provided in therapy in the place of their rituals (i.e., ritual replacement).
Treatment for pediatric OCD often occurs within the context of the family, even when a specific
family-based intervention is not implemented. As previously noted, children and adolescents with
OCD frequently involve family members in their obsessive-compulsive symptoms; family members
often aid by enabling avoidance of feared stimuli or facilitating the actual compulsions (e.g., washing
contaminated clothes, providing reassurance). Additionally, children and adolescents are substantially
embedded within the family unit and are therefore subjected to a number of variables outside of their
control (e.g., marital dysfunction, family dynamics) and are dependent on their families for support.
Because of this, individual therapy for pediatric OCD is not indicated without substantial parental
support, and structured family-based interventions have been implemented in a number of CBT
efficacy studies.
Although CBT with E/RP has been identified as an efficacious and advantageous method of treatment,
there are a number of factors that may impede treatment response (for review, see Storch et al. [133]).
Variables that are associated with poor treatment outcome include lack of insight and motivation,
expectancy factors, increased family accommodation, and the presence of comorbid disorders.
Clinically, limited insight poses to be problematic, as oftentimes individuals who are less aware of
their symptoms do not attempt to resist or control their obsessions or behaviors. Indeed, children with
poor insight have been found to have greater impairment, increased OCD symptom severity, family
accommodation, and depressive symptoms [23, 57]. Similarly, treatment expectancy and motivation
have been shown to be strong predictors of treatment outcome. Parent and child’s expectations regarding
treatment are associated with OCD symptom reduction as well as treatment adherence [134].
As previously noted, family accommodation occurs frequently in pediatric OCD [22]. Although
family members participate in rituals (e.g., providing reassurance, opening doors, washing clothes) to
reduce the child’s anxiety or anger, family accommodation is related to increased familial stress and
functional impairment [21]. The presence of comorbid disorders, particularly disruptive disorders,
Table 2 Controlled psychotherapy trials for pediatric obsessive-compulsive disorder

Randomized-controlled
trials Intervention Duration Treatment response ratesa
Barrett et al. [112] CBT with E/RP-based individual family 14 weeks Individual family = group
therapy vs. group family therapy family
Storch et al. [113] Family-based CBT with E/RP intensive Intensive: daily Intensive = weekly
(daily) vs. weekly sessions for 3 weeks
Weekly: 14 weeks
Piacentini et al. [110] Family-based CBT (FCBT) with E/RP vs. 14 weeks—12 FCBT > PRT
psychoeducation plus relaxation (PRT) sessions
POTS [54] CBT with E/RP vs. SSRI vs. combination 12 weeks Combination CBT + SSRI >
CBT + SSRI CBT = SSRI > placebo
Asbahr et al. [119] Group CBT vs. sertraline 12 weeks Group CBT = sertraline
de Haan et al. [116] CBT vs. clomipramine 12 weeks CBT > clomipramine
a
Response based upon multiple outcomes (e.g., CY-BOCS, CGI-Severity, CGI-Improvement)
can lead to attenuated treatment response [56]. Indeed, Storch et al. [57] found that the presence of
comorbid externalizing disorders (ADHD, oppositional defiant disorder, etc.) was related to lower
remission rates.
CBT for pediatric OCD has demonstrated robust treatment response rates with studies showing
that up to 90 % of children and adolescents respond to treatment (See Table 2 for an overview of CBT
efficacy trials). These studies have shown efficacy of CBT in comparison to wait lists as well as other
types of psychotherapy. For example, Piacentini et al. [110] reported in a 14-week, randomized-
controlled study (n = 71, 8–17 years) that family-based CBT was superior in decreasing obsessive-
compulsive symptoms compared to individual psychoeducation/relaxation training [110]. The manual
detailing this treatment is commercially available [135]. Similarly, Barrett et al. [112] compared the
efficacy of individual family-based CBT and group family-based CBT in a 14-week randomized,
wait-list controlled trial (n = 77, ages 7–17 years) and found that both groups produced significant
decreases in obsessive-compulsive symptoms relative to wait-list controls with treatment response
rates of 61 % (individual CBT) and 65 % (group CBT). In a 12-session pilot study of 5- to-8-year-olds
with OCD (n = 42), family CBT was superior to family-based relaxation therapy (for the completer
sample but not the intent-to-treat sample) [136]. Among completers, remission was achieved in 69 %
of youth receiving CBT but only 20 % receiving relaxation therapy.
Few studies have compared efficacy rates between CBT and pharmacotherapy treatment. A recent
meta-analysis of randomized-controlled trials for pediatric OCD identified an effect size of 1.45 for
CBT and 0.48 for pharmacotherapy [137]. The POTS trial (Pediatric OCD Treatment Study) [54], the
largest study of its kind, compared sertraline alone, CBT alone, and combination sertraline and CBT.
Although all three groups showed significant decreases in obsessive-compulsive symptoms relative to
the placebo group, those who received CBT alone and combination CBT and sertraline showed the
greatest reductions in symptoms with effect sizes of 0.96 and 1.4, respectively (note: reductions in
CY-BOCS symptoms did not differ statistically between the CBT alone and sertraline alone groups).
Remission rates were fair with 39 % for CBT alone, 21 % for sertraline alone, and 56.3 % for combi-
nation CBT and sertraline. Notably, there was a group by site interaction, with youth receiving CBT
at the site directing CBT for the trial doing better than youth receiving CBT at the site directing phar-
macotherapy. The POTS II trial followed up the initial study in a sample of SSRI treatment-refractory
patients by comparing SSRI management alone, SSRI management with CBT instructions provided
by a physician, and SSRI management with CBT [138]. When compared to SSRI management alone,
SSRI management with CBT had greater decreases in symptoms than SSRI management with CBT
instructions (effect size of 0.85 and 0.16, respectively). It is important to note, however, that the CBT
instructions condition did not include contact with a therapist trained in CBT for OCD. A limitation
of the POTS II trial is that youth who did not respond to community SSRI treatment were recruited as
opposed to prospectively examining SSRI partial-responders/nonresponders following a study-initiated

course of medication. Consequently, there is likely marked heterogeneity in subjects prior to random-
ization, obfuscating interpretation of the results. In an older study, DeHaan et al. [116] reported a
statistically significant advantage for CBT with an effect size of 1.58 (66 % response rate) for intensive
CBT and 1.45 (50 % response rate) for clomipramine in a 12-week trial with 22 youth ages 8–18.
Based on these few comparative efficacy trials, CBT has emerged as the most-often recommended
initial first-line treatment for youth with mild to moderate OCD [139, 140].
Pediatric Autoimmune Neuropsychiatric Disorders Associated

with Streptococcus
Prophylactics, such as penicillin and azithromycin, have been examined as novel treatment methods
for PANDAS subtype of OCD and/or tic disorder [102, 141, 142]. Garvey et al. [142] found in an
8-month, double-blind, placebo-controlled, crossover study of penicillin that penicillin was not
significantly better at decreasing neuropsychiatric symptom exacerbation relative to the placebo
group. In contrast, Snider et al. [141] reported that in a double-blind, randomized, controlled study of
penicillin and azithromycin (n = 23, ages 5–9), neuropsychiatric symptom exacerbations decreased
significantly for both prophylactics. It is important to note that the use of antibiotic prophylactics for
the treatment of PANDAS-subtype OCD and/or immunoglobulin therapy (IVIG) is an experimental
treatment that should be discussed in consultation with an expert in pediatric psychoneuroimmunology.
No data suggest the benefit of surgical approaches to abate or prevent symptoms (e.g., tonsillectomy/
adenoidectomy). Behavioral treatment for PANDAS-subtype OCD is the same for non-PANDAS
OCD and is the only recommended intervention without specialty consultation [143].
Novel Treatments
To target the sizable minority that remain either unresponsive or relapse following treatment, research
has begun to focus on novel treatment methods. d-Cycloserine (DCS) is an N-methyl-d-aspartate
(NMDA) partial agonist that has been shown to enhance learning and facilitate fear extinction [144–146]
and has been examined as an adjunctive agent to CBT. Storch et al. [147] conducted a double-blind,
placebo-controlled treatment trial (n = 30; ages 8–17 years) in youth with a primary diagnosis with
OCD. Results showed that those who received DCS + CBT had greater improvements at posttreat-
ment relative to those who received placebo + CBT, suggesting that DCS + CBT may enhance fear
extinction in children with OCD. Riluzole, a glutamate antagonist, has been examined as a possible
treatment method for treatment-resistant youth [89]. In a 12-week open-label trial (n = 6; ages
8–16 years), Grant et al. [89] found that 4 out of 6 youth experienced substantial reductions in OCD
symptoms. Notably, no practice decisions should be based on a six-subject open trial.
Storch et al. [113] examined the efficacy of intensive (daily sessions for 3 weeks) vs. weekly (once
per week for 14 weeks) family sessions for the treatment of pediatric OCD (n = 40, ages 7–17 years)
and found no differences between the two groups at posttreatment. Treatment response rates were
robust for both intensive and weekly sessions: 90 % and 65 %, respectively. Unfortunately, limited
access to highly trained providers makes E/RP inaccessible for many youth. Web-camera-based CBT
methods have been investigated as a means for treatment dissemination. In a preliminary study, Storch
et al. [148] found in a randomized, wait-list controlled study (n = 31; ages 7–17 years) that
web-camera-based CBT was superior in decreasing OCD symptoms relative to the wait-list group.
Case Follow-up
Zoe and her family participated in 12 weekly sessions of CBT with E/RP, focusing exposure on her
contamination fears and prevention of her washing rituals. In session, exposures began with Zoe
holding contaminated objects that she rated as producing distress levels of a 4 (on a scale of 0–10).
Once she habituated to these items (provided a distress rating of 0 or 1), increasingly more difficult
exposures were practiced. For example, contaminated items that she habituated to previously were
now placed together to increase the level of contamination. She held these items in her hands and
rubbed them along her arms and legs to enhance her anxiety and increase the difficulty level of the
exposure. During these sessions she was instructed to refrain from washing her hands for the rest of
the day. Between sessions, she was to practice E/RP by going into rooms that her father frequented
(his bedroom, office) and to sit in the rooms until she habituated to her anxiety. After five sessions of
E/RP, Zoe reported that she was ready for exposures that would cause her higher levels of distress
(ratings of 8–10). In session, she practiced exposures by tossing a contaminated ball back and forth
with her father. Once she habituated to the anxiety, she moved on to touching her father’s arm for
several minutes. By the following session, Zoe was able to hug her father with limited distress and
anxiety. By the 12th session, Zoe reported an improved ability to manage her contamination fears and
washing, as well as an overall decrease in anxiety. Her parents reported an increased understanding
on how to react to Zoe’s obsessive-compulsive symptoms and how to refrain from accommodating her
symptoms. Both Zoe and her parents noted understanding on how to intervene in the future should the
obsessive-compulsive symptoms reemerge.
Conclusions
OCD in children and adolescents is an impairing neuropsychiatric syndrome that, if untreated, can
persist into adulthood and contribute to marked disability. Fortunately, efficacious treatments are
available. Exposure and response prevention has emerged as the leading empirically supported behav-
ioral treatment for pediatric OCD. Studies emphasizing these behavioral approaches within a family-
based context appear to have more robust outcomes. Although pharmacotherapy is a more readily
available efficacious treatment method than CBT, remission rates for SSRIs are lower than for CBT
with E/RP, and the potential for adverse events is higher. Additionally, a substantial minority do not
respond to CBT and/or pharmacotherapy. Consequently, current research seeks to better understand
factors that facilitate and expedite treatment, so that increasingly individually targeted and cost-effective
CBT can be disseminated. The field has already begun to examine innovative methods of treatment
dissemination in children and adolescents, such as computer-administered (via web camera) E/RP
[148]. However, further investigation into these novel treatment delivery options is warranted.
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Posttraumatic Stress Disorder in Children
and Adolescents
Damion J. Grasso and Joan Kaufman
Abstract Roughly half of children and adolescents exposed to significant trauma develop PTSD, yet
in many at-risk populations in which trauma exposure is known, PTSD is frequently under diagnosed.
Most reliable identification of PTSD involves assessment of trauma exposure information and symp-
tomatology from multiple informants. Over the past two decades, tremendous strides have been made
in the assessment and behavioral treatment of PTSD in children and adolescents. More work, how-
ever, is needed to determine optimal pharmacological intervention strategies, as well as integrative
treatment approaches that can address the wide range of challenges faced by families of children with
PTSD. This chapter reviews the diagnostic history of PTSD, epidemiological data, state-of-the-art
assessment instruments and techniques, risk factors, evidence-based treatments, and promising prac-
tices and innovations. An illustrative case example is also presented to highlight various aspects and
challenges in the diagnosis and treatment of childhood PTSD.
Keywords Posttraumatic stress disorder • Acute stress disorder • Trauma exposure • Child
maltreatment • Trauma-focused therapy
Case Scenario
Jovan is a 12-year-old boy, whose family has an extensive history with child protective services (CPS)
involving ongoing intimate partner violence (IPV), sexual abuse of Jovan’s half sister, and physical
and emotional abuse of Jovan and his half brothers. In response to the most recent incident, when
Jovan’s stepfather stabbed his mother in the leg with a kitchen knife, CPS referred the children to a
community-based outpatient treatment program. Jovan was assessed for trauma-related problems
using a standard child- and parent-report measure of posttraumatic stress disorder (PTSD), as well
as a more thorough semi-structured diagnostic interview. Jovan reported frequent nightmares about
being chased by his stepfather, difficulty concentrating, feeling like he is on “high alert,” and trying
hard to avoid thinking about the abuse and family violence. The assessment indicated that trauma-
focused clinical interventions would be appropriate. While Jovan’s mother acknowledged some of the
D.J. Grasso
University of Connecticut Health Center, 263 Farmington Avenue, Farmington, CT 06030, USA
J. Kaufman (*)
Yale University School of Medicine, 301 Cedar Street, PO Box 208098, New Haven, CT 06520, USA
e-mail: joan.kaufman@yale.edu
178 D.J. Grasso and J. Kaufman
violence, she minimized its severity and was unaware of the full extent of Jovan and his sibling’s
PTSD symptoms. She was initially resistant to participating in clinical interventions because she was
torn between her alliance and dependence on her husband and her wish to “do right” by her children.
In addition, Jovan’s younger brothers completely denied the violence.
PTSD is one of the few disorders defined in the current DSM-IV [1] with an etiology directly linked
to a specific precipitating event. Physical and sexual abuse, as well as intrafamilial violence, are the
most common traumatic events associated with childhood PTSD [2, 3]. Other common traumas expe-
rienced by children include natural disasters, automobile accidents, witnessing community violence,
or experiencing the sudden and violent death of a loved one. By 16 years of age, most children (i.e.,
67.8 % in a nationally represented survey) have been exposed to at least one traumatic event, although
only a small proportion of traumatized children will develop PTSD [4].
PTSD is a relatively young diagnosis. Diagnostic criteria were not introduced until 1980, with the
publication of the DSM-III [5]. In 1987, in response to new data suggesting that symptoms and dis-
tress were normative after traumatic events [6], minimum duration criteria requiring symptoms be
present for at least 30 days were added to the diagnosis of PTSD [7]. This revision, however, created
a dilemma such that the diagnosis of adjustment disorder was the only possible diagnosis for appre-
ciably impairing symptomatology in the first month after significant traumas [6]. Thus, acute stress
disorder (ASD) was born and included in the DSM-IV [1]. A diagnosis of ASD requires the presenta-
tion of symptoms for a minimum of 2 days and a maximum of 4 weeks posttrauma, upon which a
diagnosis of PTSD would be given. An immediate diagnosis of ASD, however, is not required to meet
criteria for PTSD. A diagnosis of PTSD can be specified as acute onset (symptoms begin less than
3 months after trauma), chronic (symptoms last more than 3 months), or delayed onset (symptoms
emerge 6 months after trauma).
Table 1 contains the DSM-V proposed diagnostic criteria for ASD and PTSD in adults and young
children (American Psychiatric Association, http://www.dsm5.org). It is noted in the following text
where DSM-IV-TR and the DSM-V proposed criteria differ.
Criterion A
In DSM-IV-TR, criterion A is comprised of two parts. Criterion A1 specifies that “The person has
experienced, witnessed, or was confronted with an event or events that involved actual or threatened
death or serious injury, or a threat to the physical integrity of self or others” [1]. In the proposed DSM-
V, criterion A1 is changed to limit the range of experiences that qualify as relevant for the diagnosis of
PTSD. This change also applies to ASD. Second, as noted in the table, the DSM-IV criterion A2, “the
person’s response involved intense fear, helplessness, or horror” (p. 467) [1], was eliminated from the
proposed DSM-V criteria for both ASD and PTSD as it was found to have no clinical utility [8].
Criterion B (Reexperiencing)
DSM-IV defines reexperiencing symptoms as including distressing images or thoughts about the
event, nightmares, dissociative episodes, physiological distress in response to reminders of the event,
Posttraumatic Stress Disorder in Children and Adolescents 179
Table 1 Proposed DSM-V criteria for acute stress disorder and posttraumatic stress disorder
Acute stress disorder Posttraumatic stress disorder
A. The person was exposed to one or more of A. The person was exposed to one or more of the
the following events: death or threatened following events: death or threatened death,
death, actual or threatened serious injury, or actual or threatened serious injury, or actual or
actual or threatened sexual violation in one threatened sexual violation in one or more of the
or more of the following ways: following ways:
(1) Experienced the event(s) him/herself (1) Experienced the event(s) him/herself
(2) Witnessing, in person, the event(s) as they (2) Witnessing, in person, the event(s) as they
occurred to others occurred to others
(3) Learning that the event(s) occurred to a close (3) Learning that the event(s) occurred to a close
relative or close friend. In such cases, the relative or close friend. In such cases, the actual or
actual or threatened death must have been threatened death must have been violent or
violent or accidental accidental
(4) Experiencing repeated or extreme exposure to (4) Experiencing repeated or extreme exposure to
aversive details of the event(s) (e.g., first aversive details of the event(s) (e.g., first
responders collecting body parts; police responders collecting body parts; police officers
officers the event(s) (e.g., first responders repeatedly exposed to details of child abuse). This
collecting body parts; police officers does not apply to exposure through electronic
repeatedly exposed to details of child abuse). media, television, movies or pictures, unless this
This does not apply to exposure through exposure is work-related
electronic media, television, movies or
pictures, unless this exposure is work-related
Note: DSM-IV criterion A2 has no clinical utility Note: DSM-IV criterion A2 has no clinical utility
B. Eight (or more) of the following symptoms B. Intrusive symptoms that are associated with the
are present that were not present prior to traumatic event(s) [that began after the traumatic
the traumatic event or have worsened since event(s)], as evidenced by one or more of the
B1. Intrusion symptoms following:
(1) Spontaneous or cued recurrent, involuntary, (1) Spontaneous or cued recurrent, involuntary, and
and intrusive distressing memories of the intrusive distressing memories of the traumatic
traumatic event(s) event(s). Note: In children, repetitive play may
occur in which themes or aspects of the traumatic
event(s) are expressed
(2) Recurrent distressing dreams in which the (2) Recurrent distressing dreams in which the content
content and/or affect of the dream is related to and/or affect of the dream is related to the
the traumatic event(s) traumatic event. Note: In children, there may be
frightening dreams without recognizable content
(3) Dissociative reactions (e.g., flashbacks) in (3) Dissociative reactions (e.g., flashbacks) in which
which the individual feels or acts as if the the individual feels or acts as if the traumatic event
traumatic event was recurring was recurring. Such reactions may occur on a
continuum, with the most extreme expression
being a complete loss of awareness of present
surroundings. Note: In children, trauma-specific
reenactment may occur in play
(4) Intense or prolonged psychological distress or (4) Intense or prolonged psychological distress or
physiological reactivity at exposure to physiological reactivity at exposure to internal or
internal or external cues that symbolize or external cues that symbolize or resemble an aspect
resemble an aspect of the traumatic event(s) of the traumatic event(s)
B2. Dissociative symptoms
(5) A subjective sense of numbing, detachment (5) Marked physiological reactions to reminders of
from others, or reduced responsiveness to traumatic event(s)
events that would normally elicit an
emotional response
(6) An altered sense of the reality of one’s
surroundings or oneself (e.g., seeing oneself
from another’s perspective, being in a daze,
time slowing
(continued)
Table 1 (continued)
(7) Inability to remember at least one important
aspect of the traumatic event (typically
dissociative amnesia; not due to head injury,
alcohol, or drugs
Note: Reworded to make criterions more applicable
across cultures
B3. Avoidance symptoms
(8) Persistent and effortful avoidance of thoughts,
conversations, or feelings that arouse
recollections of the traumatic event
(9) Persistent and effortful avoidance of
activities, places, or physical reminders that
arouse recollections of the traumatic event
B4. Arousal symptoms
(10) Sleep disturbance (e.g., difficulty falling or
staying asleep)
(11) Hypervigilance
(12) Irritable or aggressive behavior
(13) Exaggerated startle response
(14) Agitation or restlessness
Note: Data suggest that acute posttraumatic reactions
may be varied and need not necessarily include
dissociative or other DSM-IV ASD symptom
clusters. Reorganization and rewording address
this issue
C. The disturbance causes clinically C. Persistent avoidance of stimuli associated with
significant distress or impairment in social, the traumatic event(s) [that began after the
occupational, or other areas of functioning traumatic event(s)], as evidenced by one or more
of the following:
(1) Avoids internal reminders (e.g., thoughts, feelings,
physical sensations) that arouse recollections of
the traumatic event(s)
(2) Avoids external reminders (e.g., people, places,
conversations, activities, objects, situations) that
arouse recollections of the traumatic event(s)
D. Duration of the disturbance (symptoms in D. Negative alterations in cognitions and mood that
criterion B) is 3 days to 1 month after the are associated with the traumatic event(s) [that
traumatic event began or worsened after the traumatic event(s)],
Note: Altered from minimum of 2–3 days to reduce as evidenced by three or more (Note: two or
false positives more in children) of the following:
(1) Inability to remember an important aspect of the
traumatic event(s) (typically dissociative amnesia;
not due to head injury, alcohol, or drugs)
(2) Persistent and exaggerated negative expectations
about one’s self others, or the world (e.g., “I am
bad,” “No one can be trusted,” “ I’ve lost my soul
forever,” “My whole nervous system is perma-
nently ruined,” “The world is completely
dangerous”)
(3) Persistent distorted blame of self or others about
the cause or consequences of the traumatic
event(s)
(4) Pervasive negative emotional state (e.g., fear,
horror, anger, guilt shame)
(continued)
Table 1 (continued)
(5) Markedly diminished interest or participation in
significant activities
(6) Feeling of detachment or estrangement from
others
(7) Persistent inability to experience positive emotion
(e.g., unable to have loving feelings, psychic
numbing)
E. The disturbance is not due to the direct E. Alterations in arousal and reactivity that are
physiological effects of a substance (e.g., associated with the traumatic event(s) [that
medication or alcohol) or a general medical began or worsened after the traumatic event(s)],
condition (e.g., traumatic brain injury, as evidenced by three or more (Note: two or
coma), and the symptoms are not restricted more in children) of the following:
to those of brief psychotic disorder:
(1) Irritable or aggressive behavior
(2) Reckless or self-destructive behavior
(3) Hypervigilance
(4) Exaggerated startle response
(5) Problems with concentration
(6) Sleep disturbance (e.g., difficulty falling or
staying asleep)
F. Duration of the disturbance (symptoms
in criteria B, C, D, and E) is more than
1 month
G. The disturbance causes clinically
significant distress or impairment in social,
occupational, or other areas of functioning
H. The disturbance is not due to the direct physi-
ological effects of a substance (e.g., medication or
alcohol) or a general medical condition (e.g.,
traumatic brain injury, coma)
and in young children, trauma-specific play or reenactment. These largely remain intact in the pro-
posed DSM-V. As noted in Table 1, there are a number of qualifications to the criteria for children in
order to account for developmental differences in the presentation of PTSD symptoms. For example,
recurrent thoughts may be evident in children, not only through verbal report, but also in play themes,
e.g., a child who was sexually abused may play out scenes with sexually explicit material or may
‘hump’ his/her stuffed animal. A child who was physically abused may use toys to depict a parent
character hurting a child character, or may hit and shout at a peer while repeating the same things a
parent said to him when he was abused. Reliving the trauma can also manifest as trauma-specific
reenactment in children, which might emerge, for example, as a sexually abused child initiating sex-
ual advances towards other children or toward an adult. In addition, in children, nightmares need not
specifically relate to the traumatic event to contribute towards the intrusion cluster.
Criterion C (Avoidance)
DSM-IV avoidance symptoms include deliberate efforts to avoid activities, places, or people that
elicit memories of the event and avoidance of thoughts or feelings related to the event, as well as
several numbing symptoms (e.g., detachment, anhedonia). As result of several confirmatory factor
analytic studies [9–11], DSM-V proposes to divide avoidance symptoms into two separate clusters:
one comprised of the avoidance symptoms noted above and one including the numbing symptoms and
newly proposed negative alterations in mood and cognition symptoms (e.g., a child who blames him-
self for not stopping the IPV). For ASD, dissociative symptoms are essentially unchanged in the
proposed DSM-V criteria.
Criterion D (Hyperarousal)
Hyperarousal symptoms include sleep difficulties, irritability, concentration problems, hypervigi-

lance, and exaggerated startle. In DSM-V, aggressive, reckless, and self-destructive behavior symp-
toms are also included in this category. Agitation and restlessness are new symptoms included in this
cluster of symptoms for ASD.
Proposed DSM-V Criteria for Preschool Children
It is only within the past decade that the diagnosis of PTSD has been applied to infants and toddlers.
Scheeringa and colleagues [12–15] have proposed new specific criteria for diagnosing PTSD in pre-
school children. These criteria are comprised of the same four core symptom clusters used to diagnose
PTSD in older children and adults; however, items that require reports of subjective experiences were
eliminated from the alternate criteria for preschoolers (e.g., foreshortened sense of future), and all
remaining items were behaviorally anchored (e.g., feelings of detachment operationalized as socially
withdrawn behavior). In the studies by Scheeringa and colleagues [14] examining the utility of the
DSM-IV PTSD criteria with preschool children, the avoidance/numbing cluster was the set of symp-
toms least frequently endorsed in the very young children. Only 2 % of highly traumatized preschool
children endorsed sufficient DSM-IV PTSD avoidance/numbing symptoms (e.g., three symptoms).
Limiting the number of avoidance symptoms to only one resulted in approximately one-quarter of the
highly traumatized children in their studies meeting diagnostic criteria for PTSD, a rate comparable
to that reported in other traumatized samples of older children. Therefore, only one avoidance symp-
tom is required for the diagnosis of PTSD in preschool children in the proposed DSM-V criteria.
Sheeringa and colleagues also examined a cluster of symptoms assessing loss of previously acquired
skills (e.g., toilet training), new-onset separation anxiety, and new onset of fears unrelated to the
trauma, but these were not retained in the proposed DSM-V PTSD criteria for preschool children
because they did not add to the diagnostic utility. However, Scheeringa and colleagues have suggested
that these symptoms may be useful in dimensional assessment tools of PTSD for purposes of predict-
ing treatment outcome, as they were among the most common symptoms observed in young children
across their studies [12–15].
Prevalence
Results from large epidemiological surveys of psychiatric disorders in children and adolescents indi-
cate that the prevalence of PTSD in the normal population ranges from 0.4 % to 3 % [4, 16]. This
percentage is lower than the 6–8 % of United States adults estimated to have lifetime PTSD [17, 18].
As in the adult literature [17, 19–21], the majority of studies report that PTSD is about two times more
prevalent in girls than boys (e.g., 3.7 % boys and 6.3 % girls in the National Survey of Adolescents)
[3, 22–26]. Some, but not all studies [27], have reported higher rates of PTSD in black [3, 16] and in
Hispanic [3] adolescents compared to white adolescents. This may be a reflection of the greater
tendency for minorities to possess other risk factors associated with PTSD (e.g., violence exposure,
low socioeconomic status) [28].
Estimates of PTSD in certain populations of children are much higher than those in the general
population. In a number of small-scale studies of children receiving child welfare services, 26–67 %
met criteria for PTSD [29–37]. Prevalence estimates of PTSD in youth involved with the juvenile
justice system range from 4.8 % to 48.9 % [38–40]. Rates ranging from 18.4 % to 33.3 % are reported
in psychiatrically hospitalized samples of children [41–43]. In homeless youth, more than 80 % were
found to have been physically or sexually assaulted, and 8.3–17.7 % met criteria for PTSD [44, 45].
These ranges are quite large, particularly for youth involved with the juvenile justice system. Most of
the studies reporting higher rates of PTSD involved evaluators who were familiar with the partici-
pants’ trauma histories prior to assessing PTSD symptoms, employed multiple methods (e.g., self-,
parent, and teacher report and semi-structured interview), and utilized multiple sources (e.g., child,
parent, caseworker, CPS records) to identify trauma exposure and symptoms (see Diagnosis and
Assessment Section below for discussion of how these issues affect the diagnosis of PTSD).
Psychiatric Comorbidity and Differential Diagnosis
Approximately three-quarters of adults with PTSD experience one or more comorbid lifetime diagno-
ses, among which 37–48 % report a lifetime history of major depression [17, 46, 47]. In one-half to
three-quarters of all cases, the onset of PTSD is primary. The risk for major depressive disorder
(MDD) following PTSD is about the same as the risk of MDD following any other anxiety disorder
and 30–40 % more likely in individuals with a history of a preexisting anxiety disorder [47]. Numerous
studies also report increased risk of suicidal ideation in individuals with PTSD [48, 49]. PTSD is also
highly comorbid with alcohol and substance use disorders in adolescents and adults [17, 50–52], In
addition, a large national survey of 4,023 adolescents revealed a positive association between number
of trauma exposures and comorbidity of PTSD with MDD and substance use disorders [52].
The diagnosis of PTSD shares numerous symptoms with multiple other common child psychiatric
diagnoses. Determining the presence of PTSD and potential comorbid diagnoses requires careful
assessment of the developmental timing of the onset of symptoms, the pattern of problem behaviors,
the severity of difficulties across different settings, and the association of problem behaviors with
trauma triggers.
PTSD and MDD have four symptoms in common, including anhedonia, insomnia, irritability, and
concentration disturbance. For the diagnosis of PTSD to be given, there must be at least one intrusion
symptom (e.g., flashbacks, nightmares), a cardinal feature of the disorder. For comorbid MDD to be
diagnosed, beyond symptoms that overlap with the diagnosis of PTSD, there should be at least one
symptom that is uniquely associated with MDD (e.g., depressed mood, suicidality).
Irritability is a very nonspecific symptom associated with many of the major child psychiatric
diagnoses including mania and oppositional defiant disorder (ODD). Most symptoms of ODD involve
some expression of irritability, but for a comorbid ODD diagnosis to be given, there should be evi-
dence of a persistent pattern of defiance (i.e., actively defies or refuses to comply with adults’ requests
or rules). While there is general agreement that irritability is a universal feature of childhood mania,
whether irritability should be characterized as episodic or chronic is highly debated [53]. In PTSD,
irritability is frequently worse when the child is exposed to trauma triggers and less evident in non-
emotionally charged environments. The child may also display an eagerness to please adults, which
would be inconsistent with a comorbid diagnosis of ODD.
Concentration problems are part of the criteria for PTSD, mania and attention deficit hyperactivity
disorder (ADHD). Concentration problems associated with ADHD and mania must have been present
in childhood and exhibit a chronic course that is generally worse in a school setting. The problems are
unlikely related to ADHD or mania if they emerged after the trauma and are worse at home or when
exposed to trauma triggers.
Sleep disturbance is another symptom shared by PTSD and several child diagnoses. While both
PTSD and mania are associated with sleep disturbances, decreased need for sleep is the cardinal fea-
ture of mania, and nightmares and insomnia (e.g., wanting to sleep, but not being able to) are the sine
qua non of PTSD.
In PTSD, dissociative reactions may include hallucinations, which is a primary symptom of psy-
chotic disorders. Visual, auditory, or tactile hallucinations have been reported to occur in 9 % of
maltreated children recruited from juvenile court or pediatric clinics [54], 20 % of child sexual abuse
victims on psychiatric inpatient units [55], and 75–98 % of abused children who meet criteria for a
dissociative disorder [56]. These are characterized by a disruption in functions of memory, con-
sciousness, and perception of self and one’s environment [57]. Differentiating between PTSD, MDD
or bipolar disorder with psychotic features, and a primary psychotic disorder has extremely impor-
tant treatment implications. A number of distinctive features of psychotic-like symptoms in trauma-
tized children facilitate this differential diagnosis. For example, hallucinations in maltreated children
are frequently trauma related (e.g., hearing the perpetrator’s voice), are often nocturnal [58], and
frequently resolve with psychotherapeutic intervention and safety reassurances [56]. In addition, the
presence of hallucinations in traumatized children is not typically associated with other psychotic
symptoms that would suggest schizophrenia or another primary psychotic diagnosis. They are less
likely to be associated with negative symptoms (e.g., withdrawn behavior, blunted affect) or abnor-
mal early development as would be typical in childhood-onset schizophrenia [59]. Hallucinations in
traumatized children tend to be associated with impulsive, aggressive, and self-injurious behavior,
nightmares, and trancelike states and less likely to be associated with evidence of formal thought
disorder [60].
Course
Studies examining the trajectory of PTSD symptoms have identified children and adolescents who
present a persistent, chronic course, as well as those who appear more resilient. One study examined
PTSD symptom course over 3–4 years in 125 German children with partial or full PTSD and who
were part of a larger epidemiological study [61]. About a quarter of the youth in the sample presented
with a chronic course, meeting criteria for PTSD at follow-up, while about half showed symptom
remission, and approximately 4 % had subthreshold symptoms at baseline that worsened [61].
Symptom chronicity was predicted by exposure to new trauma between baseline and follow-up [61].
Another study examined latent class trajectories of PTSD symptoms in 201 children referred to the
Navy’s Family Advocacy Program due to parental sexual or physical abuse or witnessing IPV [62].
Two latent class trajectories were identified: a resilient class and a persistent symptom class com-
prised of older youth who reported exposure to a greater number of trauma experiences [62]. A more
recent study reported similar findings in a sample of 190 children with a history of traumatic injury
[63]. The authors followed these children 6–16 years post-injury and identified three distinct sub-
types: children with low symptoms at both time points (57 %), children with elevated symptoms at
baseline who recovered by follow-up (33 %), and children with persistent symptoms (10 %) [63].
Children in the chronic group were more likely to have had a serious injury, and younger children
tended to be in the recovery group [63].
Etiology and Prognosis
The likelihood of individuals developing PTSD and its prognosis are influenced by four primary
factors: genetic factors, biological factors, the nature of the trauma, and posttrauma factors. [64] Each
are described in turn.
Trauma Characteristics
Beyond inherent factors, trauma factors are among the best replicated predictors of PTSD onset,
severity, and persistence. These factors include unexpectedness [65], chronicity [66, 67], emotional
and physical proximity to traumatic event [68, 69], and when applicable, severity of sexual [70] and
physical assault [71]. Another robust predictor of PTSD is the number of types of traumas experi-
enced. Specifically, research indicates a robust positive linear relationship between PTSD and expo-
sure to multiple types of trauma, which has been coined poly-victimization by Finkelhor and colleagues
[72]. Interestingly, experiencing multiple types of trauma is more predictive of symptom severity than
is repeated exposure to the same trauma [73, 74], which suggests a mechanism that has less to do with
chronicity and more to do with the cumulative burden of experiencing multiple types of trauma.
Further, poly-victimization is associated with less tractable and more treatment resistant PTSD [75],
as well as comorbid MDD and substance use disorders [76].
Posttrauma Factors
Factors in the posttrauma environment contribute most in determining the likelihood of PTSD becom-
ing chronic. The absence of social supports and exposure to ongoing psychosocial adversity are the
most potent predictors of PTSD chronicity [68, 69, 77]. Low parental support and a hostile and coer-
cive parenting style, as perceived by children, is a positive predictor of PTSD severity [78]. Moreover,
the presence of comorbid mood and substance use disorders is associated with worse prognosis and
greater psychosocial impairment [79].
Parents’ responses to their children’s trauma experiences also appear to influence children’s
development of PTSD. In one study, greater parental distress to their children’s accidental injury
positively predicted children’s subsequent development of PTSD [80]. In another study, maternal
posttraumatic stress 6 weeks after their children’s traumatic injury predicted more severe posttrau-
matic stress in children 7 months later [81]. Parent distress has also been found to precede more
severe PTSD in children who have experienced terrorism [82]. In another study, parenting stress
partially mediated the positive relationship between family violence exposure and posttraumatic
stress in young children [83].
Cognitive factors posttrauma also appear to play a role in the development of PTSD. In one study,
distorted cognitions (i.e., appraising reexperiencing symptoms as dangerous) and maladaptive cogni-
tive coping strategies (i.e., avoidance-focused) assessed 2 weeks after an accident predicted greater
PTSD severity 3–6 months later [84]. Others have found higher rates of PTSD in youth who report
higher levels of thought suppression [85, 86] and greater negative self-attributions pertaining to the
trauma [87, 88] immediately following the traumatic event.
Genetic Risk
Genetic risk can be ascertained via family studies, twin studies, and molecular genetic studies, each
with unique contributions and limitations. Family studies have shown that the prevalence of PTSD is
higher in relatives of probands with PTSD than in the relatives of trauma-exposed individuals without
PTSD [89, 90]. Family studies, however, are limited in that they cannot differentiate whether the
familial transmission of PTSD is due to genetic or environmental factors (e.g., adverse impact of liv-
ing with a psychiatrically ill parent). Twin studies have revealed three key findings: (1) a so-called
gene-environment correlation showing that genetic factors account for approximately 20 % of risk of
exposure to assaultive traumatic events, but not non-assaultive negative life events [91, 92]; (2) genetic
factors account for approximately 25–40 % of the variance in predicting onset of PTSD following
trauma, statistically accounting for the influence of genetics on the probability of trauma exposure
[93]; and (3) common genetic influences may contribute to the comorbidity of PTSD with other psy-
chiatric disorders including MDD, generalized anxiety disorder (GAD), panic disorder, and alcohol
and substance use disorders [93].
Unlike twin studies, molecular genetic studies can help to identify specific genetic markers of
PTSD risk. Cornelis, Nugent, Amstadter, and Koenen [94] recently published a review of candidate
gene association studies, identifying a total of 30 associated with the development of PTSD, 18 of
which have focused on genes in the dopaminergic and serotonergic systems. Genes involved in brain
development (e.g., BDNF) and stress reactivity (e.g., FKBP5) have also been implicated in the etiol-
ogy of PTSD [94]. Few studies have replicated these findings; data from existing studies suggest that
genes only account for a small portion of the variance in the development of PTSD. Evolving work in
this area is beginning to examine gene–gene interactions, epigenetic measures, gene-behavior asso-
ciations, and other relevant endophenotypes.
Neurobiological Correlates
Considerable more work has been conducted on the neurobiology of PTSD in adults than in that of
children. Emerging research findings suggest the neural circuits implicated in PTSD are related to the
neural circuits underlying fear conditioning [95–98]. Key brain structures involved in the fear condi-
tioning circuit include the amygdala, hippocampus, anterior cingulate cortex (ACC), and ventrome-
dial prefrontal cortex [99]. Fear-potentiated startle paradigms have been used to examine fear
conditioning in patients with PTSD [100]. In a recent study [101], children with PTSD were found to
have elevated startle reflexes, even after effective trauma-focused treatment, suggesting that abnor-
malities in the fear circuit may persist after symptom recovery.
Several meta-analyses have been published summarizing structural [102] and functional [103]
magnetic resonance imaging (MRI) findings in adult patients with PTSD. These findings show that
when compared to healthy controls, adult patients with PTSD have reduced hippocampal [102, 104,
105] and ACC [102] volumes. Findings of amygdala volumes in patients with PTSD have been mixed
[102, 104], but functional data indicate increased amygdala activation during fear conditioning and
emotion processing tasks in patients with PTSD compared to control participants with potential
trauma exposure but without PTSD [106]. Patients with PTSD were also reported to have hypoactiva-
tion in the dorsal and rostral ACC and ventromedial prefrontal cortex [106].
Some brain findings in children are different from adults and suggest that there may be develop-
mental differences in the neurocircuitry underlying PTSD. In terms of hippocampal findings, children
and adolescents fail to show evidence of hippocampal atrophy in contrast to the findings in adults
[102, 104]. One possibility is that genetic predispositions combined with early trauma and resultant
effects on neural and endocrine activity interact to influence volumetric changes later in life [102].
In a recent fMRI study [107], however, children with PTSD were found to have reduced hippocampal
activation during the retrieval component of a verbal declarative memory task compared to trauma-
exposed children without PTSD. While far fewer studies have examined potential amygdala volume
differences in children with and without PTSD, a meta-analysis [104], indicating a small effect,
reported reduced total amygdala volumes in children with PTSD compared to non-traumatized chil-
dren. Children with PTSD have also been found to have decreased prefrontal cortical volumes [108,
109] and reduced ACC N-acetylaspartate to creatine ratio, a marker of neuronal integrity, a finding
that is also present in adults [110]. No studies to date, however, have examined fear conditioning
circuitry explicitly in juvenile populations.
In addition to these neuroimaging changes, one study reports that children with PTSD have reduced
medial and caudal corpus callosum area [111], and another study shows reduced fractional anisotropy,
a measure of axon integrity, in this region of the corpus callosum [112]. This region contains inter-
hemispheric projections from brain structures involved in circuits that mediate the processing of
emotional stimuli and various memory functions—core disturbances associated with PTSD.
Assessment
Assessment of Trauma Exposure
Prior to assessing PTSD symptoms, an examiner must inventory a child’s history of trauma exposure,
a process that is often complicated by informant discrepancies. Consequently, relying exclusively on
one informant to obtain information about trauma exposure increases the risk of failed detection. In
Jovan’s case discussed at the opening of this chapter, the evaluator obtained discrepant reports of
IPV—with Jovan’s half brothers completely denying these experiences. If the evaluator failed to
incorporate other family members’ accounts of the violence, the children’s violence exposure may
have been missed and PTSD not assessed.
Several reasons underlie informant discrepancies. A child’s denial of trauma exposure may stem
from active avoidance symptoms, a hallmark feature of PTSD, which allows the child to suppress
feelings of shame, guilt, or distress that often accompany child abuse [48]. The denial may also reflect
efforts to stymie CPS from filing an abuse or neglect report against a parent, taking custody of the
child, or delaying family reunification. A parent may likewise underreport her child’s trauma exposure
in an attempt to prevent associated feelings of distress, shame or guilt, or to distance herself from
details that trigger recall of her own traumatic past. A parent who is involved with the child welfare
system may fear attracting unwanted scrutiny from CPS. Many parents of youth involved in juvenile
justice have limited awareness of their children’s trauma experiences, as supervision and monitoring
are often lacking [113]. Additionally, foster or adoptive parents may simply lack critical information
about the traumatic lives of the children that are committed to their care.
Given the limited reliability of the parent and child, a report of past trauma necessitates the exami-
nation of other sources when they exist. In fact, data from a study of 116 children in CPS revealed that
assessors would have failed to detect 40 % of sexually abused children, 30 % of physically abused
children, and 16 % of children who witnessed IPV if they had relied solely on parent and child report
without access to child protective service records [32]. In these cases, PTSD symptoms would not
ordinarily have been surveyed, and the diagnosis of PTSD would have been missed. Child and parent
report did, however, contribute unique information. Of the various types of maltreatment, parents
were most likely to report incidents of IPV and occasionally reported incidents of physical and sexual
abuse that occurred in the past when the family was living in another state that their caseworkers were
unaware of. These data highlight the importance of clinicians obtaining information from multiple
sources (e.g., CPS, children, parents, teachers) when making psychiatric diagnoses and delineating
treatment plans for traumatized children.
As reviewed elsewhere [114, 115] and delineated in Table 2 [116–145], several instruments are
available to survey trauma exposure in children and adolescents. Most of the standard semi-structured
and structured child psychiatric diagnostic interviews include a survey of a variety of criterion A trau-
mas. However, specialized measures are also available. For example, the Traumatic Events Screening
Inventory (TESI) [146] and Violence Exposure Scales (VEX-R) [126] assess a wide variety of child-
hood traumas, and both have caregiver and child-report versions. The Child Trauma Questionnaire
(CTQ) [116] provides an excellent assessment of a range of maltreatment experiences. One of the
most comprehensive self-report instruments to date is the Juvenile Victimization Questionnaire (JVQ)
[118], which surveys a total of 34 specific incidents of child victimization. More detailed measures of
IPV can be obtained with the Revised Conflict Tactics Scale (CTS2) [125] or the Partner Violence
Inventory (PVI) [147], and lastly, reliable methods have also been developed to extract and rate sever-
ity of maltreatment experiences from case records [148] and to integrate trauma data from multiple
informants [149, 150].
Assessment of PTSD Symptoms
Obtaining trauma history information prior to assessing symptomatology in children permits clini-
cians to further query children and adolescents who deny traumatic experiences that have been sub-
stantiated by parent or caseworker report. For example, consider what the evaluator of Jovan’s sister
might have said if she had denied sexual abuse despite the evaluator’s prior knowledge:
You’re doing such a great job. Now I wonder if you can answer some questions about something else your case-
worker told me about. Your caseworker told me about the time your stepfather undressed you and touched your
private sexual body parts when you were 9 years old. I don’t need you to explain that to me, but I wonder if you
can think about when your stepfather touched you while answering the next questions.
This method of questioning allows the child a means to endorse possible PTSD symptoms without
having to detail the traumatic event, which is not something a child is expected to master before
receiving treatment. Furthermore, if children are particularly reticent to talk, a clinician might begin
by asking the more benign hyperarousal items (e.g., sleep difficulties, concentration problems, irrita-
bility), progress to asking about avoidance/numbing/negative mood symptoms, and then query about
the more stress provoking reexperiencing items. The fact that the child initially denied the sexual
abuse experiences is sufficient to warrant positive rating of the avoidance item required for the diag-
nosis of PTSD.
Similar to obtaining trauma exposure information, the assessment of PTSD symptomatology is
also best achieved with the use of data from multiple informants. Children are the best reporters of
cognitive and emotional symptoms [151]. Children are also frequently the best to report nightmares
and sleeping difficulties [152]. In addition, parents and other adults who spend time with the child are
good reporters of externalizing behavior problems such as anger outbursts, concentration problems,
and sexual acting out [151]. If children are living in foster care or with other guardians who do not
know them well, obtaining adjunctive information from birth parents and/or schoolteachers can be
enormously helpful. However, parents and caregivers are notoriously poor at identifying internalizing
(e.g., depression, anxiety) symptoms [151]. In fact, one study found that parent report of their chil-
dren’s traumatic stress was more highly correlated with parents’ self-report of traumatic stress than it
was with their children’s self-reported symptoms [78].
Several reviews have identified a number of valid and reliable DSM-IV-based measures for the
assessment of trauma symptomatology in school-aged children [114, 115, 146]. There is only one
Table 2 Standardized measures to assess trauma exposure, acute stress, and posttraumatic stress disorder in children
Measure Format Age group Cost and contact information
Trauma exposure
Childhood Trauma Questionnaire [116] Self-report 12–18 Cost, psychcorp.com
History of Victimization Form [117] Self-report 7–18 Free, vicky.wolfe@lhsc.on.ca
Juvenile Victimization Questionnaire [118] Self-report 7–18 Free, unh.edu/ccrc/juvenile_
victimization_questionnaire.
html
Lifetime Incidence of Traumatic Events [119] Self-/parent 8+ Cost, sidran.org
report
Traumatic Events Screening Inventory [120] Self-/parent 6–18 Free, ncptsd@ncptsd.org
report or
interview
Abuse and neglect
Checklist for Child Abuse Evaluation [121] Interview 7–18 Cost, parinc.com
Child Abuse and Neglect Interview [122] Interview 7–18 Free, robert.ammerman@
chmcc.org
Sexual abuse
Child Sexual Behavior Inventory [123] Parent report 2–12 Cost, parinc.com
Community violence
Survey of Children’s Exposure to Community Parent report 6–10 Free, jrichter@nih.gov
Violence [124]
Domestic violence
Revised Conflict Tactics Scale [125] Parent report NA Cost, wpspublish.com
Violence Exposure Scales [126] Self-/parent 4–10 Free, fox@umd.edu
report
Acute stress disorder
Acute Stress Checklist for Children [127] Self-report 8–17 Free, nikaphd@mail.med.
upenn.edu
Posttraumatic stress and trauma-related symptomatology
Adolescent Dissociative Experience Survey Self-report 11–18 Shipping, jarmstrong@mizar.
[128] usc.edu
Adolescent Self-Report Trauma Questionnaire Self-report 12–21 Free, smweine@ulc.edu
[129]
Angie/Andy Cartoon Trauma Scales [130] Self-report 6–12 Cost, mhs.com
Child Dissociative Checklist [131] Parent report 5–12 Free, frank.putnam@chmcc.org
Child PTSD Symptom Scale [132] Self-report 8–18 Free, foa@mail.med.upenn.edu
Childhood PTSD Interview (Child and Parent Interview 7–18 Free, kenneth.fletcher@
Versions) [133] umassmed.edu
Children’s PTSD Inventory [134] Interview 7–18 Cost, psychcorp.com
Clinician-Administered PTSD Scale for Interview 7–18 Free, ncptsd@ncptsd.org
Children and Adolescents [135]
Computer-Administered Screen for Traumatic Computer- 10–18 Shipping, dgrasso@psych.udel.
Stress PTSD Reaction Index for DSM-IV administered edu
[136] self-report
Darryl’s Cartoon-Based Measure of Interview 6–10 Free, pg27@drexel.edu
Community-Violence Related PTSD [137]
Feelings and Emotions Experienced During Self-report 7–18 Free, vicky.wolfe@lhsc.on.ca
Sexual Abuse [117]
Levonn’s Cartoon-Based Interview for Interview 6–10 Free, jrichter@nih.com
Assessing Children’s Distress [138]
Parent Report of Posttraumatic Interview 6–18 Cost, sidran.org
Symptoms [119]
(continued)
Table 2 (continued)
Measure Format Age group Cost and contact information
Pediatric Emotional Distress Scale [139] Parent report 2–10 Free, conway.saylor@citadel.
edu
Sexual Abuse Fear Evaluation [140] Self-report 7–18 Free, vicky.wolfe@lhsc.on.ca
Trauma Symptom Checklist for Children [141] Self-/parent 13–16 Cost, parinc.com
report
Trauma Symptom Checklist for Young Children Parent report 3–12 Cost, parinc.com
[142]
UCLA PTSD Reaction Index for DSM-IV Self-/parent 7–18 Free, Hfinley@mednet.ucla.edu
[143] report
Weekly Behavior Report [144] Parent report <7 Free, jcohen1@wpahs.org
When Bad Things Happen Scale [145] Self-report 10–20 Free, kenneth.fletcher@
umassmed.edu
measure that specifically assesses ASD symptomatology, the 29-item Acute Stress Checklist for
Children (ASC-Kids) [127]. This measure has been validated with children aged 8–17 years, is avail-
able in English and Spanish, and has an advantage over other PTSD symptom scales in assessing ASD
since it surveys the full range of dissociative symptoms required for the diagnosis of ASD. There are
multiple well-validated scales to assess PTSD symptomatology. These include the University of
California Posttraumatic Stress Disorder Reaction Index (UCLA PTSD RI) [143], the Clinician-
Administered PTSD Scale for Children and Adolescents (CAPS-CA) [135], the Trauma Symptom
Checklist for Children (TSCC) [153], Levonn’s Cartoon-Based Interview for Assessing Children’s
Distress [138], the Angie/Andy Cartoon Trauma Scales (ACTS) [130], and Darryl, a cartoon-based
measure of community-violence-related PTSD in children and adolescents [137].
The UCLA PTSD RI is probably the most widely used instrument in the field; has parent- and
child-report versions, as well as a nine-item abbreviated version [154]; and has validated clinical
cutoffs suggestive of a probable PTSD diagnosis [155]. A computer-administered version of the
UCLA PTSD RI has been developed by the Delaware Division of Prevention and Behavioral Health
Services [156]. The Computer-Assisted-UCLA PTSD RI (CA-UCLA) is fully self-administered and
utilizes written and spoken prompts. Unlike the paper version, the CA-UCLA specifically refers to the
traumatic event when posing all questions that refer to the trauma. Particular strengths of this measure
include the opportunity for youth to complete the screen in private using a laptop computer and head-
phones, and direct-care workers without assessment experience can more readily assess trauma expo-
sure and PTSD.
The TSCC, Levonn, and ACTS are child self-report measures that were developed to assess a
range of symptoms but are not to specifically diagnose PTSD. The Levonn and ACTS both have car-
toon pictures that provide visual cues to help children understand the questions surveyed.
All of the structured and semi-structured research child diagnostic interviews also include items to
assess PTSD symptomatology [157–160]. These interview schedules are comparably reliable in diag-
nosing PTSD. Given the differential diagnostic issues discussed previously, and the high rates of
comorbidity between PTSD and other child psychiatric diagnoses, there is an advantage to using more
inclusive psychiatric assessment measures when evaluating traumatized children.
Current measures of PTSD for young children (under age 6) are primarily caregiver report forms
with little direct assessment of the child. Of the measures available for young children, the
Posttraumatic Stress Disorder Semi-Structured Interview and Observation Schedule is the most
comprehensive, developmentally appropriate, and well validated [115]. An additional measure for
preschool children that is showing good early psychometric properties is the Preschool-Aged
Psychiatric Assessment (PAPA) [161]. The PAPA is an interviewer-based, structured parental inter-
view for the comprehensive assessment of mental health symptoms in children aged 2 through 5,
which includes PTSD. The Trauma Symptoms Checklist for Young Children is also a good tool for
use with young children. It is a parent-report screening checklist that covers a broad range of symp-
toms, but is not meant as an independent assessment of the diagnosis of PTSD [162]. The Levonn
cartoon interview was originally developed for preschoolers and has been used extensively with
children this age [138].
Bearing in mind the wide range of reasonable assessment options, most critical is the use of stan-
dardized, psychometrically sound measures. Unfortunately, despite well-researched benefits and
guidelines, most child health professionals do not use standardized screens for child mental health
problems [163, 164]. Studies in large outpatient mental health clinics have found that unstructured
interviewing underestimates the prevalence of PTSD in treatment seekers by a factor of two to seven
[165]. A recent study examined diagnoses of PTSD derived from case records of children in a residen-
tial facility and those receiving outpatient treatment and compared the prevalence of PTSD in each of
these groups with PTSD diagnosed via a comprehensive assessment of trauma exposure and PTSD
symptoms [166]. Following a more comprehensive assessment, the authors reported a sixfold increase
in PTSD prevalence in the outpatient agency and a 20-fold increase in PTSD prevalence in the resi-
dential facility [166].
Treatment
Several empirically validated treatments have been developed for children with PTSD. Central to the
efficacy of each of these treatments is the importance of evaluating the child’s current safety and
exposure to ongoing risks, delineating strategies to minimize the impact of secondary stressors, work-
ing to strengthen and support the child’s primary caregivers, and identifying trauma triggers in the
environment that exacerbate clinical symptomatology (e.g., contact with the perpetrator, reminders
around the home). A selection of available treatment strategies is described below.
Trauma-Focused Cognitive Behavioral Therapy
Trauma-Focused Cognitive Behavioral Therapy (TF-CBT) [167] is a 12-to-16-session intervention

designed for children ages 3–18 years to reduce behavioral and emotional problems associated with
child trauma exposure. During the initial phase of treatment, the therapist provides psychoeducation
about trauma exposure and traumatic stress and teaches a variety of stress-reduction skills such as
deep breathing, muscle-tension relaxation, emotion identification and regulation, and cognitive cop-
ing. Caregivers also receive education and guidance on effective parenting skills and behavior man-
agement. The core component of TF-CBT is implemented mid-treatment and involves development
of a trauma narrative. The trauma narrative functions as a means of therapeutic exposure and facili-
tates emotional and cognitive processing of the event. The narrative involves identifying thoughts and
feelings related to the event and correcting distorted beliefs or perceptions. After completion of the
trauma narrative, the therapist helps prepare the child and caregiver to maintain future safety and
healthy coping and initiates treatment termination. A focus on enhancing safety earlier rather than
later in treatment may be indicated for children experiencing ongoing trauma exposure, such as com-
munity or domestic violence [168].
Clinical training on TF-CBT can be pursued via workshops conducted by certified trainers, a treat-
ment manual, and a web-based training available at www.musc.edu/tfcbt. A link to ongoing web-
based consultation is available following completion of the web-based training. Further, a clinical
workbook developed by the Delaware Division of Prevention and Behavioral health Services and
distributed to providers throughout the state has been designed to accompany the TF-CBT manual
(electronic copies available on request) [169].
The efficacy of TF-CBT has been demonstrated in a number of randomized controlled trials and
has been deemed “supported and efficacious” based on current standards [154]. Significantly greater
improvements in PTSD, internalizing symptoms, dissociation, sexualized behavior, and social com-
petence in sexually abused children have been observed in children who received TF-CBT compared
to wait-list controls and child-centered therapies [170–178]. In one such study, 79 % of 89 sexually
abused children (ages 8–14 years) who received TF-CBT no longer met criteria for PTSD posttreat-
ment compared to only 54 % of 91 children who received client-centered therapy [172]. Moreover,
therapeutic effects of TF-CBT are maintained over time [170, 175]. In one study, 41 children (ages
8–15 years) showed significantly greater improvement on a number of symptom measures at 6- and
12-month follow-up compared to 41 children who received nondirective therapy [170]. In a noncon-
trolled study, 100 sexually abused children receiving TF-CBT showed a 48 % reduction in symptoms
from pre- to posttreatment [179], and the 64 children that followed-up 2 years later showed an addi-
tional 26 % reduction in symptoms [175]. Similar positive results were obtained in the treatment of
children and adolescents with PTSD secondary to a single-incident trauma who were provided an
alternate but conceptually similar model of CBT [180].
Deblinger and colleagues have recently established a variant of the standard 16-session treatment
that is reduced to eight sessions. One rationale for this was to accommodate families at risk for drop-
ping out of treatment [181]. The study was conducted with sexually abused children, 4–11 years of
age. While both variants led to significant reductions in PTSD symptoms, children who received 16
versus eight sessions had significantly fewer reexperiencing and avoidance symptoms [181]. Similar
results were found in a recent randomized controlled trial of eight-session TF-CBT for children
exposed to IPV. TF-CBT was found to be superior to a standard, client-centered treatment as evi-
denced by 75 % remission in the TF-CBT group compared to 45 % remission in the comparison group
[182]. The latter study also extends the evidence base on TF-CBT by demonstrating that it can be
effective in reducing symptoms of PTSD secondary to nonsexual trauma, as the majority of efficacy
studies have focused on childhood sexual abuse.
In addition to investigating the efficacy of the eight sessions compared to the 16-session treatment,
Deblinger et al. [181] examined each version with and without inclusion of the trauma-narrative com-
ponent and found noteworthy group differences. First, children in the 16-session and eight-session
trauma-narrative versions showed a significantly greater reduction in abuse-related fear posttreatment
than children in the nonnarrative versions. The authors interpreted these differences as reflecting the
greater focus on habituation of trauma responses in the narrative versions and concluded that the
shortened course of TF-CBT may be sufficient in reducing PTSD symptoms for some children [181].
Second, parents in the longer nonnarrative version reported greater improvements in parenting prac-
tices than those in the trauma-narrative version. Relatedly, children in both nonnarrative versions
showed a greater reduction of externalizing behavior problems [181]. The authors interpreted these
findings as reflecting the greater amount of time spent on parent education and behavior modification
in the nonnarrative versions. This raises the question of whether the standard model could provide
more in the way of managing externalizing behavior problems and parent education. Specifically,
though the standard model touches upon behavior management skills, the nonnarrative course allows
for expansion of topics pertaining to increasing positive parent–child interaction, reinforcing positive
behavior, ignoring less severe behavior problems, being directive, and using consequences effectively
[182]. Further, there is more time to implement exercises and role-play towards increasing parent and
child competencies in these areas.
For children with co-occurring traumatic stress and significant behavior problems, Cohen et al.
[183] suggest incorporating a functional behavioral analysis to determine the function of the behavior
and to focus in on the problems most pertinent to the family. Although working with the parent to
develop a problem list for managing and prioritizing the family’s concerns is not a new concept [184],
the practice is sometimes lost in more directive, evidence-based treatments with preselected standard-
ized measures of symptoms and specific milestones already laid out. A recent study found that the
problem list, or top problems approach, as established with the parent and adolescent yielded
client-driven priorities that were clinically relevant; corresponded to items on the Child Behavior
Checklist and Youth Self-Report; and complemented these standardized measures by adding clini-
cally relevant specificity [185].
There have been remarkable efforts to implement and test TF-CBT within community-based men-
tal health systems. In a community-based benchmarking study, which is a noncontrolled effectiveness
study that compares effect sizes to those achieved in efficacy studies, TF-CBT led to significant reduc-
tions in symptoms of PTSD and internalizing behavior problems in children ages 7–17 years exposed
to a variety of trauma types and referred from child welfare, juvenile justice, crisis services, and other
sources [186]. Bigfoot and Schmidt [187] developed and validated an adaptation of TF-CBT for
American Indians and Alaska Natives, called Honoring Children, Mending the Circle (HC-MC),
which blends traditional native teachings with the model components. Finally, De Arellano et al.
[188] has modified office-based TF-CBT to be delivered as a community-based treatment, in or near
the home, to help underserved populations who face significant barriers to treatment and over-repre-
sent families who drop out. The program is called the Community Outreach Program-Esperanzo
(COPE), with a client base largely comprised of ethnic minorities and rural residents. The case exam-
ple in the current chapter is based on a family that received COPE services.
Cognitive-Behavioral Therapy for Sexually Abused Preschool Children (CBT-SAP), which shares
the main principles of TF-CBT, was designed by Cohen and Mannarino to accommodate younger
children [178]. In a study of 77 sexually abused preschool children randomly assigned to CBT-SAP
or nondirective supportive therapy (NST), children who received CBT-SAP showed significant reduc-
tions on a variety of parent-report measures, whereas children in the comparison group did not show
significant change [178]. A follow-up of 43 of the children from this study revealed that children who
had received CBT-SAP continued to show significant reductions in symptoms over the course of a
year, while the NST group showed less change [177].
More recently, Scheeringa, Weems, Cohen, Amaya-Jackson, and Guthrie [189] adapted TF-CBT
for children ages 3–6 years and tested it in a randomized controlled trial. This 12-session protocol was
designed to implement developmentally appropriate components of TF-CBT including psychoeduca-
tion about PTSD, identification of feelings, coping skills, and exposure to trauma-related reminders
using drawing, imaginal exposure, and in vivo exposures, as well as safety planning [189]. Parents
participated in three conjoint sessions, observed all child sessions on a monitor in another room in
order to simultaneously learn the material, and met with therapists individually. The manual and
assessments used are available online at http://www.infantinstitute.com. The authors found that the
TF-CBT group showed a greater reduction in PTSD symptoms than the wait-list control group post-
treatment and at 6-month follow-up; however, the effects were not significant for symptoms of depres-
sion, separation anxiety, ODD, or ADHD [189]. The wait-list control group ultimately received
treatment and combined with the treatment group, symptoms of depression, separation anxiety, and
ODD showed significant reductions at the 6-month follow-up with large effect sizes.
Prolonged Exposure
Prolonged exposure (PE) [190], which has been highly effective for adult PTSD [191], has been
modified for use with adolescents. PE is a manualized treatment, distinct from TF-CBT, consisting
of nine to twelve sessions each lasting 90 min. Introductory sessions include psychoeducation about
PTSD and treatment rationale. The remainder involves repeated imaginal exposure in-session and
assignment of in vivo exposure to avoided trauma cues during the week. Adolescents (12–18 years)
were randomly assigned to PE or dynamic therapy. Both groups showed decreased symptoms of
PTSD and depression; however, PE resulted in the greatest reduction of symptoms, with approximately
two times as many youth no longer meeting criteria for PTSD posttreatment [192]. In addition,
treatment gains were maintained at 6- and 17-month follow-ups. There is a manual available for
using PE with adolescents [193]. Training in PE is conducted via intensive workshops that are
listed on the Center for the Treatment and Study of Anxiety at the University of Pennsylvania
(http://www.med.upenn.edu/ctsa/workshops_ptsd.html).
Relationship-Based Therapy
Another evidence-based treatment has emerged in recent years specifically for preschool children.
Child–parent psychotherapy (CPP) [194] was developed to address the needs of preschool children
exposed to family violence. It is a 52-week dyadic treatment. CPP integrates modalities derived from
psychodynamic, attachment, trauma, cognitive-behavioral, and social learning theories. The parent–
child relationship is used as a vehicle for improving the child’s emotional, cognitive, and social func-
tioning through a focus on safety, affect regulation, the joint construction of a trauma narrative, and
engagement in developmentally appropriate goals and activities. CPP is based on the following
premises:
(1) The attachment system is the main organizer of children’s responses to danger and safety in the
first years of life;
(2) Early mental health problems should be addressed in the context of the child’s primary attach-
ment relationships;
(3) Child outcomes emerge in the context of transactions between the child and environmental pro-
tective and risk factors;
(4) Interpersonal violence is a traumatic stressor with pathogenic repercussions on its witnesses as
well as its recipients;
(5) The therapeutic relationship is a key mutative factor in early mental health treatment;
(6) Cultural values must be incorporated into treatment [194].
In a randomized controlled trial of CPP, 75 young children (ages 3–5 years) exposed to IPV and
exhibiting parent-reported emotional and behavioral problems were randomly assigned to receive
CPP or case management [195]. Results indicated significant reductions in both child and parent
internalizing and externalizing symptoms posttreatment and at 6-month follow-up compared to stan-
dard treatment in the community [195]. A reanalysis of these data found that children who had four
or more trauma experiences showed significantly greater improvement in PTSD symptoms, as well as
internalizing and externalizing behavior problems, than children with fewer trauma experiences [196].
CPP has also been effective in improving attachment, parent–child relationship problems, and emo-
tional and behavioral problems in children in randomized controlled trials [197, 198], although to
date, it has not been tested with preschool children diagnosed with PTSD.
Group Therapy
Several models of group therapy have been developed for the treatment of PTSD. Most are based on
CBT interventions. Multimodality Trauma Treatment (MMTT) [199] is an 18-week, manualized,
group CBT intervention for children exposed to single event traumas. The treatment includes psycho-
education, exposure through trauma narratives, muscle relaxation, breathing exercises, interpersonal
problem solving for anger control, development of positive self-talk, and relapse prevention.
Evaluation of the treatment resulted in a 57 % reduction in the diagnosis of PTSD posttreatment and
an 86 % reduction at 6-month follow-up. Stein and colleagues [200] studied a shorter 10-session CBT
group therapy for PTSD conducted within the school setting. Posttreatment assessments revealed an
86 % reduction in PTSD symptoms for those in the intervention group. These data suggest that group
treatment can be an effective intervention for PTSD secondary to single event traumas.
There are also several school-based approaches. The structure, consistency, and potential support
available at school make it an attractive place to implement group-based interventions. A recent
review identified 16 studies, nine of which were randomized controlled trials [201]. Most had effect
sizes ranging from medium to large in treating PTSD symptoms. The most rigorous of the studies
were examining the efficacy of Cognitive Behavioral Intervention for Trauma in schools (CBITS)
compared to either wait-list controls or office-based TF-CBT [201]. The latter comparison revealed
a higher completion rate in the CBITS, relative to the TF-CBT condition: 91 % versus 15 %, respec-
tively [202]. The authors attributed these findings to the familiarity and close proximity of schools
to the families of the children [202]. The limitations of a school-based setting, however, prevent a
more individual approach to treating PTSD (e.g., developing a trauma narrative), which may be
necessary for the recovery of children with multiple trauma exposures and a more complex symptom
presentation [201].
Finally, Trauma Affect Regulation: Guidelines for Education and Therapy for Adolescents and Pre-
Adolescents (TARGET-A) is a versatile four to twelve-session group intervention designed to treat
symptoms of posttraumatic stress in youth with substance use disorders and co-occurring trauma
symptoms secondary to interpersonal victimization [203]. Key components include developing self-
and affect-regulation skills, interpersonal problem solving, stress management, and social informa-
tion processing. In a randomized controlled trial, TARGET was equivalent to a trauma-informed
outpatient addiction treatment in reducing posttraumatic stress, depression, generalized anxiety, and
substance use but was superior in sustaining sobriety self-efficacy [204]. TARGET has also been suc-
cessfully implemented and examined in a number of juvenile justice facilities and other youth agen-
cies; however, data are not yet available for report.
Preventative Approaches
The Child and Family Traumatic Stress Intervention (CFTSI) is a secondary prevention program for
trauma-exposed youth, ages 7–17 years, at risk of developing PTSD. CFTSI is a 4-session interven-
tion provided to children and parents with the goal of optimizing social and family support and coping
skills shortly after trauma exposure. Specific objectives are to (1) provide psychoeducation about the
effects of trauma and common trauma symptoms; (2) improve child and parent communication about
feelings, symptoms, behaviors, and in turn, increase parent support of the child; and (3) to facilitate
development of skills to cope with symptoms, including guided imagery, thought stopping, and dis-
traction techniques [205]. In a randomized pilot study, 53 youth were assigned to CFTSI and 53 to a
supportive comparison condition. Children who received CFTSI had fewer full and partial PTSD
diagnoses and greater reduction in posttraumatic stress and generalized anxiety than the comparison
group at the 3-month follow-up [205].
Integrative Approaches
Consistent with the notion that childhood victimization and adversity do not exist in isolation [206],
treatment providers must look beyond the referral problem and consider aspects of the family or com-
munity environment that may be maintaining the problem or compromising effective treatment.
Identifying and conceptualizing the multifarious challenges faced by families inform patient
engagement strategies [207], as well as the treatment approach; however, most manualized treatments
are not designed to accommodate many of the coexisting problems faced by families of victimized
children. For example, parental substance abuse, mental health problems, and IPV are common prob-
lems in families of children involved in child welfare [208, 209] and juvenile justice [210].
There are few interventions that aim to address both childhood PTSD and parent behavior/symp-
toms. Multisystemic Therapy for Child Abuse and Neglect (MST-CAN) is a hybrid of traditional
MST designed for physically abused children and their families. Like traditional MST, treatment is
delivered in multiple contexts including home, school, and community and at rates between two and
five times per week depending on the family’s needs. A comprehensive assessment of strengths and
needs of the child and systems in the family’s social ecology informs treatment planning. MST-CAN
differs from the traditional model in that it involves establishing a safety plan based on a functional
analysis of physical abuse incidents, works primarily with CPS rather than juvenile justice, and incor-
porates a clarification process in which the parent accepts responsibility for the abuse and apologizes
to the child and family [211]. MST-CAN also provides several cognitive-behavioral interventions to
address problems, as needed, including anger management, conflict resolution, and prolonged expo-
sure therapy [212] for parents presenting with PTSD symptoms [211]. A randomized effectiveness
trial of MST-CAN compared to enhanced outpatient treatment demonstrated a greater reduction in
PTSD symptoms and internalizing behavior problems, as well as parent psychiatric distress, neglect-
ful and physically abusive behavior, and significant improvements in social support [211].
MST-CAN has been further adapted to address parental substance abuse by incorporating
Reinforcement-Based Treatment (RBT) [213, 214]. Untreated parental substance abuse has been
associated with more severe childhood PTSD, MDD, substance dependence [215], juvenile delin-
quency [216], as well as longer out-of-home placements for children and reduced likelihood of suc-
cessful family reunification [217]. Addressing both parental substance abuse and child maltreatment
concurrently minimizes the placement of children in out-of-home care, while their parents undergo
substance abuse treatment, which has been standard practice [214]. The feasibility of this model,
referred to as Building Stronger Families (BSF), has been examined in a 4-year implementation study
conducted in Connecticut and yielded a 93 % successful completion rate as indicated by sustained
sobriety, stable mental health, permanent placement of children, and reliable housing [214]. Additional
data have not yet been published.
Other opportunities for integrative treatments include combining trauma-focused treatment for
childhood PTSD with interventions to address children’s exposure to IPV [218]. One published effort
described comparisons among a 10-week group treatment program for children exposed to IPV, a
10-week program offering child and parent group sessions, and a wait-list control group [219]. While
assessment and treatment of child PTSD symptoms was not reported, the child and parent group pro-
gram produced a greater reduction of child externalizing symptoms than the child-only groups and the
wait-list control [219].
Integrative treatments focusing on reducing child PTSD secondary to IPV, as well as parent dis-
tress and/or psychopathology associated with IPV, would be a valuable contribution to child welfare.
In many child welfare samples, the majority of CPS reports are the result of children witnessing IPV
[220], which is sometimes documented as emotional abuse, and in other cases, physical neglect,
depending on the state. In our case example, Jovan’s family may have benefitted from such an inter-
vention. Jovan’s mother had been largely nonparticipatory until mid-treatment, when she became
more aware of the consequences her children suffered because of the abusive partner and her involve-
ment with him. This epiphany was likely the result of the therapist’s outreach, as he had made sev-
eral attempts to connect with the mother, share the trauma narratives, and challenge some of her
distorted cognitions, including that she was the only victim of the IPV and that she could not effec-
tively parent her children without a partner. Sharing the trauma narratives allowed Jovan’s mother to
better understand her children’s feelings and thoughts about the IPV and abuse, whereas the children
did not volunteer this information and she did not have the insight to elicit it. The therapist also
encouraged Jovan’s mother to seek professional help for her depression, which she initiated by the
end of treatment.
Psychopharmacological Intervention
Very few studies have examined the pharmacological treatment of ASD and/or prevention of PTSD,
and there are currently no FDA-approved pharmacological treatments for PTSD in children or adoles-
cents. The available research has recently undergone two reviews [221, 222], highlighting the lack of
randomized controlled studies.
A randomized pilot study in children with severe burns and ASD reported that a 1-week low-dose
treatment of imipramine resulted in remission of symptoms in twice as many children as those in the
placebo group, who received chloral hydrate to assist with sleep [223]. In contrast to adult studies,
two randomized controlled pilot studies examined the use of sertraline to treat childhood PTSD and
found null results [224, 225]. To note, however, two uncontrolled open trials of citalopram reported
significant symptom reduction in children and adolescents with PTSD [226, 227]. Atypical antipsy-
chotics have been used in children with PTSD and profound hyperarousal symptoms [228, 229].
A case series examining the use of quetiapine to treat six adolescent boys in juvenile detention for
6 weeks with doses ranging from 50 to 200 mg/day reported a significant reduction of PTSD symp-
toms as measured by the TSCC posttreatment [230]. A case series of risperidone administered to three
physically abused preschool-age children diagnosed with ASD secondary to serious burns found
significant improvement in symptoms posttreatment [231]. In addition, six sexually abused adoles-
cents with chronic PTSD with associated psychotic features showed symptom improvement after a
course of clozapine [232]. A few studies have examined the effect of antiseizure medication on PTSD
symptoms in children and adolescents. One study reported on a subsample (N = 12) of conduct disor-
dered youth with PTSD who were part of a double-blind, randomized controlled trial in which 71
boys with conduct disorder were assigned to a high or a low dose of divalproex sodium (Depakote),
reporting that youth in the high-dose condition showed a greater reduction in PTSD symptoms [233].
Harmon and colleagues [234] administered clonidine over several weeks to seven preschool-age chil-
dren with PTSD enrolled in a day hospital and found significant improvements in PTSD symptoms.
In an explorative study, Loof et al. [235] administered carbamazepine (Tegretol) to 28 sexually abused
children and adolescents with PTSD and reported that 22 of the youth were asymptomatic at the end
of treatment, with the remaining six showing symptom reduction. A pilot study of children with PTSD
suggests some benefit with propranolol. Using a B-A-B (off-on-off) medication design in a clinical
setting, children exhibited significantly fewer symptoms when receiving medication [236]. Open trial
studies show some efficacy for clonidine and guanfacine in the treatment of PTSD in children and
adolescents [237], but RCTs are needed. In summary, studies of pharmacological treatment for child-
hood PTSD have been fewer in number and reveal mixed data. There are many promising agents that
require more rigorous evaluation. In general, there is a paucity of RCTs, especially in the child and
adolescent literature.
It is evident from these reviews that the extant data do not support the use of selective serotonin
reuptake inhibitors as first-line treatments for PTSD in children and adolescents, and there is limited
evidence that the brief use of antiadrenergic agents, second-generation antipsychotics, and several
mood stabilizers may attenuate PTSD symptoms in youth [221, 222]. However, controlled trials of
these agents in children and adolescents with PTSD are needed. To date, pharmacological treatment
choice is best guided by the comorbid diagnostic profile of the child and ideally used to augment
evidenced-based trauma psychotherapeutic treatments.
Novel pharmacological agents that target neurophysiological processes underlying memory

formation are currently being investigated in preclinical and clinical trials. This work is based on
research indicating that acute glucocorticoid release plays a key role in enhancing emotional memory
consolidation and fear conditioning extinction-based learning [238]. Consolidation of memory
requires glucocorticoid release and beta-adrenergic receptor activity in the basolateral nucleus of the
amygdala (BLNA) [238]. While this mechanism is not fully understood, research suggests that it may
be associated with stimulation of NMDA receptors in the BLNA by increasing calcium conductance
and calcium channel subunit expression [238]. NMDA receptor agonists, particularly d-cycloserine
(DCS), have been shown to facilitate fear conditioning extinction learning when administered just
before extinction trials [239]. This has been demonstrated in exposure-based treatment for several
anxiety disorders [238]. Similarly, yohimbine, which increases noradrenergic activity, has been show
to enhance therapeutic learning during in vivo sessions to treat claustrophobia [240]. Unfortunately,
DCS in conjunction with exposure-based treatment for PTSD has not shown beneficial results [241].
One small-scale RCT compared DCS and placebo and reported that remission of PTSD symptoms
was comparable between groups [242]. Other studies are pending.
Given the previous discussion, there is risk that antidepressants and benzodiazepines, which inhibit
glucocorticoids, and reduce cortisol and noradrenergic activity, may attenuate the therapeutic learning
sought during exposure-based treatment [238]. Indeed, preclinical studies have shown that the
influence of antidepressant and anxiolytic on the amygdala and hippocampus disrupt memory con-
solidation in rodents [238]. To note, a recent review of four trials examining potential benefits of
combined psychotherapy and SSRI treatment, one in which involved children and adolescents, failed
to find evidence that combining the two enhanced treatment outcomes [243]. Future research is needed
to further investigate this potential treatment interference.
Case Follow-Up
Jovan and his sister received a total of 16 sessions of TF-CBT provided in the community. Both chil-
dren showed significant symptom reduction from pre- to posttreatment and no longer met full criteria
for PTSD. Jovan’s mother was initially not engaged in her children’s therapy; however, she became
increasingly engaged as sessions progressed. Both children completed trauma narratives and opted
to share them with their mother. Whereas Jovan’s sister wrote a story about her sexual abuse, Jovan’s
narrative was less conventional and involved a graphical representation of what had happened.
During the conjoint session, Jovan’s mother offered praise and support, and she developed a deep
appreciation of the impact of the family violence on Jovan and his siblings. During the course of treat-
ment, Jovan’s mother separated from her husband. Although she was still communicating with her
ex-husband, Jovan’s mother was more independent, sought her own mental health treatment, and took
steps to further remove herself from the abusive partner. At a 3-month follow-up, the children remained
asymptomatic, and CPS had closed the case.
Summary
Over the past two decades, tremendous strides have been made in the assessment and behavioral treat-
ment of PTSD in children and adolescents. More work is needed to determine optimal pharmacologi-
cal intervention strategies and to devise integrative treatment approaches that can address the range of
challenges experienced by families of children with PTSD.
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Selective Mutism
Courtney P. Keeton
Abstract Selective mutism (SM) is an impairing behavioral disorder of childhood characterized by

persistent failure to speak in specific social situations despite the ability to speak in other situations.
SM typically begins during the preschool years but is usually not identified until the early school
years. The disorder occurs in 0.11–2 % of children and persists for most children if untreated. SM is
most often conceptualized as an anxiety disorder and is considered by many to be an early-onset or
developmental variant of social phobia. The treatment literature is dominated by case reports and a
few controlled studies. The most common treatments are those that are also used for pediatric anxiety,
namely, cognitive, behavioral, and pharmacological interventions. Cognitive and behavioral strate-
gies are recommended as the first-line treatment. Selective serotonin reuptake inhibitors are suggested
in cases of treatment resistance and/or high symptom severity or impairment. It is often necessary to
involve the child’s teacher or other school personnel in the treatment plan.
Keywords Selective mutism • Anxiety • Social phobia • Speech problem • Language problem •
Exposure treatment • SSRI treatment
Case Scenario
Naila is a 5-year-old East Indian girl whose parents sought an evaluation out of concern that Naila
did not speak in preschool or currently in kindergarten. They indicated that Naila has an impressive
vocabulary and expressive language skills that she mostly showcases at home with immediate family.
However, they said she seems “like an entirely different child” when at home compared to school and
other places.
Naila’s parents described her as timid in social situations. At age 3 years, she did not sing along
or dance with same-age children during story times at the local library, “froze” when an unfamiliar
child or adult attempted to engage her in play or conversation, and participated in her soccer lessons
only minimally and with much encouragement from her father. Towards the end of the school year,
when the preschool teacher informed the parents that Naila did not talk or sing in class, they were
surprised that she had not “warmed up” by then. Also, the teacher report was inconsistent with their
observations given that Naila was consistently excited about school, always talked about the other
C.P. Keeton (*)

Department of Psychiatry and Behavioral Sciences, Division of Child and Adolescent Psychiatry,
Johns Hopkins Medical Institution, Baltimore, MD, USA
e-mail: ckeeton@jhmi.edu
210 C.P. Keeton
kids, and recited songs and other things she had learned. In addition, Naila had occasional playdates
with one of the kids in her preschool class and was fully verbal during those visits in her home.
Naila’s lack of speech continued to cause significant impairment through age 5. They noticed, for
example, that Naila’s juice box from her lunch had been untouched on numerous occasions because
she could not insert the straw and was unable to ask someone for assistance. Another time, she had
fallen on the playground and had fractured her arm, but had not reported to a teacher that she was
injured and waited until she got home to tell her parents. At the time of the evaluation, Naila’s mother
had stopped working in order to address Naila’s speech problems.
Selective mutism (SM) is an impairing disorder of early childhood in which children who are capable
of speech withhold it in some situations where speech is expected, such as at school or in social situ-
ations involving unfamiliar people. The lack of speech is disruptive to school functioning or social
communication. Persistence of the disorder must occur for at least one month excluding the first
month of school when lack of speech, high anxiety, and difficult adjustment could be normative. Lack
of speech cannot be due to lack of familiarity with the language and cannot be better accounted for by
a communication disorder, such as withholding speech to avoid stuttering, pervasive developmental
disorder, schizophrenia, or psychosis.
SM was originally described as a deliberate refusal to speak. In 1877, the disorder was termed
aphasia voluntaria emphasizing a voluntary capacity to limit speech. In 1934, the disorder was named
elective mutism, still inferring that children acted volitionally to withhold speech. SM first appeared
in the third edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM) as “elective
mutism.” The term was revised in subsequent versions of the DSM to “selective mutism” to empha-
size that speech is context dependent or selective. It is currently included in the “Other Disorders
of Childhood and Adolescence” diagnostic category; however, SM is being considered as a specifier
for social phobia (SOP) for DSM-5 (www.dsm5.org). In the International Statistical Classification
of Diseases and Related Health Problems (ICD-10) [1], the term “elective mutism” (F94.0) is used
and falls in the category “Disorders of social functioning with onset specific to childhood and ado-
lescence.” The DSM-IV-TR and ICD-10 define similar criteria, but the ICD-10 specifies that the
child must be within two standard deviations on standardized tests of language expression and
comprehension.
Lack of Speech
The hallmark feature of children with SM is a clear discrepancy between a child’s speech abilities and
their speech performance across situations. Most children with SM are like any other child in the home
environment; they speak freely to parents and siblings, laugh, sing, argue, yell, narrate their own play,
and respond to as well as initiate speech. In social contexts such as school and public forums, there is
a marked contrast in speech behavior, and the usually verbose child shows silence or reduced speech
and may show visible distress, reduced affect, and withdrawn behavior [2]. This discrepancy explains
why many parents go months or even years without realizing there is a problem. In extreme instances,
a child has bouts of reducing or withdrawing speech even with parents [3]. Many children with SM
communicate using gestures such as nodding and pointing. Some communicate using short (monosyl-
labic) utterances or speak in an altered voice such as a “baby” voice or making grunts. Others withhold
nonverbal gestures and appear “frozen” with regard to physical presentation and affect [4, 5].
Selective Mutism 211
Variability of Speech
SM is a heterogeneous disorder with variability of speech patterns across and within affected children
[2]. Compared to speech at home, children with SM tend to speak less to familiar individuals in public
and rarely speak to unfamiliar individuals in public or at school [6]. Whereas some children may not
smile, laugh, or participate nonverbally at school, others are creative in communicating and participat-
ing fully in the absence of speech. Some children may be silent in the school context but speak openly
in public, whereas others may reduce speech in most social forums. Likewise, some children may
speak openly to select individuals, including a new clinician, and withhold speech with others, and
there is not necessarily a recognizable explanation or pattern. A child may speak to specific individuals
on some occasions, but not other times. It is not uncommon for a child to enjoy a birthday party including
verbal participation and to withdraw entirely at another birthday party without identifying a reason for
the difference. Thus, there is a generous range of speech behaviors among affected children.
Social Skills Deficits
Compared to typically developed peers, children with SM show lower social competence such as
social assertion, social responsibility, and verbal and nonverbal social skills [7, 8]. Compared to chil-
dren with mixed anxiety, children with SM were rated by observers as lower on verbal social skills
and higher on social anxiety [9]. In another study, children with SM were rated similarly to children
with SOP and scored lower than normal controls with regard to social skills [10].
Impairment
SM is disabling to children’s social, academic, language, and personal/emotional development.

Socially, children with SM tend to withdraw and isolate themselves, which leads to reduced opportu-
nities for friendship formation and extracurricular opportunities, as well as acquisition or mastery of
social skills including pragmatic communication and leadership abilities [6, 8, 11, 12]. Peer rejection
and bullying are also possible because of the SM child’s inability to protest maltreatment by peers [13].
Academically, children with SM are unlikely to participate verbally at school, including answering or
asking questions about content and assignments, and this can interfere with a teacher’s ability to
evaluate achievement [14]. Indeed, school is typically the first setting in which significant functional
impairment is evident, and some children are held back from promotion to the next grade due to fail-
ure to speak in school [15]. Avoidance of social conversation may also lead to language deficits over
time [16]. Affected children may also feel insecure about themselves, leading to decreased autonomy
and self-doubt [3]. Failure to voice a need can result in other functional impairments or personal
humiliation, e.g., the child who does not request a bathroom pass and subsequently has an accident in
the classroom. Overall, SM is a serious condition that can significantly impair the functioning of
young children.
Physiological Findings
Only two studies have been published on the physiological mechanisms of SM. In the first study, 16
individuals aged 5–16 years with SM and matched controls were tested for speech reception thresholds,
212 C.P. Keeton
speech discrimination of phonetically balanced monosyllabic words, and efferent auditory activity
using measures of middle-ear acoustic reflex (MEAR) thresholds, MEAR decay function, and sup-
pression effect of transient evoked otoacoustic emissions [17]. Afferent auditory function was assessed
using auditory brainstem response. As a group, children with SM displayed reductions in auditory
efferent activity; however, 25 % of the group did not display these abnormalities. In a follow-up study,
nine children with SM and abnormal auditory efferent activity showed impaired auditory processing
during a vocalization task [18]. Findings of the two studies provide some evidence that children with
SM who have difficulty processing incoming auditory information while speaking may cope with this
difficulty by resorting to speech avoidance.
Another study has compared psychophysiological arousal in 10 children with SM (aged
7 ± 1.8 years) to 11 children with SOP (aged 8.8 ± 2.0 years) and 14 non-disordered children (aged
8.9 ± 1.5 years) [19]. They compared heart rate, blood pressure, and skin conductance during role play
and read-aloud tasks. There were no differences in heart rate or blood pressure changes across the
three groups. Contrary to the authors’ hypothesis, the SM group, like the control group, showed low
levels of arousal (skin conductance) during the social interaction tasks suggesting a lack of heightened
anxiety or that speech avoidance was used as an emotion regulation tactic keeping arousal low. Given
the small sample size of this study, additional research is needed to draw firm conclusions.
Estimates of SM prevalence vary based on whether the sample is clinical or community based, with
higher rates generally found in community samples. Relatively lower prevalence rates in treatment
settings support the notion that a high percentage of affected children are never seen for treatment
[20]. The prevalence of SM has not been assessed in the majority of existing large-scale epidemio-
logical studies of childhood psychopathology. Studies in primary care and psychiatry clinics esti-
mate the prevalence in these treatment settings at 0.5 % and 0.11 %, respectively [21, 22]. A
community study conducted in the United States estimated a prevalence of 0.71 % in children attend-
ing kindergarten through second grade [14]. Similarly, a study conducted in West Jerusalem using
similar methodology found a prevalence rate of 0.76 % in children ages 4–6 years [23]. A higher rate
of 1.9 % was reported in a study conducted in Finland with 2nd grade teachers [24]. In comparison, a
lower prevalence rate of 0.18 % was found in Sweden; this sample was somewhat older (7–15 years)
and also utilized teacher reports. Another study conducted in the United States using a primary care
sample of children, ages 8–17 years, estimated a rate of 0.5 % for SM [22]. According to Bergman
et al. [14], SM occurs at rates that are comparable to, or greater than, other well-understood childhood
psychiatric disorders such as obsessive-compulsive disorder, autism, major depressive disorder, and
Tourette syndrome.
Age of Onset
Age of onset is typically before age 5. The mean age of onset of SM ranges from 2.7 to 4.1 years
[3, 7, 20, 23, 25]; however, the average age of referral to treatment is 6–9 years of age [26]. The
disorder either may not be discovered until the child enters school, or parents and/or doctors expect
the child to “grow out of it” when signs of the problem are evident during the preschool years [4].
In most cases, onset is insidious, with children being described as having a behaviorally inhibited
temperament throughout their early development [20]. However, there are cases when onset is abrupt,
such as in response to a stressful event [3, 27], and these cases may be transient in relation to those
with a gradual onset [2].
Demographic Distribution
The literature is somewhat inconsistent regarding a gender difference. It is suggested that SM is

slightly more common in females, showing ratios of 1:1.5–1:1.9 for example [3, 20, 25]. Given that
others have documented comparable prevalence among the sexes [14], the suspected gender differ-
ence may result from research limitations such as small sample sizes [28].
Rates of SM appear to be higher in children who have immigrated from one country to another, and
there is a change in native language [23, 29]. For example, one study reported a prevalence rate of
2.2 % for children who had immigrated to West Jerusalem (mostly from other Israeli cities, and for
whom Hebrew was not the primary language) and a rate of 0.47 % in native children. There appear to
be no differences in SM prevalence by socioeconomic status [3, 30] or race [31].
Course
SM does not appear to resolve spontaneously. One community-based case-controlled study found that
27 % of elementary school children with SM showed some improvement at a six-month follow-up but
that the majority remained significantly impaired compared to their unaffected peers [14]. A retro-
spective study of 153 children and adults affected by SM indicated that many continue to suffer from
social anxiety even if SM resolves [2].
Follow-up data of clinically referred and treated individuals suggests that children with SM con-
tinue to experience communication deficits, social withdrawal, anxiety disorders, and psychosocial
impairment into adulthood. One follow-up study of 45 young adults who were diagnosed with SM as
children found that 16 individuals (39 % of sample) showed complete remission, 12 individuals
(29 %) showed remarkable improvement, eight individuals showed mild improvement, and five
showed no improvement [32]. Many individuals in the “remission” group reported other problems
such as mood problems. There is one controlled, long-term outcome study of SM in young adulthood; the
mean follow-up period was 13 years, and there was a remission rate of 58 % [33]. At follow-up, only 18 %
of the sample had slightly improved. In this study, there were high rates of phobic disorders and other
diagnoses at follow-up, even when SM had remitted. In these long-term follow-up studies, high rates
of familial mutism and shyness predicted unfavorable outcomes [32, 33]. In another study, 17 children
(mean age 8 years) were evaluated 6 to 8 months following the initiation of treatment, and all but one
of them continued to meet diagnostic criteria despite significant symptomatic improvement [34].
Comorbidity
SM most commonly co-occurs with anxiety disorders, elimination problems, disruptive behavior, and
communication disorders.
Anxiety
Children with SM score high on measures of social anxiety and shyness [3, 7, 10]. Rates of SOP in
children with SM are high, with comorbidity estimates in some samples of SM up to 97–100 % [6, 9,
20, 35]. Although children with both SOP and SM do not endorse higher levels of anxiety than
children with SOP only, blind observers, clinicians, and parents have rated them as having more
severe symptoms [9, 14, 19, 36]. Other common comorbid anxiety disorders include separation anxi-
214 C.P. Keeton
ety (31.5 %), specific phobia (13 %), and GAD (13 %) [25]. Some studies document high rates of
physical symptoms, which are also consistent with anxiety disorders; children with SM, for example,
scored significantly higher than controls on the somatic subscale of the Screen for Child Anxiety
Related Disorders measure [37], and these results were demonstrated in an earlier study that used the
Revised Ontario Child Health Study scales [7].
Given the high levels of social anxiety in SM, many consider this disorder a relative of SOP. Some
suggest SM is an extreme form of SOP, whereas others consider SM a developmental variant of SOP
[20, 31]. Prior suggestions that SM could be classified as a subtype of SOP [20, 38] and recent recom-
mendations that “refusal to speak” is a behavioral symptom of social avoidance, similar to school
refusal [31], have led the DSM-V Task Force to consider SM as a specifier of SOP rather than main-
taining it as a distinct disorder (www.dsm5.org).
Elimination Disorder
Several studies suggest high rates of toileting problems in children with SM, including constipation,
enuresis, and encopresis. In their sample of 30 children, Black and Uhde [20] reported that 17 % had
enuresis and 7 % had encopresis. Steinhausen and Juzi [3] reported that 33 % of their sample (n = 100)
had enuresis and/or encopresis. Other studies have compared rates of lifetime elimination disorder in
an SM group relative to healthy controls. Kristensen [25] studied 54 children with SM and reported a
rate of 31.5 % of elimination disorder compared to 9.3 % in the control group. In another study of 70
children with SM, rates of enuresis were 14.3 % compared to 6.5 % in the control group, but in this
case the difference was not statistically significant [39].
Disruptive Behavior
Data is mixed with regard to the frequency of disruptive behavior in the SM population. Many studies
describe 10–90 % of children with SM as oppositional, aggressive, or controlling without necessarily
fulfilling diagnostic criteria for a disruptive behavior disorder [3, 6, 20, 40, 41]. Some studies show
no differences in parent-reported or teacher-reported externalizing behaviors such as ADHD, ODD,
and CD among children with SM and healthy controls [7, 14, 37, 42]. In contrast, when compared to
children with SOP, parents of children with SM and SOP reported significantly higher (though in the
nonclinical range) scores on the delinquency and aggression scales [9]. Another study found that 29 %
of children with SM and SOP had comorbid oppositional defiant disorder, in comparison to 5 % of
those with SOP only [43]. Finally, a latent profile analysis of 130 children with SM, ages 5–12 years,
resulted in three distinct groups including an exclusively anxious group, an anxious-communication-
delayed group, and an anxious-mildly oppositional group [41].
Some oppositionality such as arguing or refusing may be explicitly related to an anxiety-provoking
situation rather than generalized disruptive behavior [44]. Children with SM may appear oppositional
in the settings where speech is withheld if they are perceived to be remaining silent as an act of
defiance. However, many children with SM (like anxious children) are cooperative and reluctant to
draw attention to themselves through acts of misbehavior.
Communication Disorders
The DSM specifies that SM should not be diagnosed if the lack of speech is better accounted for by a
communication disorder. Although children with this disorder generally have normal language skills,
there may occasionally be an associated communication disorder (e.g., Phonological Disorder,

Expressive Language Disorder, or Mixed Receptive-Expressive Language Disorder) or a general
medical condition that causes abnormalities of articulation. Many studies show evidence of delayed
speech acquisition or poor articulation in the SM population, and the percentage of language or commu-
nication problems in children with SM varies widely, ranging from 11 % to 65 % [3, 25, 30, 45]. When
compared to children with SOP, children with SM performed worse on nonverbal tests of language [46].
Thus, speech delays and other language problems are not uncommon in the SM population.
Etiology
Views on the etiology of SM have changed over recent decades. Older conceptualizations of SM
implicated factors such as trauma, stressful events, or family dysfunction as etiological variables
[45, 47–50]. Current conceptualizations, which are discussed further here, are based on symptom
overlap with SOP and suggest that multiple variables are associated with SM including behavioral
inhibition, genetics, and environmental factors.
Behavioral Inhibition
Behavioral inhibition (BI) is a temperament characterized by shyness, apprehension, and withdrawal

in novel situations. Reluctance to speak has been described as a defining feature of BI [51]. Much of
the support for BI as an etiological variable stems from the association between SM and SOP for
which there is a clearly established link with BI [52]. However, there are only a few studies that
empirically address temperament and SM. In one study, individuals with SM had temperaments char-
acterized by difficulty responding to novel situations and difficulty handling transitions and change
[2]. In many reports, children with SM are consistently described as having behavioral or personality
characteristics that resemble BI, such as a lifetime history of shyness or slow-to-warm-up tempera-
ment [6, 52, 53]. Descriptive reports of children with SM also show that they tend to score high on
the “withdrawn/depressed” or “internalizing” scales of socioemotional and behavioral checklists
[14, 42, 54, 55].
Familial/Genetic Vulnerability
The co-occurrence of SM and social anxiety in families suggests a possible genetic etiology. Poor
language production, extreme shyness, and speech and language disorders occurred in 78 % of first-
degree relatives in one sample, with concordance rates of SM of up to 18 % in first-degree relatives
[32]. Another study reported that about 70 % of first-degree relatives of children with SM had a his-
tory of social anxiety and shyness, and 37 % of first-degree relatives had a history of SM [20]. The
rates of avoidant personality disorder (17.5 %) and lifetime generalized SOP (37 %) among parents of
children with SM are higher compared to parents of children without any disorder (4.7 % and 14.1 %,
respectively) [39].
Only one study has looked at genetic susceptibility factors for SM; the sample included 106 indi-
viduals with SM, and results indicated an association between SM and the CNTNAP2 gene, more
specifically the rs2710102 single nucleotide polymorphism (SNP) [56]. The rs2710102 SNP of
CNTNAP2 has been implicated in the developmental language delay component of autism. Findings
216 C.P. Keeton
of this study therefore provide preliminary evidence of a potential shared genetic etiology for autism
spectrum disorders and SM. Without replication, however, it is premature to consider variation of the
CNTNAP2 gene as a risk factor for SM.
Environmental Vulnerability
Families of children with anxiety disorders and SM have been rated by parents as less socially active
and less involved in recreational activities as compared to families of unaffected children [42]. In a
recent study of parent-child interactions, parents of children with SM were rated as significantly more
controlling compared to parents of anxious or unaffected groups [57]. In another study, parents of
children with SM demonstrated higher degrees of monitoring based on a clinician-rated interview, but
there were no differences on self-reported parenting styles among parents with SM and parents with
unaffected children [37]. Clinician-rated measures may therefore be more sensitive to picking up on
impactful parenting behaviors.
One common tendency that contributes to or maintains SM is accommodation by others [55].
Common accommodation behaviors include “mind-reading” or guessing the child’s response instead
of waiting for a verbal response, assuming the child will not answer independently, developing non-
verbal communication habits with the child, labeling the child as shy, and avoiding facilitating social
opportunities such as playdates and camps. Such behaviors reinforce the absence of speech and limit
opportunities to develop, practice, and master social skills.
The behavior of other individuals in the child’s environment may contribute to further silence
through a process of negative reinforcement. When a child is faced with an anxiety-provoking situa-
tion, the behavioral response is speech withdrawal (a form of avoidance or escape). Avoidance or
escape of the situation results in reduced distress, which reinforces the lack of speech. Additionally,
reduced requests for speech over time negatively reinforce the silence. If a child repeatedly does not
respond when a peer says “hello” or asks a question, the peer may stop interacting and soliciting
responses, which negatively reinforces the lack of responding (while also unfortunately reducing
social opportunities).
Assessment
A multi-informant, multi-method approach is recommended for the assessment of SM [4]. Since the
child may not speak much or at all to the clinician, the primary caregiver is typically the main infor-
mant. Information from a daycare provider or teacher is helpful. Assessment methods include observa-
tional methods, interviewing, pencil-and-paper questionnaires, and speech and language assessment.
Observational Methods
An audio or video file of the child speaking comfortably is useful for verifying the child’s capacity for
age-appropriate speech and for evidence of possible communication problems [4]. Many parents
are willing to bring a recording to the evaluation; however, some children protest about showing the
video. In these instances, viewing the video (with or without the child present) can be added to the
exposure hierarchy in behavioral treatment.
Observing the child in person provides valuable information about symptoms and severity. It is
helpful to observe the extent that the child speaks to parents in the waiting room prior to being
greeted by a clinician and to observe changes in behavior upon being greeted. One can also access
other indicators of anxiety such as fidgetiness, tenseness, closeness with caregiver, and social skills
or comfort with the social interaction including eye contact and quality of communication with
the examiner.
Although some children speak comfortably with the examiner or at least answer questions indi-
rectly by whispering responses to a parent, most are not expected to initiate speech or offer responses.
The examiner may avoid direct communication with the child initially in order to reduce the child’s
anxiety; for example, the examiner could offer a child some crayons and paper and invite her to draw
without asking any questions. Direct questions about the child (“What is your name?” “What grade
are you in?”) that are natural in forming a rapport may be less helpful in this instance when the child
does not cope well with being in the spotlight. One alternative strategy is to explain to the child that
the parent will be answering many questions and the child is welcome to talk at any time, especially
if the parent says something that is incorrect.
Some studies have utilized social interaction tasks to code the child’s anxiety severity and related
behaviors. For example, two groups of investigators used blinded observers to rate children’s anxiety
levels and social effectiveness during videotaped experimental role plays and reading tasks involving
same-age peers and unfamiliar adults [9, 19].
Interviews
The clinical interview is an opportunity to assess the family and developmental history, complete a
functional assessment, determine the presence of comorbid problems, and rule out alternative expla-
nations for the problem. It is essential to rule out and/or assess for organic problems (hearing loss,
brain injury) or speech problems that explain the mutism because a diagnosis of SM cannot be given
unless other causes of lack of speech are ruled out. Structured interviews are valuable for obtaining a
thorough impression of the clinical symptoms including likely comorbidities such as SOP or elimina-
tion problems. Two structured interviews that contain modules specific to SM include the Anxiety
Disorders Interview Schedule for DSM-IV [58] and the Preschool Age Psychiatric Assessment [59].
Disorder-Specific Questionnaires
The Selective Mutism Questionnaire (SMQ) is a 17-item parent-report measure designed to assess the
child’s speaking behaviors across three social settings (i.e., school situations, social situations with
family members, and situations outside of school not involving family) [60]. On this measure, parents
respond to questions such as how frequently their “child talks to most peers at school,” by indicating
whether that behavior occurs always, often, seldom, or never. The SMQ has shown excellent internal
consistency and strong convergent and discriminant validity [60, 61]. Scores range from 0 to 51 and
higher scores reflect age-appropriate speaking behavior. Some data suggests that the average summed
total score of a child diagnosed with SM is about 13 [60]. The SMQ has been used to demonstrate
changes in symptoms as a function of treatment [34, 62].
The School Speech Questionnaire (SSQ) was adapted from the SMQ to collect information from
teachers regarding students’ speaking behaviors at school [14]. It includes 10 items rated on the same
0 (“never”) to 3 (“always”) scale as the SMQ, and six of the items are used to compute a total sum
score. Psychometric data on this measure is limited, although the internal consistency in the original
218 C.P. Keeton
sample was good [14]. The SSQ was helpful in showing treatment effects in at least one published
treatment study in which mean scores raised significantly from 0.59 at baseline to 2.68 at the 6-month
follow-up of a behavioral intervention for preschoolers [63].
Speech-Language Assessment
Since assessing for communication problems is an important consideration in SM, it may be neces-
sary to refer the child for a formal assessment by a speech and language pathologist. Often nonverbal
language assessments can be effectively used to screen for problems and help determine if a referral
for additional testing is needed. Two examples include the Peabody Picture Vocabulary Test (PPVT-IV)
[64] and the Children’s Communication Checklist (CCC-2) [65]. The PPVT-IV assesses receptive
vocabulary and yields a standardized score based on the child’s age. Administration involves present-
ing a group of pictures to the child, saying a word that describes one of the pictures, and then asking
the child to point to the picture that the word describes. The CCC-2 is a 70-item parent-report measure
that screens for communication problems and identifies pragmatic language impairments.
Treatment
Although SM is most often conceptualized as an anxiety disorder, significantly less is known about
effective treatments for SM relative to more common anxiety disorders. Most of what we know about
the treatment of SM comes from retrospective record reviews, uncontrolled case studies, single-case
experiments, and a few controlled studies. There are increasing data showing that psychosocial and
pharmacological treatments can be effective with this vulnerable population. Most of these studies
were conducted in small samples that were clinically referred and are more likely to be severe or
difficult to treat compared to the general population of children with SM. Additionally, the majority
of studies have been conducted in school-aged or adolescent populations despite the preschool age
of onset of SM. The goals of treatment are to reduce anxiety and increase the quality and quantity of
speech across people and situations. Remission is achieved when speech gains generalize to real-
world situations and the child demonstrates spontaneous, age-appropriate conversational speech
across contexts.
Psychosocial Treatments
A variety of approaches have been used in the treatment of SM including any combination of behavioral,
cognitive behavioral, psychodynamic, speech-language, and family systems therapies. Behavioral
and cognitive behavioral treatment approaches have received the most research support, produce
positive end-state functioning in children, and are therefore considered the first-line treatment [53, 66].
The high degree of anxiety in the SM population contributes to an underlying rationale for using
cognitive and behavior modification approaches in the treatment.
Treatment duration varies by the study, but the consensus is that psychosocial treatment is likely to
last several months and can be longer than treatment for common anxiety disorders [13]. Since a child
may not speak at all for several treatment sessions, a great deal of time is spent establishing rapport
and ways of communicating. When a child does begin speaking, it is a slow and gradual process
whereby she may speak a few words per session, and it takes many sessions to achieve more fluid or
spontaneous speech and to assist with generalizing those gains to the real world. Commonly used
specific treatment techniques are discussed below.
Graduated Exposure, Shaping, and Stimulus Fading
These exposure-based techniques are based on the theory that mutism is a learned avoidant behavior
that is reinforced by removal of distress following mutism. Exposure is the most often cited technique
in the literature [53, 66]. Graduated exposure targets the problem by teaching approach behavior
(rather than avoidance) to overcome the distress. Exposure involves having the child face anxiety-
provoking or feared speech situations in a gradual way, starting with the least distressing situations
and moving toward increasingly distressing situations. There are two books available that guide parents
on collaborating with the school to assist the child in working through a gradual hierarchy [67, 68].
A related technique, shaping, involves reinforcement for successive approximations of behaviors
that resemble speech. Stimulus fading involves gradually increasing the number of people in a speak-
ing situation, or gradually removing protective factors such as a parent, and has been successful in
increasing the amount of speech and the number of people spoken to across varied settings [69, 70].
Often these strategies are used concomitantly.
Sample in-office exposures include talking openly in clinician’s office to parent without clinician
and gradually fading in clinician and fading out parent, mouthing brief responses through play fol-
lowed by whispering some or all of the response with subsequent increases in volume (e.g., mouthing/
verbalizing “go fish” during card game), showing clinician a home video of self-talking or singing,
answering “yes/no” questions first with gestures followed by progressively louder verbalizations, and
reciting the alphabet or favorite songs. Outside of session, specific daily speech exposures for social
situations including daycare or school are assigned. Sample out-of-session exposures include mouth-
ing words to the morning song with rest of the class, whispering one word to assigned buddy in
response to teacher’s question, voicing a need to teacher, ordering drink at restaurant, and asking an
unknown child his name at a public playground.
Exposure exercises may be problematic for children for whom direct discussion of the mutism or
its treatments is extremely anxiety provoking such that it may be aversive and produce increased anxi-
ety or an oppositional response. In these instances, other behavioral strategies should be prioritized.
Contingency Management
This strategy, typically used in conjunction with exposure exercises, involves the use of rewards to
reinforce efforts and gains toward treatment goals. Rewards range from positive attention, praise,
privileges, to tangible items. Experiential and tangible rewards should be age appropriate, desirable,
and commensurate with the “size” of the completed behavior (i.e., small rewards for small steps and
big rewards for big steps). Examples include sitting in the clinician’s chair, playing a game, going to
the theater, or getting prizes (e.g., stickers, sugarless gum, hair accessory, or craft activity). This strat-
egy also involves using consequences to reduce the mute behavior. Consequences may range from
ignoring the mutism (while attending to speech attempts) to enforcing a punishment as a result of
failed speech in a situation when speech was expected. While there is some evidence that this strategy
results in treatment gains, most clinicians caution against using coercive or aggressive tactics which
will likely exacerbate the problem [2]. Thus, ignoring the mutism while focusing on rewarding speech
attempts is likely a more effective strategy for many children, compared to issuing more serious con-
sequences such as privilege removal. Contingency management is often used in conjunction with
exposure-based practices in order to reward a child’s progress and enhance motivation toward
realizing continued treatment gains. In one small study comparing exposure-only to contingency
management-only, exposure was considered relatively more effective [35].
220 C.P. Keeton
Relaxation Training and Systematic Desensitization
Relaxation training involves teaching the child diaphragmatic breathing and progressive muscle relax-
ation in order to target autonomic arousal and related physiological responses associated with anxiety.
When paired with exposure, the goal is for the child to learn to tolerate increasing levels of anxiety.
This strategy has resulted in positive outcomes such as increased verbalizations at school and number
of individuals spoken to, school attendance, and involvement in extracurricular activities [12].
Self-Modeling
This technique involves splicing an audio or video recording to depict a child speaking in a context in
which she is mute. Also referred to as “audio feedforward” and “video feedforward,” this technique
requires the child to listen to or view the recording several times. The goal is that the child develops
beliefs about her ability to speak as depicted in the recording, followed by actual speaking behaviors.
Published case reports on children aged 5–9 years have paired self-modeling during the course of
treatment with techniques such as stimulus fading, reinforcement including “mystery motivators,”
and fluoxetine [71, 72]. Positive findings were reported including developmentally appropriate speech
that generalized beyond the scenario depicted in the recordings. However, feedforward techniques
were not successful for some children who refused to make the recording [71].
Parent Training
This strategy targets environmental variables associated with the problem. The parents may be encour-
aged to reduce accommodation behaviors, increase opportunities for social interaction outside of
the home, apply reinforcement for the child’s speech outside of the home, model self-exposure to
social-evaluative situations, or model positive self-talk or other coping strategies [54].
Cognitive Restructuring
This technique involves identification of maladaptive thoughts and teaching realistic, coping-focused
thinking. A child who is able to articulate specific worries such as thinking that her voice will sound
funny is in a position to develop positive self-talk or challenge the irrational components of specific
thoughts through Socratic questioning. This technique is best suited toward older children who have
the cognitive maturity to identify anxiety-enhancing thoughts; however, a simplified version for
younger children focused on reflection on past successes with exposures could be helpful [73].
Innovative Psychosocial Strategies
Although there are no published treatment manuals specific to SM, some researchers have adapted
existing evidence-based psychosocial treatments to suit the individual needs of children with SM. One
such manual is Social Effectiveness Therapy for Children (SET-C), a social skills group treatment
with demonstrated efficacy for youth with social anxiety [74]. In a case study of a 10-year-old with SM,
SET-C sessions were adapted to begin with a shaping/warm-up exercise requiring repeated vocaliza-
tion of a sound, a word, and then a sentence, followed by learning a new social skill (e.g., eye contact,
greetings, topic transitions), role playing the new skill, and completing an exposure task. Treatment
also included several parent training sessions and school-based interventions. Although there were a
number of challenges associated with the case, the authors concluded that SET-C could be appropriate
for school-age or adolescent youth who have SM and obvious social anxiety and/or social skills
deficits [54]. Similarly, the Coping Cat manual for child anxiety [75] and modular CBT for child anxiety
[76] are evidence-based treatments that have been applied to SM. The Coping Cat is an individual
treatment that involves teaching the child emotion recognition, cognitive restructuring, problem
solving, and relaxation, followed by graduated exposure. In one case example, this treatment was
adapted for an 8-year-old by increasing parental participation in treatment; after completing the
manual, the child no longer met criteria for SM [77]. Another case report of an 8-year-old utilized a
modular CBT treatment including a focus on psychoeducation, cognitive restructuring, exposure, and
relapse prevention, and resulted in resolution of SM after 21 sessions [55].
The majority of treatment studies have limited representation of preschool children, and a need for
early intervention has been identified because of the early age of onset of SM as well as data showing
more favorable outcomes for younger children [53, 78]. There is one recent behavioral treatment study
that involved seven children with SM aged 3–5 years [63]. This study is further set apart from others
in the emphasis on the importance of treatment setting and a behavioral strategy the authors termed
“defocused communication.” First, treatment started in the home where the child was most comfort-
able and then moved to the kindergarten where symptoms were most impairing. Second, the clinician,
parents, and teacher utilized communication strategies such as sitting beside rather than across from the
child, creating joint attention using an activity the child enjoys rather than focusing on the child, and
thinking aloud rather than asking the child direct questions. These strategies were paired with psycho-
education, stimulus fading, and rewards for weekly or twice-weekly sessions for a maximum of
6 months. At the six months, six out of seven children spoke in all kindergarten settings. At the one year
follow-up, five out of seven children spoke freely in the classroom. This study provides evidence that
behavioral treatment can be favorable for the youngest children diagnosed with SM and articulates
strategies involving treatment setting and communication style that could influence outcome.
Other newly emerging, innovative treatment approaches for SM involve Web-based and group
formats. There is one case of Web-based CBT program used for a 7-year-old that resulted in significant
reductions in anxiety and overall SM symptom severity [79]. One 8-week group treatment focused on
psychoeducation, relaxation exercises, gradual exposure, and rewards resulted in significant increases
in speech production across settings for the five participants (mean age 6.1 years) [62]. Another cogni-
tive behavioral group-based format emphasizing exposure, social skills training, and speech and lan-
guage techniques has resulted in speech inside and outside of treatment for the majority of children
treated [80]. Finally, pilot data on nine children aged 4–7 years shows promise regarding an intensive
1-week group behavioral treatment. This program, “Brave Buddies,” uses a simulated classroom for
children to practice speech and has resulted in increases in spontaneous speech and improvement on
the SMQ school subscale [81].
There is one NIMH-funded randomized controlled trial that tests a 20-session integrated behav-
ioral therapy for children aged 4–8 years, but the results are not yet available (Bergman RL. Personal
Communication, 2011).
Pharmacologic Treatments
Pharmacotherapy is recommended in the treatment of SM generally when psychosocial interventions

are ineffective or when symptoms are chronic and severe [78, 82]. There are currently no medications
that are approved by the United States Food and Drug Administration (FDA) for the treatment of SM.
No large-scale studies of pharmacotherapy for SM have been conducted, and medication effects as
described in the literature tend to be variable. Despite limited data regarding the use and safety of
drugs in the treatment of SM, at least one survey study showed that child and adolescent psychiatrists
222 C.P. Keeton
commonly prescribe psychotropic agents, usually antidepressants, for children with SM [21]. SSRIs
are considered the first-line pharmacologic treatment for SM because of the predominance of reports
in the literature and due to the relative safety and established efficacy of these agents in other child-
hood psychiatric disorders [82]. Since most drug studies have utilized fluoxetine, this is the preferred
agent for children with SM. The choice of agent, however, may be impacted by the presence of
comorbid conditions.
Fluoxetine
Fluoxetine is the most studied SSRI for the treatment of SM. Notably, there is one double-blind,
placebo-controlled treatment study involving 15 children, aged 6 to 11 years [83]. Treatment occurred
for 12 weeks, and the mean maximum dose of fluoxetine was 21.4 mg/day. Fluoxetine-treated sub-
jects showed significant improvement across ratings of mutism and anxiety; however, they remained
highly symptomatic at the end of 12 weeks, and comparisons with the placebo group were not statisti-
cally significant except for parent-reported global improvement. The authors concluded that short-
term fluoxetine was well tolerated and showed benefit but that 12 weeks may be too short a period to
find significant changes. Also, they speculated that early changes may be less evident at school com-
pared to elsewhere (such as in the neighborhood) and that starting treatment during the summer or
early in the school year, before patterns of nonspeaking in the school context have become too
entrenched, may be most beneficial. Additionally, dosing may have been conservative given the severity
of the patient population.
An open trial study of fluoxetine with 21 children, ages 5–14 years, found that an optimal response
at the end of 9 weeks was achieved with 20 mg/day [84]. Significant pre- to posttreatment changes
were found across self- and parent-rated social behavior and anxiety symptoms and clinician-rated
global assessment of functioning and overall improvement. Younger children showed the greatest
improvements. Several case reports focused on fluoxetine described positive outcomes and few side
effects in children [82]. Time to response and treatment duration within the case reports is variable,
with some children beginning to speak after only 2 weeks of fluoxetine treatment and others requiring
6–12 weeks to achieve some benefit.
Sertraline
Sertraline was studied in one double-blind, placebo-controlled multiple baseline trial with five children,
aged 5–11 years, with SM [85]. Children were given 50 mg/day for 2 weeks followed by 100 mg/day
for 8–12 weeks (depending on randomly assigned placebo phase length). Although the internal validity
of the multiple baseline design was not demonstrated (because increased talking behaviors did not
always correspond to the randomly determined onset of medication initiation), all participants showed
rapid improvements in talking behavior in home and community settings, and two of five demon-
strated improved speech in the school context. The two children who no longer met diagnostic criteria
at the end of the 16-week study were the youngest. Children continued to make gradual gains with
continued sertraline treatment post-study.
Paroxetine
A case report study of an 8-year-old girl with SM, SOP, and separation anxiety treated with paroxetine
5 mg/day at bedtime demonstrated an increase in speaking behaviors following 2–3 weeks of
treatment according to parent and teacher report [86]. SOP and separation anxiety resolved as well.
There were no adverse events. The child was treated for 3 years without relapse of symptoms.
Phenelzine
There are two case report studies of phenelzine examining a total of five children (one aged 5 years
6 months, four aged 7 years) [87, 88]. Maximum doses ranged from 22.5 to 30 mg daily. Treatment
duration ranged from 18 weeks to 15 months. The children began talking freely during treatment and
maintained gains following medication discontinuation. One child was followed 8 years after medica-
tion discontinuation and remained free of SM symptoms. The most common side effects included
constipation, insomnia, and weight gain. The authors concluded that phenelzine is effective in treating
SM but should be considered after SSRIs and behavioral treatment because of the possibility of food
and drug interactions. The authors also concluded that phenelzine could be helpful when weight gain
is desirable and that it could help target comorbidities such as enuresis, obsessive-compulsive symp-
toms, and mood symptoms.
Comparative Treatment Studies
There is one study that compared different serotonergic medications to various nonmedication treat-
ments for 17 youth with SM. Children treated with medication were rated by parents and clinicians as
showing superior gains on measures of global functioning and SM symptom severity [34]. Results of
this study should be interpreted with caution due to methodological constraints such as small sample
size, lack of randomization, and heterogeneity of therapies received by the children. However, the
“real-world” treatment design is a feature that lends support to the use of SSRIs as an effective treat-
ment for SM.
Case Follow-up
Behavioral therapy involving Naila, her parents, and teacher was initiated. A functional assessment
conducted with each adult identified behaviors that could unintentionally maintain the mutism, and
alternative adaptive behaviors were identified. For example, rather than continuing to remove privi-
leges from Naila in the absence of speech, the mom agreed to offer Naila labeled praise and rewards
for speech efforts. With the input of Naila’s teacher, the parents and clinician constructed an exposure
hierarchy to begin shaping increased speech within the school context. A contingency management
program was developed such that Naila earned a “brave talk buck,” paper money that she could
redeem for special prizes, each time a step on the hierarchy was completed. The concept of shaping
was modeled in weekly sessions with the clinician, and the parents created daily speech opportunities
for Naila in public.
By the end of the school year, Naila had attended 16 treatment sessions. She had made significant
progress; she spoke while on the playground at school, often whispered responses to the teacher when
one on one, and consistently whispered to select peers. Outside of school, she started playing and
talking with unfamiliar kids in public play areas, spoke some at a birthday party, talked normally with
a librarian and her dentist, and began saying “thank you” or “bye” to store clerks.
224 C.P. Keeton
However, she continued to meet criteria for selective mutism. The family planned to continue the
behavioral strategies through the summer and consult with a psychiatrist regarding medication treat-
ment if she regressed or failed to make additional progress.
Summary
SM is a disabling disorder of childhood that typically onsets during the preschool years and persists
for most children without treatment. SM is best conceptualized as an anxiety disorder and shares
many overlapping features with SOP. Multimodal assessment involving parents, teachers, and the
child is critical. Scientifically rigorous studies are lacking, but the literature indicates that exposure-
based strategies are recommended as the first-line treatment, and treatment with a selective serotonin
reuptake inhibitor is suggested in instances of treatment resistance and/or high symptom severity or
impairment. Evidence from retrospective reports, follow-up studies, and treatment studies suggests
that younger age and lower rates of shyness and familial psychopathology may contribute to more
favorable outcomes. Controlled treatment-outcome studies with well-characterized samples including
young children and standardized diagnostic and treatment procedures are needed to further elucidate
the most effective treatment strategies for children with SM.
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Part III
Assessment and Treatment
Assessment of Anxiety Disorders: Categorical
and Dimensional Perspectives
Yasmin Rey, Carla E. Marin, and Wendy K. Silverman
Abstract This chapter provides an overview of evidence-based instruments for the assessment of
pediatric anxiety disorders from both categorical and dimensional perspectives. The chapter begins
with a brief discussion of a categorical perspective to pediatric anxiety assessment and how interview
schedules best capture this perspective. This is followed by a summary of the most widely used inter-
view schedules to assess pediatric anxiety, including the evidence base for accomplishing specific
assessment goals (i.e., diagnosis and treatment evaluation). The chapter follows with a brief discus-
sion on a dimensional perspective and how rating scales best capture this perspective. This is followed
by a summary of the most widely used rating scales for assessing pediatric anxiety, including research
support for their use across contexts (i.e., identifying and quantifying anxiety, screening, and treat-
ment evaluation). Next is a brief summary of objective measures of pediatric anxiety. The chapter
concludes with a discussion of future research directions.
Keywords Child • Adolescent • Anxiety • Assessment • Evidence base
Pediatric anxiety disorders are among the most common psychiatric disorders affecting children and
adolescents, with prevalence rates ranging from 11 % to 12.3 % in community samples [1] and from
4 % to 45 % in clinical samples [2]. They are associated with significant personal distress and interfer-
ence in functioning (e.g., academic, family, peers) [3]. If left untreated, pediatric anxiety disorders can
lead to other psychopathologic conditions including depression and substance abuse [4–6].
One of the greatest challenges is the appropriate assessment of these disorders both in research and
clinical settings, particularly in light of their high comorbidity with one another and with other diag-
noses. Over the past two decades there has been much attention paid to the development of evidence-
based assessment approaches. Evidence-based assessment is important to ensure that treatment is
targeted to address the most impairing concern, such as anxiety, and that symptoms can be reliably
tracked over time [7].
This chapter provides an overview of evidence-based methods and instruments for the assessment
of pediatric anxiety disorders. Both categorical and dimensional perspectives are considered.
Author Note: All authors affiliated with the Child Anxiety and Phobia Program at the Center for Children and Families
of the Department of Psychology at Florida International University.
This manuscript was supported in part by a grant from the National Institute of Mental Health (R01MH079943).
Y. Rey (*) • C.E. Marin • W.K. Silverman
Florida International University, 11200 SW 8th Street, Miami, FL 33199, USA
e-mail: yrey@fiu.edu
232 Y. Rey et al.
Categorical measures are designed to ascertain appropriate diagnosis or diagnoses. For this purpose,
structured and semi-structured diagnostic interview schedules, administered to the child or adolescent
(from here on referred to as child) and their parents, are used. Dimensional measures assess anxiety as a
continuous measure, providing quantitative information about frequency and severity of symptoms.
Rating scales, completed by multiple informants including the child and his/her parents, are the most
commonly used dimensional measures. For most purposes including initial assessment and treatment
evaluation, the combination of the two is recommended, thereby incorporating both perspectives.
Interview schedules and rating scales are emphasized in this chapter because they are the most
widely used assessment approaches. We provide an evaluative narrative as well as comprehensive
tables that summarize reliability, validity, and utility information. However, such subjective verbal
reports have limitations and do not directly capture two additional aspects within the tripartite con-
ceptualization of anxiety [8], namely, (1) avoidance of anxiety-provoking situations or objects and
(2) physiological reactions such as rapid heartbeat and sweating. To assess behavioral avoidance,
other assessment methods need to be considered such as direct observations. To assess physiologi-
cal reactions, psychophysiological measurements such as heart rate or galvanic skin response need
to be considered. Thus, we include a brief section on these objective measures. There also is growing
interest in assessment methods that are at the crossroads of neuroscience and clinical science such as
brain imaging and laboratory tasks in attention biases. We refer the interested reader to Chap. 2, as
well as Field et al. [9] and Pine [10], for further information on these methods.
It is important to note that all of the categorical and dimensional anxiety measures included in this
chapter have been developed based on the revised third or fourth editions of the Diagnostic and
Statistical Manual of Mental Disorders (DSM-III-R; DSM-IV) [11, 12]. The advent of the fifth edition
of the DSM will likely have implications for existing measures of pediatric anxiety which might
require revision and psychometric reevaluation.
Multi-method and Multisource Assessment of Pediatric Anxiety
It is generally recommended that a multi-method (e.g., diagnostic interviews, rating scales, observations,
physiological measures) and multisource (e.g., children, parents, teachers) assessment approach be
pursued whenever possible [13]. A multi-method assessment approach is recommended for pediatric
disorders, including anxiety, because symptoms typically manifest across different response systems
including the behavioral, the subjective/cognitive, and physiological [8]. The rating scales and
diagnostic interview schedules summarized in this chapter capture these three aspects via subjective
verbal reports and therefore do not directly capture behavioral and physiological reactions of anxiety.
However, more objective measures of these responses are obtained through direct observations and
physiological assessment which are summarized later in this chapter.
A multisource assessment approach is also recommended for pediatric disorders, including anxiety,
because different respondents typically have different perspectives [14]. It is common practice to
obtain information from the child and parent(s) when assessing anxiety. Despite this, there is often
low agreement between child and parent reports [15]. This low agreement has been found for both
dimensional [15] and categorical measures of pediatric anxiety. For example, studies using the Anxiety
Disorders Interview Schedule: Child and Parent versions (ADIS: C/P) [16, 17] have yielded poor
estimates of agreement between children and parents regarding the presence of anxiety diagnoses
[18–20], although child–parent agreement is higher at the symptom level, especially for observable
symptoms [21]. It is less common to obtain information from teachers given the logistical challenges
and the lower reliability of internalizing symptom detection in the school setting [22].
Certain factors (e.g., sex, age, parent psychopathology) have been shown to be related to
child–parent agreement and the relative reliability of respondents’ reports, though these findings have
Assessment of Anxiety Disorders: Categorical and Dimensional Perspectives 233
been inconsistent [23]. Edelbrock [24] found parent reports of internalizing symptoms to be more
reliable than young children’s self-reports, but older children’s self-reports of symptoms were more
reliable than parents’ reports. In contrast, Silverman and Eisen [25] did not find age differences in
parent or child reliability estimates of anxiety symptom reports. In light of these mixed findings, there
is clearly a need to advance our understanding of the conceptual and clinical meaning of child and
parent discordance [26]. However, despite this, it is generally recommended that information be
obtained from both the child and his/her parents in the assessment of pediatric anxiety to obtain as full
and accurate a diagnostic picture as possible.
Categorical Perspective in the Assessment of Pediatric Anxiety Disorders
Consistent with a medical model [27], the categorical perspective is the dominant approach used in
clinical psychology and psychiatry. Clinical disorders are defined by a specific set of symptoms and
criteria, based on the DSM-IV (text revision) [28] or the International Classification of Diseases
(ICD-10) [29]. These diagnostic labels are useful because they provide the field with a common
language to describe psychopathological conditions. This “present/absent” approach implies that
individuals either meet criteria for a disorder or do not and provides less information about subthresh-
old symptoms that lead to significant impairment [30]. Information about such symptoms may be
important for treatment planning [30]. This is where dimensional measures can be useful, as discussed
in the following section.
Semi-Structured and Structured Diagnostic Interview Schedules
In clinical practice, diagnostic interviews are most often unstructured. Clinicians ask a series of questions
that they either learned during their training or have developed over time, aimed at identifying whether
the child meets criteria for any DSM diagnoses. However, in research, semi-structured and structured
interviews are the norm for both initial diagnosis and treatment evaluation [31]. These standardized
interviews have been designed to limit the variability inherent in unstructured clinical interviews by
asking the same questions of all informants and using specific methods to capture the data and record
responses. In addition to the standard questions, semi-structured interviews allow interviewers to ask
follow-up questions to clarify informants’ responses regarding the presence or absence of symptoms.
They require administration by clinically trained interviewers who are knowledgeable in the DSM
and/or ICD. In contrast, structured interviews require that each question be asked verbatim and addi-
tional questions cannot be used to clarify informant responses. Thus, they can be administered by lay
persons and require minimal knowledge of the DSM and/or ICD.
Table 1 [17, 20, 25, 32–47] presents a summary of the most widely used and researched semi-
structured and structured interview schedules, including, when available, reliability estimates obtained
from initial psychometric studies. All of the interview schedules have respective child and parent
versions, which are administered separately. Most can be administered to children between the ages
of 6 and 18 years. The interview schedules’ formats are generally similar. They begin with an intro-
ductory section, which includes questions requesting a brief description of the presenting problems,
as well as questions about school, activities, friendships, and family. This is followed by sections or
modules designed to assess for specific disorders, which typically begin with a small number of
screening questions. If an informant responds “yes” to a screening question, the entire set of questions
for that section is administered, which includes obtaining frequency, intensity, and interference ratings
of endorsed symptoms. If an informant responds “no” to all screening questions, the diagnostic
234
Table 1 Structured and semi-structured diagnostic interview schedules
Ages, Interrater reliability (k [kappa]) Test–retest reliability (k [kappa])

Diagnostic interview years DSM anxiety diagnoses Child Parent Combined Child Parent Combined Studies
Semi-structured
Anxiety Disorders Interview 6–18 Generalized Anxiety Disorder 0.72–0.82 0.78–0.82 0.80–0.90 0.63 0.72 0.80 Lyneham et al. [32]
Schedule for DSM-IV: Obsessive- Compulsive Disorder … 0.91 0.91–0.96 … … … Rapee et al. [20]
Child and Parent Separation Anxiety Disorder 0.70–0.81 0.66–0.86 0.59–0.89 0.78 0.88 0.84 Silverman and Eisen [25]
versions Social Phobia 0.80–0.87 0.63–0.87 0.77–0.82 0.46–0.71 0.54–0.86 0.73–0.92 Silverman and Nelles [17]
Specific Phobia 0.59–1.00 0.33–0.87 0.63–1.00 0.76–0.80 0.65–0.80 0.81–0.84 Silverman et al. [33]
Child and Adolescent 9–17 Generalized Anxiety Disorder … … … 0.79 … … Angold and Costello [34]
Psychiatric Assessment Angold and Costello [35]
Diagnostic Interview for 6–18 Separation Anxiety Disorder … … 0.94 0.32–0.75 … … Boyle et al. [36]
Children and Specific Phobia … … 0.98 0.65 … … Kebede et al. [37]
Adolescents Reich [38]
Schedule for Affective 6–18 Generalized Anxiety Disorder … … 1.00 … … 0.78 Ambrosini [39]
Disorders and Obsessive-Compulsive Disorder … … … … … 0.67–0.74 Ambrosini et al. [40]
Schizophrenia for Post-traumatic Stress Disorder … … … … … 0.60–0.67 Kaufman et al. [41]
School-Age Children Separation Anxiety Disorder … … 0.65–1.00 … … … Shahrivar et al. [42]
Specific Phobia … … 0.64–0.75 … … 0.80
Structured
NIMH Diagnostic Interview 9–17 Generalized Anxiety Disorder … … 1.00 0.38 0.65 0.58 Breton et al. [43]
Schedule for Children Obsessive- Compulsive Disorder … … … 0.63 0.84 0.79 Ho et al. [44].
Version IV Panic Disorder (Agoraphobia) … … … 0.20 … … Roberts et al. [45]
Separation Anxiety Disorder … … 1.00 0.27–0.72 0.44–0.58 0.49–0.80 Schwab-Stone et al. [46]
Social Phobia … … … 0.25–0.44 0.45–0.54 0.44–0.48 Shaffer et al. [47]
Specific Phobia … … … 0.42–0.68 0.55–0.96 0.86
Y. Rey et al.
section may be skipped. Sections covering developmental, medical, and psychiatric history also are
contained in most of the parent versions of the schedules.
Diagnoses are obtained after the separate administration of the child and parent interviews. Both
interviews contain questions that correspond to each criterion required to meet a given diagnosis.
If the required number of criteria is met for a particular diagnostic section in either the child or parent
interview schedule, then a diagnosis is warranted. Separate diagnoses for the child and parent ver-
sions are obtained using diagnostic algorithms completed either by the clinician (e.g., Schedule for
Affective Disorders and Schizophrenia for School-Age Children, [K-SADS]) [39] or by computer
(e.g., The National Institute of Mental Health Diagnostic Interview Schedule for Children for DSM-IV
[NIMH DISC-IV]) [47]. These diagnoses are then combined for a final diagnosis using rules derived
either by the developers of the interview (e.g., ADIS: C/P) [16] or by computerized algorithms
(e.g., DISC-IV) [47].
The ADIS: C/P [16] is the most widely used semi-structured interview in pediatric anxiety disorders
research, including randomized clinical trials. This is likely because it has the most comprehensive
coverage of the DSM anxiety disorders [7]. The ADIS: C/P also includes modules for other common
DSM disorders, such as major depressive disorder (MDD) and dysthymia, as well as externalizing
disorders (e.g., attention deficit hyperactivity disorder, oppositional defiant disorder).
In addition to acquiring information regarding DSM-IV diagnostic criteria, the ADIS: C/P contains
clinician severity rating scales to assess the child’s level of distress and/or impairment in functioning
relating to each disorder using a 0- (none) to 8 (very much)-point scale [7]. The severity ratings
derived by the clinicians are based on the information obtained from both the child and parent inter-
views. Severity ratings of 4 or higher suggest a DSM diagnosis, assuming all diagnostic criteria are
met. When criteria for multiple disorders have been met, the most severe and interfering disorder,
based on the severity rating scale, is considered the primary diagnosis, followed by a ranking of the
other severity ratings (e.g., secondary, tertiary). The ADIS: C/P severity rating scales are also used to
obtain ratings from children and parents of the severity of the child’s fear and/or avoidance in specific
situations. In this way, clinicians can ascertain which symptoms/situations are most severe and should
be targeted in the child’s treatment.
The Child and Adolescent Psychiatric Assessment (CAPA) [35] is a semi-structured interview that
assesses the frequency, duration, and intensity of symptoms associated with over 30 psychiatric
disorders, including the anxiety disorders, according to the DSM-IV and ICD-10. It also covers
a number of disorders that were part of DSM-III-R but are no longer included in the DSM-IV (e.g.,
overanxious disorder [OAD], avoidant disorder [AVD]). The CAPA assesses symptoms of psychiat-
ric disorders that have occurred over the past 3 months, referred to as the primary period. It uses a
modular format, allowing interviewers to administer specific diagnostic modules independently
from the entire interview. Unique to the CAPA is the inclusion of a glossary that provides descrip-
tions of symptoms reported by the child or parent to aid the interviewer in determining the pres-
ence or absence of symptoms. Also included in the glossary are instructions for coding symptom
severity levels.
The Diagnostic Interview for Children and Adolescents (DICA) [38] was designed originally as a
highly structured interview to be administered by lay interviewers; however, successive versions have
rendered the DICA more semi-structured [38]. In addition to a parent version, the DICA has a ver-
sion for children ages 6–12 years old and a version for adolescents ages 13–18 years old. The DICA
covers over 20 psychiatric disorders, including all of the anxiety disorders, using DSM-IV criteria.
Similar to the CAPA, the DICA also covers a number of disorders that were part of DSM-III-R but
are no longer included in the DSM-IV (e.g., OAD, AVD). Diagnoses based on the ICD-10 can be
derived using computer algorithms. The DICA assesses both current psychiatric diagnoses and life-
time diagnoses.
The (K-SADS) [39] is a semi-structured interview that assesses over 30 psychiatric disorders,
including the anxiety disorders. At present, there are three versions available: the K-SADS-Present
236 Y. Rey et al.
State (K-SADS-P-IVR), K-SADS-Epidemiologic (K-SADS-E), and K-SADS-Present and Lifetime

(K-SADS-P/L). The K-SADS-P-IVR assesses frequency and severity of symptoms of psychiatric
disorders, both currently and over the past 12 months, based on the DSM-IV, DSM-III-R, and the
Research Diagnostic Criteria (RDC) [48]. The authors of the current K-SADS-P-IVR also included
the Clinical Global Impressions Scales [49], which are used to measure symptom severity and symptom
improvement. The K-SADS-E (fifth version) and K-SADS-P/L both assess current and lifetime diag-
noses based on the DSM-IV and DSM-III-R. The K-SADS-P/L (version 1.0) is unique in its inclusion
of an 82-symptom screening interview. If a child or parent responds “yes” to the presence of a given
symptom, a supplement with the remaining symptom criteria for the specific disorder is administered.
If a child or parent responds “no” to the screening symptoms, the specific diagnostic supplemental
section is skipped, shortening administration time.
The NIMH DISC-IV [47] was originally designed for epidemiological use, but successive versions
have been used in clinical studies and as an aid to diagnosis in service settings. The DISC-IV is a
structured interview that assesses over 30 psychiatric disorders, including the anxiety disorders, based
on the DSM-IV and ICD-10. The DISC-IV assesses the presence of current diagnoses (within the past
4 weeks at the time of the interview) and diagnoses occurring within the past 12 months. It also
includes an optional module for lifetime diagnoses.
Reliability
Table 1 summarizes the interview schedules’ reliability estimates (kappa coefficients) for specific
anxiety disorders when study sample sizes were sufficient to allow these analyses. Kappa coefficients
(k[kappa]) greater than 0.74 are considered excellent, k[kappa]s between 0.59 and 0.74 are consid-
ered good, k[kappa]s between 0.40 and 0.58 are considered fair, and k[kappa]s <0.40 are considered
poor [50].
As Table 1 shows, estimates of reliability between clinicians (or interrater reliability) have gener-
ally been found to be good to excellent for generalized anxiety disorder (GAD), obsessive-compulsive
disorder (OCD), separation anxiety disorder (SAD), social phobia (SOP), and specific phobia (SP)
(k[kappa]: 0.63–1.00) using the latest version of the ADIS: C/P for DSM-IV [16] and its previous
version for DSM-III-R [17] according to child, parent, and combined child and parent reports (see
Table 1) [17, 20, 32]. The previous version of the ADIS: C/P for DSM-III-R has shown somewhat
lower reliability estimates for some anxiety disorders examined, such as SAD (k[kappa] = 0.59)
found anywhere in the diagnostic profile using combined child and parent reports, and poor to fair
estimates for SP as the primary diagnosis and as a diagnosis anywhere in the profile using child and
parent reports, respectively (k[kappa]: 0.33–0.59) [17, 20].
Test–retest reliability estimates (7–14 day retest interval) for specific anxiety diagnoses using the
ADIS: C/P for DSM-IV and its previous version have generally been found to be good to excellent for
GAD, SAD, SOP, and SP (k[kappa]: 0.63–0.92) according to child, parent, and combined reports (see
Table 1) [25, 33]. However, one study [25] using the previous version of the ADIS for DSM-III-R [17]
found fair reliability estimates for SOP according to child and parent reports (k[kappa]: 0.46 and 0.54,
respectively) (see Table 1).
The reliability of diagnoses has been examined using several versions of the K-SADS (K-SADS-
P-IIIR and K-SADS-IV-R, K-SADS-E, and K-SADS-P/L) in both clinic and community samples
[39–42]. Findings show that interrater and test–retest reliability estimates for anxiety diagnoses based
on combined child and parent reports vary from good to excellent (see Table 1).
One study examined interrater reliability of a number of disorders, including some anxiety disor-
ders, using the DISC-R [51]. Reliability estimates for the anxiety disorders examined, namely, GAD
and SAD, were excellent (see Table 1). This finding is not surprising given the highly structured
nature of the DISC. Retest reliability of diagnoses using the latest version of the DISC (DISC-IV),
as well as previous versions (i.e., DISC-R, DISC 2.1, and DISC 2.3), has been examined in both
clinic and community samples [43–47]. Retest intervals ranged between 1 and 23 days. As Table 1
shows, reliability estimates in the good to excellent range were found for OCD using child, parent,
and combined reports (k[kappa]: 0.63–0.84) [44]. Poor to fair retest reliability estimates were found
across studies for SOP and panic disorder (PD) with agoraphobia using child, parent, and combined
reports (k[kappa]: 0.20–0.54) [45, 47]. Test–retest reliability estimates for GAD, SAD, and SP using
the DISC vary across studies and informants. Test–retest reliability estimates for GAD have been
found to be good using parent report (k[kappa] = 0.65) [46] but poor to modest for child and com-
bined reports (k[kappa]: 0.38–0.58) [45, 47]. Retest reliability estimates for SAD have been excel-
lent for child and combined reports in one study (k[kappa] = 0.72 and 0.80, respectively) [46], but
other studies have found poor to fair estimates for SAD using child, parent, and combined reports
(k[kappa]: 0.27–0.58) [43, 45, 47]. Good to excellent reliability estimates were found for SP using
child, parent, and combined reports in one study (k[kappa]: 0.68–0.96) [47], but other studies
reported only fair reliability estimates for SP using child and parent reports (k[kappa]: 0.42–0.55)
[43, 45].
Less research has been conducted on the reliability of anxiety diagnoses using the CAPA and
DICA [34–38]. Overall, studies show good to excellent (k[kappa]: 0.65–0.98) interrater and retest
reliability estimates [34, 35, 37, 38], except for one study on the child-report version of the DICA,
which found a poor retest reliability estimate of 0.32 for SAD [36]. More research is needed given the
absence of interrater reliability estimates on CAPA- derived anxiety diagnoses and the availability of
retest reliability estimates for child-reported GAD only. Further, interrater and retest reliability esti-
mates are available for a couple of DICA-derived anxiety diagnoses (i.e., SAD, SP) based on com-
bined child and parent reports or child report only.
Validity
Relative to studies examining reliability, fewer studies have examined the validity of anxiety diagno-
ses using interview schedules. Wood et al. [52] examined concurrent validity of ADIS: C/P diagnoses
of GAD, PD, SAD, and SOP in 186 children (ages 8–17 years) referred to an anxiety disorders clinic.
Children and their parents were administered the ADIS: C/P and completed the Multidimensional
Anxiety Scale for Children (MASC) [53]. Findings showed strong convergence between the ADIS:
C/P anxiety diagnoses (except for GAD) and the MASC subscale scores corresponding to the respec-
tive disorders. Findings also supported divergent validity of the ADIS: C/P in the predicted direction.
For example, MASC Social Anxiety subscale scores, but no other subscale scores, were significantly
elevated for children meeting DSM-IV SOP.
Studies of the validity of anxiety diagnoses obtained using the DICA and K-SADS have not shown
such positive results [36, 54]. For example, in a study of 30 clinic-referred children (ages 7–16 years),
poor to modest convergence was found for the presence of any DSM-III anxiety disorder between the
K-SADS and Child Assessment Schedule [54, 55]. In a community sample of 2,317 children (ages
6–16 years), poor convergence was observed between the DICA-R DSM-III-R anxiety diagnoses of
SAD and OAD and subscales corresponding to these disorders on the revised Ontario Child Health
Study Scales [56] (k[kappa] = 0.37 and 0.31, respectively) [36]. Although these findings fail to sup-
port the concurrent validity of these two widely used interviews, it should be noted that the K-SADS
findings were likely impacted by the small sample size and both studies are based on previous editions
of DSM; validity studies using DSM-IV diagnoses and measures are needed.
238 Y. Rey et al.
Alternative Formats
The semi-structured and structured interview schedules summarized above have been most commonly
administered face to face with the interviewer recording the interviewees’ responses using a hard
paper copy of the interview. Several of the interview schedules are available in alternative formats,
though research on these formats is relatively scant.
The DISC-IV (C-DISC-4.0) [47] and the DICA [38], for example, are available in computerized
formats. With the C-DISC-4.0, interviewers read questions from a computer screen and key in responses
given by the child and/or parent. Scoring algorithms are built into the computer program, which gener-
ates a diagnostic report immediately after completion of the interview, thus minimizing interviewer
error. The administration of the DISC-IV is not necessarily straightforward for clinicians (e.g., clini-
cians must follow specific skipping instructions and keep track of informants’ responses to a number of
symptoms to determine if follow-up questions about onset and impairment are warranted). As a conse-
quence, the DISC authors recommend that interviewers using more than a single diagnostic module
employ the C-DISC-4.0 to aid interview administration [47]. Reliability of diagnoses using the
C-DISC-4.0 was examined in one study [57] using the Spanish version of the interview. Test–retest
reliability estimates for the anxiety disorders examined, namely, SAD, GAD, and SOP, were fair to
good (k[kappa]: 0.47–0.66) based on parent report only. Reliability estimates for lifetime diagnoses of
SAD, GAD, and SOP based on parent report were poor to excellent (k[kappa]: 0.27–0.75).
The computerized DICA can be administered by an interviewer or be self-administered. Children
and/or their parents read the interview questions from the computer screen and answer them on their
own. The DICA authors recommend that an interviewer administer the computerized DICA for
younger children, as well as older children or parents with reading difficulties [38]. Only one study
examined the retest reliability (over a 1 week retest interval) of diagnoses using the self-administered
computerized DICA in a sample of clinic-referred children 6–18 years old [58]. Results revealed poor to
modest kappa coefficients for the anxiety disorders examined, namely, OAD, SAD, and post-traumatic
stress disorder (PTSD) (k[kappa]: 0.35–0.50).
In addition to computerized formats, interview schedules can be administered via the telephone.
Telephone assessments are useful when assessing families who reside in geographically distant loca-
tions as well as those with demanding schedules and/or transportation difficulties. Telephone assess-
ments can also be useful for conducting posttreatment or follow-up evaluations. The parent version of
the ADIS:C/P has been used in a telephone format. Lyneham and Rapee [59] compared agreement
between diagnoses (present/absent) derived using a telephone administration of the parent ADIS to
diagnoses derived from standard face-to-face administration of the ADIS:C/P. Kappa coefficients of
agreement were in the good to excellent range for anxiety diagnoses examined, GAD, SAD, SOP, and
SP (k[kappa]: 0.63–0.86). These findings suggest anxiety disorders can be diagnosed using a less
resource-demanding alternative to face-to-face assessments [59]. Similar studies are needed for other
interview schedules, as well as other delivery formats including web-based formats (i.e., Internet
DISC-IV [60]).
Summary
The primary aim of the interviews described above is to diagnose psychiatric disorders as well as to
evaluate diagnostic status at posttreatment. Thus, it is critical that the anxiety diagnoses derived from
these interviews are reliable and valid. The ADIS: C/P is well researched with respect to reliability,
with several studies reporting overall good to excellent retest and interrater reliability estimates.
The DISC is the next most researched interview in terms of retest reliability, with findings generally
showing fair estimates for most of the anxiety disorders examined. Less research has been conducted
on the reliability of anxiety diagnoses using the K-SADS, CAPA, and DICA, but the findings gener-
ally show good reliability estimates for most anxiety disorders examined. Validity data have also been
obtained for the ADIS: C/P, DICA, and K-SADS. The ADIS: C/P has demonstrated strong conver-
gence between anxiety diagnoses examined (i.e., SAD, SOP, PD) and corresponding subscales of the
MASC. In contrast, findings for the DICA and K-SADS have shown poor to modest convergence
between anxiety disorders examined and other measures of anxiety, but these studies were conducted
using previous versions of the DSM and require updating.
Overall, the ADIS: C/P is currently considered the “gold standard” and the most highly recom-
mended interview for the diagnosis of pediatric anxiety disorders. Given most of the ADIS: C/P evalu-
ative research has been conducted in anxiety disorders specialty clinics, more research is needed using
the interview in community clinics where base rates for anxiety disorders are lower than in anxiety
clinics. Also needed is research on the reliability of pediatric anxiety diagnoses with relatively low
base rates such as OCD, PD, and PTSD. Finally, more research is needed on the evaluation of interview
schedules administered in alternative formats.
Dimensional Perspective in Assessment of Pediatric Anxiety Disorders
Within a dimensional perspective, emotional and behavioral problems occur along a continuum of
severity, instead of falling into distinct disorders [61]. As such, the differences between normal and
disordered behaviors are viewed as quantitative rather than qualitative. Within this perspective, symp-
toms of disordered behavior as well as the threshold between normal and disordered behaviors are
derived statistically from large representative samples of children and may vary according to child
sex, age, and, in some cases, ethnicity.
Child and Parent Anxiety Rating Scales
Rating scales are the primary dimensional measure of pediatric anxiety. They are commonly used as
screening tools to identify the presence of anxiety in children and to assess treatment response by
quantifying the degree to which anxiety symptoms or anxious behaviors are present before and after
treatment. Table 2 [62–123] presents the most widely used and researched rating scales for the assess-
ment of pediatric anxiety. Also included in the table are reliability and validity estimates from psycho-
metric studies.
All of the rating scales included in Table 2 are completed by children and/or adolescents, and most
also have accompanying versions that can be administered to parents. The parent versions are identi-
cal to the child versions except the item stems have been changed (e.g., “I” modified to “My child”).
These rating scales yield a total score, as well as subscale scores with higher scores indicating greater
anxiety. Additionally, most have recommended clinical cutoff scores that suggest the presence of an
anxiety diagnosis. (The utility of these clinical cutoffs is discussed later in the chapter.) The scales are
now summarized below.
The MASC [53] contains 39 items that assess major areas of anxiety in children ages 8–19 years.
A parent-report version (parent MASC) has also been examined for parents of children 7–13 years old
[64, 75]. Children rate the frequency of experiences such as “I get scared when my parents go away”
and “I worry about doing something stupid or embarrassing” using a 4-point scale (i.e., never, rarely,
sometimes, often). The MASC contains four subscales: Physical Symptoms, Social Anxiety,
Harm Avoidance, and Separation/Panic. The MASC also contains an Inconsistency Index, to identify
Table 2 Youth and parent anxiety rating scales
240
Rating scale Internal consistency (a) Test–retest reliability Convergent validity (r) Divergent validity (r) Studies
Youth scales
Multidimensional Total: 0.84–0.94 3 weeks (ICCs) With RCMAS, STAIC, With Abbreviated Symptom Baldwin and Dadds [64]
Anxiety Scale for Physical Symptoms (PS): 0.77–0.89 Total: 0.79–0.88 SCARED, SCAS Questionnaire [62] and Fincham et al. [65]
Children (MASC) Social Anxiety (SA): 0.66–0.91 PS: 0.80–0.92 Total: 0.60–0.81 Children’s Depression Grills-Taquechel et al. [66]
Harm Avoidance (HA): 0.53–0.82 SA: 0.79–0.84 PS: 0.44–0.76 Inventory (CDI) [63] Ivarsson [67]
Separation/Panic (S/P): 0.58–0.81 HA: 0.34–0.76 SA: 0.54–0.73 Total: −0.15 to 0.60 Kingery et al. [68]
S/P: 0.85–0.89 HA: −0.13 to 0.43 PS: 0.07–0.66 March et al. [69]
1 month (ICCs) S/P: 0.27–0.58 SA: −0.01 to 0.59 March et al. [70]
Total: 0.73–0.86 HA: −0.04 to 0.32 Muris et al. [71]
PS: 0.73–0.85 S/P: 0.18–0.33 Olason et al. [72]
HA: 0.60–0.73 Osman et al. [73]
SA: 0.75–0.90 Rynn et al. [74]
S/P = 0.74 Villabø et al. [75]
Yao et al. [76].
3 months (ICCs) Yen et al. [77]
Total = 0.93
PS = 0.83; HA = 0.72
SA = 0.83; S/P = 0.93
12 months (rs)
Total = 0.52
PS = 0.47; HA = 0.48
SA = 0.54; S/P = 0.55
Revised Child Anxiety Generalized Anxiety Disorder 1 week (ICCs) With RCMAS: With CDI Chorpita et al. [78]
and Depression (GAD): 0.77–0.86 GAD = 0.79; OCD = 0.65 GAD: 0.65–0.73 GAD: 0.05–0.64 Chorpita et al. [79]
Scales (RCADS) Obsessive-Compulsive Disorder PD = 0.76; SAD = 0.75 OCD: 0.49–0.67 OCD: 0.12–0.64 de Ross et al. [80]
(OCD): 0.73–0.83 SOP = 0.80 PD: 0.59–0.69 PD: 0.20–0.60
Panic Disorder (PD): 0.79–0.88 SAD: 0.58–0.62 SAD: 0.06–0.44
Separation Anxiety Disorder (SAD): SOP: 0.62–0.73 SOP: 0.14–0.60
0.76–0.79
Social Phobia (SOP): 0.82–0.87
Y. Rey et al.
Revised Children’s Total: 0.85–0.92 1 week (rs) With MASC, SCARED, With CDI Ang et al. [81]
Manifest Physiological Anxiety (PA): Total: 0.76–0.88 SCAS, and STAIC Total: 0.56–0.74 Muris et al. [71]
Anxiety Scale 0.67–0.75 PA: 0.73–0.75 Total: 0.58–0.88 PA = 0.61 Reynolds [82]
(RCMAS); Worry (W): 0.77–0.86 W: 0.71–0.85 PA: 0.59–0.85 W = 0.66 Reynolds [83]
RCMAS-2 Social Concerns/Concentration SC = 0.85 W: 0.73–0.84 SC = 0.69 Reynolds and Richmond
(SC): 0.67–0.72 SA = 0.64 SC: 0.64–0.73 [84]
Social Anxiety (SA) = 0.80 2 weeks (rs) Varela and Biggs [85]
Total = 0.68 Winsniewski et al. [86]
PA: =0.61; W = 0.66 Wolfe et al. [87]
SA = 0.61
5 weeks (rs)
Total = 0.77
PA = 0.78; W = 0.63
SC = 0.60
9 months (r)
Total = 0.68
Screen for Child Total: 0.89–0.94 2 weeks ICCs (rs) With MASC, SCAS, With CDI, Conners Attention Birmaher et al. [90]
Anxiety Related Somatic/Panic (S/P):0.70–0.88 Total = 0.57 (0.61) STAIC, RCMAS, Deficit Hyperactivity Birmaher et al. [91]
Emotional Generalized Anxiety (GA): S/P = 0.77 (0.82) Internalizing (INT) Disorder-Adolescent Boyd et al. [92]
Disorders 0.77–0.88 GA = 0.50 (0.52) and Anxious/ Version [89], and Crocetti et al. [93]
(SCARED) Separation Anxiety (SA): 0.54–0.75 SA = 0.46 (0.51) Depressed (AD) Externalizing (EXT) scale Essau et al. [94]
Social Phobia (SOP): 0.72–0.89 SOP = 0.53 (0.55) scales of the Youth of the YSR [88] Hale et al. [95]
School Phobia (ScP): 0.43–0.86 ScP = 0.65 (0.66) Self-Rating Scale Total: 0.13–0.71 Haley et al. [96]
5 weeks ICCs (YSR) [88] S/P: 0.07–0.65 Linyan et al. [97]
Total = 0.86 Total: 0.61–0.87 GA: 0.21–0.69 Muris et al. [98]
Assessment of Anxiety Disorders: Categorical and Dimensional Perspectives
Subscales: 0.70–0.90 S/P: 0.59–0.78 SA: 0.20–0.37 Muris et al. [71]

GA: 0.61–0.84 SOP: 0.08–0.43 Muris et al. [99]
3 months ICCs (rs) Weitkamp et al. [100]
Total = 0.50 (0.57–0.70) SA: 0.47–0.66 ScP: 0.06–0.53
S/P = 0.67 (0.58–0.69) SOP: 0.36–0.66
GA = 0.46 (0.50–0.62) ScP: 0.36–0.58
SA = 0.51 (0.55–0.69)
SOP = 0.24 (0.29–0.83)
ScP = 0.52 (0.46–0.53)
6 months (rs)
Total = 0.47
S/P = 0.38; GA = 0.48
SA = 0.19; SOP = 0.47
ScP = 0.36
241
(continued)
Table 2 (continued)
242
Spence Children’s Total: 0.88–0.94 2–4 weeks (rs) With RCMAS, MASC, With CDI and Depression Brown-Jacobson et al.
Anxiety Scale Separation Anxiety (SA): 0.61–0.85 Total: 0.76–0.86 SCARED, STAIC, Self-Rating Scale [101] [102]
(SCAS) Generalized Anxiety (GA): SA: 0.69–0.76 and YSR INT and Total: −0.03 to 0.72 Essau et al. [94]
0.61–0.86 GA: 0.69–0.78 AD scales SA: −0.12 to 0.58 Hernandez-Guzman et al.
Social Anxiety (SOC): 0.70–0.80 SOC: 0.67–0.79 Total: 0.71–0.92 GA: 0.01–0.60 [103]
Obsessions/Compulsions (O/C): O/C: 0.64–0.77 SA: 0.49–0.68 SOC: −0.09 to 0.70 Ishikawa et al. [104]
0.58–0.84 P/AG: 0.67–0.78 GA: 0.58–0.76 O/C: −0.02 to 0.57 Mellon and Moutavelis
Panic/Agoraphobia (P/AG): PI: 0.72–0.83 SOC: 0.41–0.73 P/AG: −0.01 to 0.66 [105]
0.74–0.89 12 weeks (rs) O/C: 0.52–0.66 PI: −0.21 to 0.53 Muris et al. [71]
Fears of Physical Injury (PI): Total = 0.63 P/AG: 0.56–0.73 Muris et al. [99]
0.53–0.90 SA = 0.52; GA = 0.66 PI: 0.40–0.63 Spence [106]
SOC = 0.75; O/C = 0.69 Spence et al. [107]
P/AG = 0.51; PI = 0.59 Whiteside and Brown
[108]
6 months (rs)
Total = 0.60
SA = 0.57; GA = 0.56
SOC = 0.57; O/C = 0.53
P/AG = 0.45; PI = 0.54
State-Trait Anxiety Trait (T): 0.59–0.91 1 week (ICCs) With RCMAS, MASC, With CDI: Chayawat and Brown
Inventory for State (S): 0.73–0.94 S: 0.32–0.79 SCARED, and T: 0.36–0.74 [109]
Children (STAIC) 15 days (rs) SCAS: Cross and Huberty [110]
T = 0.81; S: 65–0.67 T: 0.58–0.88 Li and Lopez [111, 112]
S: 0.24–0.35 Muris et al. [71]
3 weeks (ICCs) Nelson et al. [113]
T = 0.85; S = 0.55 Papay and Hedl [114]
6 weeks (rs): Papay and Spielberger
T: 0.65–0.71; S: [115]
0.31–0.47 Psychoutaki et al. [116]
Reynolds [82]
Schisler et al. [117]
Spielberger [118]
Parent scales
Multidimensional Total = 0.87–0.90 12 months (rs) With SCAS subscales … Baldwin and Dadds [64]
Anxiety Scale for Physical Symptoms Total = 0.70 Subscales: 0.16–0.74 Villabø et al. [75]
Children-Parent (PS) = 0.77–0.85 PS = 0.66
Version (MASC-P) Harm Avoidance (HA) = 0.70–0.74 HA = 0.56
Y. Rey et al.
Social Anxiety (SA) = 0.86–0.89 SA = 0.68

Separation/Panic (SP) = 0.72–0.77 S/P = 0.70
Revised Child Anxiety Total = 0.95 2 weeks (rs) With CBCL subscales With DSM Affective Ebesutani et al. [119, 120]
and Depression Total Anxiety = 0.94 GAD = 0.81 (i.e., INT, AD, and Problems scale of CBCL
Scale- Parent Generalized Anxiety Disorder MDD = 0.83 AP): Total Anxiety: 0.55–0.56
Version (GAD): 0.82–0.88 OCD = 0.75 Total Anxiety: GAD = 0.53
(RCADS-P) Major Depressive Disorder (MDD): PD = 0.69 0.62–0.76 OCD = 0.32
0.80–0.83 SOP = 0.79 GAD: 0.71–0.73 PD = 0.47
Obsessive-Compulsive Disorder SAD = 0.89 OCD = 0.40 SOP = 0.46
(OCD): 0.74–0.84 PD: 0.57–0.60 SAD = 0.42
Panic Disorder (PD): 0.71–0.81 SOP: 0.60–0.65
Social Phobia (SOP): 0.84–0.88 SAD: 0.59–0.69
Separation Anxiety Disorder (SAD):
0.72–0.83
Screen for Child Total = 0.90 … … … Birmaher et al. [91]
Anxiety Related
Emotional
Disorders-Parent
Version
(SCARED-P)
Spence Children’s Total: 0.89–0.93 … With Negative With AFARS Positive Brown-Jacobson et al.
Anxiety Scale- Separation Anxiety (SA): 0.74–0.90 Affectivity and Affectivity subscale and [102]
Parent Version Generalized Anxiety (GA): Physiological CBCL EXT scale Nauta et al. [122]
(SCAS-P) 0.67–0.91 Arousal subscales of Total: −0.21 to 0.33 Whiteside and Brown
Social Anxiety (SOC): 0.74–0.92 Affect and Arousal SA = −0.14 [108]
Panic/Agoraphobia (P/AG): Scale (AFARS) GA = −0.22
0.61–0.92 [121] and CBCL SOC = −0.27
Fear of Physical Injury (PI): INT scale
Assessment of Anxiety Disorders: Categorical and Dimensional Perspectives
P/AG = −0.18
0.47–0.83 Total: 0.37–0.59 PI = 0.03
Obsessions/Compulsions (O/C): SA: 0.28–0.36 O/C = −0.13
0.74–0.92 GA: 0.38–0.40
SOC: 0.38–0.48
P/AG: 0.25–0.27
PI: 0.12–0.28
O/C: 0.16–0.19
State-Trait Anxiety Total: 0.84–0.91 8 weeks (ICCs) With CBCL AD Scale With CBCL AB and Southam-Gerow et al.
Inventory for Total: 0.71–0.75 Total: 0.50–0.65 Delinquent Behavior [123]
Children- Parent 12 months (ICCs) scales
Report-Trait Total: 0.68–0.76 Total: −0.03 to 0.21
Version
(STAIC-P-T)
243
244 Y. Rey et al.
inconsistencies in responses. In addition, the MASC contains two embedded subscales: a 12-item
Anxiety Disorders Index and a 10-item short form (MASC-10). The 12-item Anxiety Disorders Index
was empirically derived to discriminate between children with anxiety disorders from children with
other disorders. Studies have found that children with anxiety disorders score significantly higher on
the Anxiety Disorders Index than children with other psychiatric disorders (e.g., depressive disorders)
[66, 72]. The MASC-10 was designed for purposes such as treatment monitoring and evaluation [70].
Norms for the MASC based on a large school sample of children (N = 2698; 8–19 years old) are avail-
able separately for each sex and three age groups (8–11 years, 12–15 years, and 16–19 years).
A T-score above 65 on the MASC total indicates clinically significant levels of anxiety [53]. There are
no norms or suggested clinical cutoff scores available for the parent MASC.
The Screen for Child Anxiety Related Emotional Disorders (SCARED) [90, 91] contains 38 items
and can be administered to children ages 8–19 years (and to parents of children 6–18 years for the
parent SCARED) [91]. Children rate the frequency of experiences over the past 3 months such as
“It is hard to talk with people I don’t know well” and “I follow my mother or father wherever they go”
using a 3-point scale (i.e., not true or hardly ever true, somewhat true or sometimes true, very true or
often true). In addition to the total scale, the SCARED contains five subscales: Somatic/Panic,
Generalized Anxiety, Separation Anxiety, Social Phobia, and School Phobia. The original SCARED
was subsequently revised to include an additional 3 items because the Social Phobia Scale did not
discriminate between children with SOP from children with other anxiety disorders [91]. There are no
norms available for the SCARED. However, one study using a sample of 190 clinic-referred children
(9–19 years old) and their parents determined that a cutoff score of 25 optimally discriminated between
anxiety and non-anxiety, anxiety and depression, and anxiety and disruptive disorders [91]. There are
no norms or suggested clinical cutoff scores available for the parent SCARED.
In addition to the revised 41-item SCARED, there is another revised version of the SCARED that
contains 66 items [124]. In this version, the School Phobia subscale was removed (i.e., these items
were added to the Separation Anxiety subscale) and five additional subscales were added: SP-Animal
type, SP-Blood Injection Injury type, SP-Situational Environment type, PTSD, and OCD. The 66-item
revised version of the SCARED has been used less frequently than the 38- and 41-item versions. (See
Muris et al. [124] and Muris and Steerneman [125] for examples of studies evaluating the 66-item
version.)
The Spence Children’s Anxiety Scale (SCAS) [107, 126] contains 44 items and can be administered
to children ages 7–18 years (and to parents of children ages 6–18 years using the parent SCAS) [122].
Thirty-eight of the items assess symptoms of anxiety; six are filler items to reduce negative response
biases. Children rate the frequency of experiences such as “I worry that I will do badly at my school-
work” and “I am scared of the dark” using a 4-point scale (i.e., never, sometimes, often, and always).
In addition to the Total Anxiety scale, the SCAS contains six subscales: Separation Anxiety, Generalized
Anxiety, Social Anxiety, Obsessions/Compulsions, Panic/Agoraphobia, and Fears of Physical Injury
(which maps onto SP). Norms for the SCAS based on a large school sample of Australian children
(N = 4,916) are available separately by sex and two age groups (8–11 years; 12–15 years). A T-score
of 65 on the SCAS total or subscales indicates clinically significant levels of anxiety. Norms based on
a Dutch school-based sample of 745 parents of children ages 6–18 years are available for the parent
SCAS, separated by sex, two age groups (6–11 years and 12–18 years), and by anxiety disorder status
(with vs. without) [122]. Although norms are available, there are no suggested clinical cutoffs for the
parent SCAS.
The Revised Child Anxiety and Depression Scale (RCADS) [78, 79] contains 47 items and can be
administered to youth ages 6–18 years (and to parents of children ages 6–18 years using the parent
RCADS) [119, 120]. Children rate the frequency of experiences such as “I am afraid to talk in front
of class” and “I feel nothing is much fun anymore” using a 4-point scale (i.e., never, sometimes, often,
always). In addition to the total scale and Total Anxiety scale, the RCADS contains six subscales:
SAD, SOP, GAD, PD, OCD, and MDD. The RCADS is a revised version of the SCAS designed to
broaden the assessment beyond anxiety disorders to depressive disorders by including an MDD sub-
scale. In addition to an MDD subscale, an important difference between the RCADS and the original
SCAS is the GAD subscale: Items were added to the RCADS (replacing items from the original
SCAS) that are more consistent with DSM-IV GAD criteria. Another important difference between
the RCADS and SCAS is that the RCADS does not contain a Fear of Physical Injury subscale.
Norms based on a school sample (N = 1887) are available for the RCADS, separated by sex and
grade [79]. Clinical cutoff scores on the subscales were derived using a sample of 513 clinic-referred
children [78]. A score of 10 or higher on the SOP subscale indicates a diagnosis of SOP; a score of 7
or higher on the GAD subscale indicates a diagnosis of GAD; a score of 5 or higher on the SAD or
OCD subscale indicates a diagnosis of SAD and OCD, respectively; and a score of 12 or higher on the
PD subscale indicates a diagnosis of PD. Norms based on a school-based sample of 967 parents of
children ages 6–18 (N = 1,887) are available for the parent RCADS, separated by sex and grade [120].
Clinical cutoff scores on the subscales were derived using a sample of 490 parents of clinic-referred
children ages 6–18 [119]. A score of 12 or higher on the SOP subscale indicates a diagnosis of SOP;
a score of 6 or higher on the GAD subscale indicates a diagnosis of GAD; a score of 4 or higher on
the SAD or OCD subscale indicates a diagnosis of SAD and OCD, respectively. A cutoff score for the
PD subscale was not derived in this study.
The Revised Children’s Manifest Anxiety Scale (RCMAS) [84] has a long history in pediatric anxi-
ety assessment and treatment evaluation research. The RCMAS is a revised version of the original
Children’s Manifest Anxiety Scale [127], a downward extension of the Manifest Anxiety Scale for
adults [128]. The RCMAS contains 37 items and can be administered to children ages 6–19 years.
Respondents indicate “yes” or “no” to items such as “I often worry about something bad happening
to me” and “I am afraid of a lot of things.” In addition to the Total Anxiety scale, the RCMAS contains
three subscales: Physiological Anxiety, Worry/Oversensitivity, and Social Concerns. The RCMAS
also contains a Lie Scale consisting of 9 items (e.g., “I am always good”). High Lie Scale scores may
call into question the validity of the ratings and suggest the consideration of alternative sources of
information. The Lie Scale also can be viewed as an indicator of social desirability [84, 129, 130].
Norms based on a large community sample of children (N = 4,972; ages 6–19 years) are available
separately by sex, age (6–8 years, 9–14 years, 15–19 years), and race (white and black). A T-score
on the Total Anxiety scale greater than one standard deviation above the mean (T > 60) indicates clini-
cally significant levels of anxiety [84].
Recently, the RCMAS was revised from its previous 37-item version to a 49-item version (RCMAS-2)
[131]. Like the RCMAS, the RCMAS-2 has a “yes/no” response format and yields a Total Anxiety
score. The RCMAS-2 also contains three subscales: Physiological Anxiety, Worry, and Social Anxiety.
The latter subscale replaced the RCMAS Social Concerns subscale. The RCMAS-2 also includes a
new 10-item content-based cluster that assesses performance anxiety. In addition, by administering
only the first 10 items, the RCMAS-2 can be used as a short form, which takes about 5 min to
complete.
The RCMAS-2 eliminated the 9-item RCMAS Lie Scale and now contains a “Defensiveness
Scale.” The Defensiveness Scale consists of 9 items that assess whether children’s responses have
been given in a defensive manner, with the aim of presenting themselves in a positive light (i.e., social
desirability). Higher scores on this scale indicate higher levels of defensiveness. The RCMAS-2 also
contains a newly added Inconsistent Responding Index, which assesses inconsistency in responses to
nine pairs of items. More pairs of inconsistent items suggest greater likelihood that the child or ado-
lescent is responding randomly or without regard to the item’s content.
Norms based on a large representative US sample of children (N = 3,086; 6–19 years old) are avail-
able for the RCMAS-2, separately by sex and age (6–8 years; 9–14 years; 15–19 years) [131].
A T-score on the Total Anxiety scale greater than 1 standard deviation from the mean (T > 60) indi-
cates clinically significant levels of anxiety. The reliability and validity of the RCMAS-2 were evalu-
ated using the same sample of children from which the norms were derived as well as a school sample
246 Y. Rey et al.
of children from Singapore [81]. Findings thus far show the RCMAS-2 yields similar reliability and
validity estimates as the previous version.
Similar to the RCMAS, the State-Trait Anxiety Inventory for Children (STAIC) [118] has a long
history. A downward extension of the adult State-Trait Anxiety Inventory [132], the 20-item STAIC
assesses chronic (trait) and acute (state) symptoms of anxiety in children ages 8–15 years. An exam-
ple of an item that assesses trait anxiety is “I worry about things that may happen.” An example of an
item that assesses state anxiety is “I feel like crying.” Children rate the frequency of these experiences
using a 3-point scale (i.e., hardly ever, sometimes, often). Norms based on a large US school sample
(N = 1,551, 9–12 years old) are available, separately for sex and each grade (4th–6th grade) [118].
A T-score greater than 1 standard deviation above the mean (T > 60) indicates clinically significant
levels of anxiety [118]. Unlike the anxiety rating scales summarized thus far, the STAIC is mainly
used for the assessment of trait anxiety instead of clinical symptoms of anxiety. As such, it is not as
widely used in the assessment of treatment outcomes as the other measures.
The parent STAIC [123] includes only the Trait scale (STAIC-P-T) and can be administered to
parents of children ages 7–15 years old. The STAIC-P-T includes six additional questions that assess
several child anxiety-related physiological responses (e.g., dry mouth, jittery, headaches) from the
parent’s perspective. Currently, there are no norms or suggested clinical cutoff scores available for the
parent STAIC-P-T.
Reliability
Table 2 summarizes the internal consistency and retest reliability estimates found across studies for
the child and parent rating scales described above. Internal consistency (alpha) coefficients provide a
measure of how well the items on a particular measure are related to one another and are likely to be
assessing the same or similar constructs. Alpha coefficients >0.80 are generally considered high;
alphas between 0.70 and 0.80 are moderate; and alphas <0.70 are low [133].
As Table 2 shows, alpha (a) coefficients for the self-report scales’ total scores are generally above
0.80. Most subscales have been shown to have internal consistency alpha coefficients between 0.70
and 0.94, although alphas lower than 0.70 have been reported for subscales of the MASC, RCMAS,
SCARED, SCAS, and STAIC (see Table 2). Alpha coefficients for the parent scales’ total scores are
all above 0.80; for most of the subscales, alpha coefficients range from 0.70 to 0.92, though alphas
lower than 0.70 have been reported in some studies for the Generalized Anxiety, Panic/Agoraphobia,
and Physical Injury subscales of the parent SCAS (see Table 2). Overall, all of these pediatric anxiety
scales appear to have a reasonable degree of internal consistency.
Test–retest reliability refers to the consistency of a given measure across time. Estimates used to
examine retest reliability of dimensional measures include the intraclass correlation coefficients
(ICCs) and/or Pearson’s r; both estimates indicate the strength of correspondence between scores on
a given measure administered to the same individuals across two different points in time. ICCs >0.74
are excellent, ICCs between 0.59 and 0.74 are considered good, ICCs between 0.40 and 0.58 are fair,
and ICCs <0.40 are poor [50]. Pearson’s r values > than 0.50 are considered large in magnitude; val-
ues between 0.30 and 0.50 are moderate; values < 0.30 are small [134]. ICCs and rs have been reported
for the child rating scales in Table 2 using retest intervals of varying lengths (e.g., RCMAS intervals
have ranged from 1 week to 9 months). As Table 2 shows, ICCs for the child rating scales’ total and
subscale scores are generally in the good to excellent range across retest intervals, and Pearson’s r
values are generally large in magnitude (above 0.50). More modest estimates have been reported in
several studies for the SCARED total score and some subscales of the SCARED, MASC, and SCAS
(see Table 2).
Retest reliability estimates (ICCs or Pearson’s r) are available only for the parent MASC, RCADS,
and STAIC (Trait scale), with estimates ranging from 0.56 to 0.89 for the total scores and subscale
scores across different retest intervals (i.e., 2 weeks, 8 weeks, and 12 months) (see Table 2). Overall,
scores obtained on the child and parent rating scales listed in the table are generally reliable, which is
desirable given that clinical levels of untreated child anxiety would not be expected to change over
time. Additionally, good retest reliability is essential if measures are to be used to assess treatment-
related changes over time.
Convergent and Divergent validity
Table 2 summarizes convergent and divergent validity estimates found across studies. Convergent
validity refers to the degree to which a given measure is correlated with other measures that assess
related constructs. Convergent validity is supported when scores on two related measures (e.g., two
anxiety rating scales) yield large correlation (r) coefficients. Divergent validity refers to the degree to
which a given measure is not correlated with measures that assess unrelated constructs. Divergent
validity is supported when measures of unrelated constructs (e.g., an anxiety rating scale and an
aggression rating scale) show relatively lower correlations than measures of related constructs (e.g., two
anxiety rating scales).
As Table 2 shows, all of the child rating scales exhibit adequate convergent validity in that the total
scales and most of the subscales correlate significantly with other measures of anxiety (e.g., RCMAS,
SCAS, SCARED) (rs usually exceed 0.50) (see Table 2). The MASC’s Harm Avoidance scale, however,
has consistently yielded low or nonsignificant correlations with other measures of anxiety (rs: −0.13 to
0.43) [64, 69, 71]. The parent rating scales also exhibit convergent validity in that the total scales and
most subscales significantly correlate with other parent anxiety scales (rs: 0.16–0.76) (see Table 2).
Similar to the child MASC, the Harm Avoidance subscale of the parent MASC has shown relatively low
correlations with the parent version of the SCAS (rs: 0.16–0.28) [64] (see Table 2). It is therefore not
recommended that clinicians use this specific subscale as the sole measure of child anxiety.
In terms of divergent validity, Table 2 shows the MASC’s and SCARED’s total scales and sub-
scales have yielded low or nonsignificant correlations with child-report measures of externalizing
symptoms (rs: −0.01 to 0.24) [69, 92] (see Table 2). However, divergent validity of the child scales
has been limited in regard to depressive symptoms, which is likely due to the substantial symptom
overlap between anxiety and depression. Significant correlations (often exceeding rs of 0.50) have
been found between most child anxiety rating scales and self-report measures of depression (see
Table 2). Although more research is needed, the RCADS may be a more useful measure than other
anxiety rating scales for distinguishing between anxiety and depressive symptoms in that nonsignificant
correlations have been found between the RCADS anxiety subscales (except PD scale) and the
Children’s Depression Inventory (CDI) [63, 78]. The parent SCAS and STAIC (Trait) have shown
good divergent validity as evidenced by low or nonsignificant correlations with parent rating scales of
child-externalizing symptoms (rs: −0.03 to 0.33) [108, 122, 123]. The parent RCADS total anxiety
scale and subscales, however, have shown significant correlations with parent measures of depression
(rs: >0.50) suggesting poorer divergent validity (see Table 2) [119, 120]. Divergent validity estimates
have not been reported for the parent MASC or SCARED.
Discriminant Validity
The terms divergent and discriminant validity are often used interchangeably in the literature. In this
chapter, however, divergent validity is evidenced by lower correlations with measures of unrelated
constructs than with measures of related constructs. Alternatively, discriminant validity is used when
referring to a measure’s ability to discriminate, or differentiate, children with different pediatric
disorders. The availability of rating scales that can discriminate pediatric anxiety disorders from other
248 Y. Rey et al.
disorders is important given anxiety disorders are highly comorbid with other anxiety, depressive, and
externalizing disorders [6].
Discriminant validity has been examined for all of the self-rating scales and some of the parent
rating scales, with varied findings. For example, the RCMAS and STAIC have been found to discrimi-
nate between children with anxiety disorders from children with no disorders, and children with
externalizing disorders, but not children with depressive disorders [135]. The MASC and SCARED
total scales and subscales (except the MASC Physical Symptoms subscale) discriminate between
children with anxiety disorders and those with no disorders [75]. The MASC total scale and subscales
(except Harm Avoidance and Separation/Panic subscales in one study [80]) have been shown to
discriminate between children with anxiety disorders and those without anxiety disorders [66, 77].
In addition, the MASC total scale and subscales (except Physical Symptoms subscale) can discriminate
between children with anxiety disorders and those with depressive disorders [74]. The SCARED total
scale and subscales also can discriminate children with anxiety disorders from those with disruptive
disorders (except the Separation Anxiety subscale in one study [91]) and depressive disorders (except
the Generalized Anxiety and School Phobia subscales in one study [97]) [90, 91, 97].
The total scale and subscales of the parent MASC (except the Separation/Panic subscale) and parent
SCAS also have been shown to discriminate between children with anxiety disorders and those with
no disorders [75, 108, 122]. Similar to the child SCARED, the parent SCARED also discriminates
children with anxiety disorders from those with other psychiatric disorders. Specifically, the parent
SCARED total scale and Somatic/Panic and Separation Anxiety subscales discriminate between anxi-
ety and depressive disorders [91]. The parent SCARED total scale and subscales (except the Social
Phobia subscale) also discriminate well between children with anxiety disorders and those with
disruptive disorders [91].
Some of the MASC, SCARED, and SCAS subscales and all of the RCADS disorder-specific sub-
scales show good discriminant validity between children with specific anxiety disorders and healthy
comparisons [52, 66, 78, 90, 102]. Findings have been inconsistent for some subscales of the MASC
and SCARED. For example, the MASC Harm Avoidance subscale was found to discriminate children
with GAD from children without GAD in one study [66] but not others [52, 75]. Similarly, Birmaher
et al. [90] found the SCARED Somatic/Panic, Generalized Anxiety, and Separation Anxiety subscales
discriminated between children with PD, GAD, and SAD, respectively, from children without these
disorders. Although findings regarding the Somatic/Panic and Generalized Anxiety subscales were
replicated in Birmaher et al. [91], discriminant validity of the Separation Anxiety subscale was not
found. Instead, the Social Phobia subscale showed good discrimination between children with SOP
from children without SOP, which had not been demonstrated previously.
Some of the parent MASC, SCARED, and SCAS subscales have also been found to discriminate
between children with specific anxiety disorders corresponding to the respective subscales and those
without the disorders. For example, the parent MASC Separation/Panic subscale can discriminate
between children with SAD and those without SAD; the Social Anxiety subscale can also discrimi-
nate between children with and without SOP [75]. In addition, the parent SCARED Somatic/Panic
subscale can discriminate between children with and without PD, and the Separation Anxiety
subscale can discriminate between children with and without SAD [91]. Similar to the child version,
the Separation Anxiety, Social Anxiety, and Obsessions/Compulsions subscales of the parent SCAS
discriminate well between children with the anxiety disorders corresponding to the respective sub-
scales (i.e., SAD, SOP, OCD) from those without these disorders [102, 122]. The parent RCADS
anxiety subscales also have been found to discriminate children with specific anxiety disorders cor-
responding to the respective subscales, as well as children with depressive disorders [119]. Research
is needed to examine the discriminant validity of the parent STAIC (Trait).
In sum, both the RCMAS and STAIC are useful scales to discriminate between children with anxiety
disorders from children with no disorders. However, to discriminate between children with anxiety
disorders from children with other disorders, including externalizing and depressive disorders, the
child and parent versions of the MASC and SCARED are recommended. Further, the child and parent
MASC and SCARED, as well as the child and parent SCAS and RCADS, can discriminate among
specific pediatric anxiety disorders. Caution is warranted, however, in drawing conclusions about the
discriminant validity of certain subscales of the child MASC (e.g., Harm Avoidance subscale) and
child SCARED (e.g., Separation Anxiety subscale) given the inconsistencies across studies.
Screening
Anxiety rating scales are often used to screen for clinical levels of anxiety in children. As such, it is
important that studies evaluate the accuracy of anxiety rating scales in identifying children with an
anxiety diagnosis. However, few studies have examined anxiety rating scales’ sensitivity and
specificity for screening purposes. Sensitivity refers to the percentage of children with an anxiety
diagnosis who scored at or above a specified cutoff score on an anxiety rating scale. Specificity refers
to the percentage of children without an anxiety diagnosis who scored below the clinical cutoff score
on an anxiety rating scale. Even less research attention has been paid to positive and negative predic-
tive power of these scales. Positive predictive power refers to the percentage of children who score at
or above the clinical cutoff score who received an anxiety diagnosis. Negative predictive power refers
to the percentage of children who score below the clinical cutoff score on an anxiety measure who did
not receive an anxiety diagnosis.
The scant research conducted on the screening utility of anxiety rating scales suggests that the
cutoff scores provided by the older anxiety rating scales, namely, the RCMAS and STAIC, are less
likely to correctly identify children with an anxiety disorder than the newer anxiety rating scales [136,
137]. For example, in a sample of inpatient children (6–13 years old), Hodges [137] found the cutoff
scores (T > 60) of the RCMAS and STAIC total scales yielded sensitivity rates of 34 % and 42 %,
respectively.
Recent research using the child and parent versions of the SCAS in a clinic-referred sample [102]
revealed that, on average, the subscales’ cutoff scores (T > 65) yielded a sensitivity rate of 64 % and
74 %, respectively, which was higher than rates obtained in studies using the STAIC or RCMAS.
However, both the child and parent SCAS subscales on average yielded a relative positive predictive
value of 43 %. Thus, about 57 % of children who had scored at or above the clinical cutoff score on
the child and parent SCAS subscales did not receive an anxiety diagnosis.
Several screening evaluation studies have used receiver operating characteristic (ROC) analyses.
ROC analyses yield an area under the curve (AUC), which is an estimate of a rating scale’s overall
diagnostic accuracy across the whole range of scores on the scale. Generally, AUC values between
0.50 and 0.70 indicate low accuracy, values between 0.70 and 0.90 indicate moderate accuracy, and
values 0.90 or greater indicate high accuracy [138]. Because the whole range of scores on a given
measure are considered, ROC analyses can also identify clinical cutoff scores on individual rating
scales that maximize both sensitivity and specificity.
Several studies using ROC analyses have been conducted with the MASC in samples of commu-
nity and clinic children [73–75, 139, 140]. Overall, the child and parent MASC total scores have low
to moderate diagnostic accuracy in identifying children with anxiety disorders (AUCs: 0.60–0.82).
One study of adolescent inpatients found that the total score had high accuracy for screening children
with any anxiety disorder (AUC = 0.91) [73]. The child and parent MASC subscales also have shown
low to moderate diagnostic accuracy in identifying children with specific anxiety disorders corre-
sponding to the respective subscales (AUCs: 0.51–0.84) [75, 140]. Together, the MASC may be more
useful for screening children with more severe levels of psychopathology than children with less
severe levels of psychopathology.
Less research using ROC analyses has been conducted on the RCMAS and the child and parent
versions of the SCARED and RCADS, and there have been no studies using ROC analyses on the
250 Y. Rey et al.
child and parent versions of the SCAS or STAIC. One study that used ROC analyses on the RCMAS in
a community sample of adolescents found that the Total Anxiety score had low accuracy in identifying
the adolescents with anxiety disorders (AUCs: 0.51–0.67) [139].
In terms of the SCARED, Birmaher et al. [90] found that total score and subscale scores had moder-
ate accuracy for discriminating children with an anxiety disorder from those without anxiety disorders
(AUCs: 0.66–0.86) and from those with disruptive disorders (AUCs: 0.68–0.78). The SCARED had
low accuracy for discriminating between anxiety and depressive disorders (AUC = 0.60). In a subse-
quent study, Birmaher et al. [91] used ROC analyses to determine the cutoff score that would maxi-
mize both specificity and sensitivity. A cutoff score of 25 yielded a sensitivity rate of 71 % and
specificity rates that ranged from 61 % to 71 % for discriminating between children with anxiety
disorders and those with depressive and disruptive disorders. The parent SCARED has been found to
discriminate pediatric anxiety from disruptive disorders, but not depression (AUC = 0.59) [91].
In terms of the RCADS, Chorpita et al. [78] used ROC analyses to identify cutoff scores that maxi-
mize sensitivity and specificity. Cutoff scores identified for each of the RCADS anxiety scales yielded
sensitivity rates of 59–78 % and specificity rates of 64–92 % for screening specific anxiety disorders
corresponding to the subscales. Using ROC analyses to examine the parent RCADS, Ebesutani et al.
[119] showed that the cutoff scores identified for the RCADS-P anxiety subscales yielded sensitivity
rates ranging from 71 % to 92 % and specificity rates ranging from 73 % to 86 % for screening specific
anxiety disorders corresponding to the subscales.
In summary, the older scales such as the RCMAS and STAIC have limited utility for screening
anxiety disorders in children. The newer scales such as the child and parent SCAS, SCARED, and
child and parent RCADS have reported higher sensitivity rates than the RCMAS and STAIC. However,
when overall diagnostic accuracy of a rating scale has been evaluated using ROC curves, findings
generally show that the rating scales examined (i.e., RCMAS, MASC, SCARED) have low to moder-
ate accuracy in screening anxiety disorders in children. Given these findings, the evidence is not firm
that the scales summarized are useful for screening purposes. However, the rating scales do provide
essential dimensional information about child anxiety and should be used as part of a comprehensive
battery, which also includes administration of a diagnostic interview to ensure that no children who
have a diagnosis are missed if only an anxiety rating scale is used.
Measuring Treatment Effects
The RCMAS has been used in most of the pediatric anxiety clinical trials and has been consistently
found to be sensitive to treatment change [7]. As indicated earlier, the STAIC has not been used as
frequently as the RCMAS for treatment evaluation because it focuses on trait anxiety rather than clini-
cal anxiety symptoms. The newer scales such as the MASC, SCAS, SCARED, and RCADS have
been used frequently in recent pediatric anxiety trials and also show sensitivity to treatment change
[141–144]. Similarly, the parent versions of the SCARED, SCAS, and MASC have been used in sev-
eral pediatric anxiety clinical trials, with findings generally showing good sensitivity to treatment-
related changes [141, 143, 145]. The parent RCADS has not been included in any anxiety clinical
trials to date.
Clinician Rating Scales
Clinician rating scales are useful as a supplement to child and parent rating scales, especially given
research showing response biases in child and parent reports [7]. The only clinician rating scale
specific to pediatric anxiety disorders is the Pediatric Anxiety Rating Scale (PARS) [146].
The PARS contains a 50-item symptom checklist and 7 severity items that assess frequency, severity,
and impairment related to symptoms of DSM-IV SAD, SOP, and GAD in children ages 6–17 years.
The PARS is administered by interviewing the child and parent separately or together. The PARS
symptom checklist contains six subscales: Separation, Social Interactions or Performance Situations,
Generalized, Specific Phobia, Physical Signs and Symptoms, and Other Symptoms. Each symptom is
rated by the clinician as present/absent based on the “yes” or “no” responses elicited from the child,
parent, or both. There appears to be an inconsistency across studies, or information is vague on the
source upon which clinicians’ PARS ratings were obtained.
Integrating information obtained from both children and parents, clinicians then rate the severity
of the anxiety symptoms endorsed as presented by the child and/or parent along seven dimensions
using a 6-point scale (0 for none and 1–5 for minimal to extreme) for each dimension. The seven
dimensions include number of symptoms, frequency, severity of distress associated with anxiety
symptoms, interference at home, severity of physical symptoms, and avoidance. Scores of 3 or greater
on each dimension indicate clinically significant severity, avoidance, or interference. A total score is
also calculated by summing five of the seven dimensions (not including number of symptoms and
severity of physical symptoms). Higher scores indicate higher severity of anxiety symptoms.
The reliability and validity of the PARS have been evaluated [146, 147]. Internal consistency alpha
coefficients for the PARS total score have varied, with alphas ranging from 0.64 to 0.91 across studies
[146, 147]. Modest test–retest reliability estimates (24-day interval) have been reported for the total
score and dimensional scales (ICCs: 0.35–0.59) [146]. However, excellent interrater reliability esti-
mates have been reported for the total score and dimensional scales (ICCs: 0.78–0.97) [146].
The PARS has support for convergent validity in that significant correlations have been found
between the PARS and clinician rating scales, such as the Clinician Global Impressions (Severity
Scale) [49] and the Hamilton Anxiety Rating Scale [148] (rs: 0.49–0.61). The PARS has support for
divergent validity in that low or nonsignificant correlations have been found between the PARS and a
clinician rating scale of depressive symptoms (rs: 0.18–0.33) [146, 147]. ROC analyses have indi-
cated that the PARS total score has high accuracy in identifying children with anxiety disorders
(AUC = 1.00), with a cutoff score of 11.5 resulting in a sensitivity rate of 100 % and specificity rate of
98.8 % [147]. The PARS also has been found to be sensitive to treatment change. Specifically, change
in the PARS total score has been found to be significantly correlated with pre- to posttreatment changes
in global clinician rating scales (rs: 0.41–0.78) [146].
Global Psychopathology Scales
In addition to child and parent anxiety rating scales, there are a few rating scales designed to assess a
broad range of symptoms in children, including anxiety symptoms. These include the Achenbach
System of Empirically Based Assessment (ASEBA) for School-Age Children [88] and the Behavior
Assessment Scale for Children (second edition) (BASC-2) [149]. Both scales have a long history in the
pediatric assessment area; however, the ASEBA scales are more widely used in the area of pediatric
anxiety. Both the ASEBA and BASC-2 contain child, parent, and teacher versions. Below we sum-
marize both of these rating scales. We also summarize the available reliability, validity, and utility
information of the scales, with an emphasis on the anxiety subscales.
The ASEBA scales are designed to assess competencies, adaptive functioning, and problem behav-
iors in children and adolescents. The ASEBA scales include the Child Behavior Checklist (CBCL),
Youth Self-Report (YSR), and Teacher Report Form (TRF). Both CBCL and TRF are administered to
parents and teachers, respectively, of children ages 6–18 years old, and the YSR is administered to
children ages 11–18 years old. The ASEBA scales contain 118 items that assess a range of problem
behaviors. Respondents rate the frequency of each problem behavior (e.g., “too fearful or anxious,”
252 Y. Rey et al.
“temper tantrums,” and “cries a lot”) using a 3-point scale (not true, somewhat or sometimes true, very
true or often true). The majority of the problem behavior items are the same across the ASEBA scales
(CBCL, YSR, TRF), though there are a few differences (e.g., YSR contains items that assess social
desirability that are not included in the CBCL or TRF).
In addition to the Total Problems scale, ASEBA scales (i.e., CBCL, YSR, TRF) contain two
broadband and eight narrowband subscales. The Internalizing broadband subscale and the Anxious/
Depressed narrowband subscale include items that assess anxiety symptoms in children. The CBCL’s
Internalizing and Anxious/Depressed subscales in particular have been used in most of the pediatric
anxiety clinical trials and are sensitive to treatment change (see Silverman and Ollendick) [7].
Recently, six DSM-Oriented subscales were included in the ASEBA scales to provide a closer link
with the DSM-IV [150]. The DSM Anxiety Problems subscale specifically assesses for symptoms of
DSM-IV GAD, SAD, and SP, though it has been rarely used in the clinical child anxiety literature.
The ASEBA scales were standardized using a national US probability sample of children. Norms are
available for the CBCL and TRF separately by sex and age (6–11 years and 12–18 years), and norms
are available by sex for the YSR. A T-score of 64 or higher on the broadband subscales (e.g.,
Internalizing) and a T-score of 70 or higher on the narrowband (e.g., Anxious/Depressed) and DSM-
Oriented subscales (e.g., Anxiety Problems) are considered clinically significant [88].
The BASC-2 [149] is designed to assess adaptive and clinical dimensions of behavior in children.
It includes parent rating scales (PRS), teacher rating scales (TRS), and a self-report of personality
(SRP). The PRS and TRS have specific versions to assess children across three age ranges: 2–5 years
old, 6–11 years old, and 12–21 years old. Each version of the PRS contains 160 items and each ver-
sion of the TRS contains 139 items. The SRP contains 185 items and is administered to children ages
6 through 25 years. Respondents rate the frequency of behaviors using a four-point scale (from “never”
to “almost always”). All of the BASC-2 scales (i.e., PRS, TRS, SRP) include a number of clinical
subscales, including an anxiety subscale. Norms based on a nationally representative sample of children
are available for the BASC scales separately by sex, age, and clinical status. A T-score of 70 or higher
on the clinical subscales (e.g., Anxiety subscale) falls in the clinical range [149].
Reliability
Alpha coefficients for the ASEBA Internalizing, Anxious/Depressed, and DSM Anxiety Problems
subscales range from 0.72 to 0.90 [88, 151], though an alpha of 0.67 was reported for the DSM
Anxiety Problems subscale of the YSR [88]. Alpha coefficients for the BASC clinical subscales (includ-
ing the Anxiety subscale) are above 0.80 [149].
Retest reliability (r) estimates for the Internalizing, Anxious Depressed, and Anxiety Problems
subscales range from 0.68 to 0.91 for the CBCL and YSR over an 8-day retest interval and from 0.73
to 0.86 for the TRF over a 16-day retest interval [88, 151]. Retest reliability (r) estimates for the
BASC clinical subscales (including the Anxiety subscale) are above 0.70 [149].
Validity
The ASEBA Internalizing, Anxious/Depressed, and DSM Anxiety Problems subscales have evidence
for convergent validity with other related measures. For example, the CBCL and TRF Internalizing,
Anxious/Depressed, and Anxiety Problems subscales have demonstrated significant correlations (r)
with respective parent and teacher ratings on the BASC Anxiety subscales (rs: 0.46–0.83), thus sup-
porting the convergent validity of the BASC as well [88]. The YSR Anxious/Depressed and DSM
Anxiety Problems subscales also have demonstrated significant correlations with the anxiety subscales
of the RCADS (rs: 0.49–0.59) [152].
Information on discriminant validity of the Internalizing, Anxious/Depressed, and DSM Anxiety

Problems subscales is available only for the CBCL. The CBCL Internalizing subscale has been found
to discriminate between children with anxiety disorders and those with externalizing disorders, but
not children with depressive disorders [135]. The CBCL Anxious/Depressed subscale has been found
to discriminate between children diagnosed with specific anxiety disorders (i.e., SAD, GAD, SP)
from children without these disorders and from children with depressive disorders [153]. The CBCL
DSM Anxiety Problems scale also has been found to discriminate children with specific anxiety dis-
orders (i.e., PD, SAD, SOP, PTSD, GAD, SP, OCD) from those without anxiety disorders and those
with depressive disorders [151, 153]. Information on the discriminant validity of the BASC Anxiety
subscales is not available.
Screening
Information on the screening utility of the Internalizing, Anxious/Depressed, and DSM Anxiety
Problems subscales is only available for the CBCL and YSR. In terms of the CBCL, Aschenbrand
et al. [154] used ROC analyses in a sample of parents of anxious and non-anxious children and found
that CBCL Internalizing and Anxious/Depressed subscales had moderate to good accuracy (AUCs:
0.84–0.94) for screening children with any anxiety disorder (i.e., SAD, SOP, GAD) but low to moder-
ate accuracy for screening children specifically for GAD (AUCs: 0.65–0.73) and SOP (AUCs: 0.40–
0.44). The CBCL DSM Anxiety Problems subscale was found to have low accuracy for screening
children with any anxiety disorder as well as children with specific anxiety disorders (SAD, GAD,
and SP) from those without these anxiety disorders (AUCs: 0.60–0.70) in a sample of parents of
clinic-referred children [155].
In a recent study using a sample of parents of clinic-referred children, Ebesutani et al. [153]
found the CBCL Anxious/Depressed and DSM Anxiety Problems subscales had moderate accuracy
for identifying children with SAD, GAD, and SP, respectively, from children without these disor-
ders and from children with depressive disorders (AUCs: 0.72–0.84). Comparisons of the two sub-
scales also revealed the Anxiety Problems subscale (AUCs: 0.82–0.84) yielded significantly greater
AUC values than the Anxious/Depressed subscale (AUCs: 0.72–0.80). Thus, the Anxiety Problems
subscale fares better than the Anxious/Depressed scale for screening children with anxiety disor-
ders from children with depressive disorders. However, one study using the YSR in a sample of
children referred to an anxiety and depression clinic [155] found that both the Anxious/Depressed
and Anxiety Problems subscales had low accuracy in identifying children with any anxiety diagno-
sis (AUCs: 0.64–0.68). Information on the screening utility of the BASC Anxiety subscales is
unavailable.
Summary
Overall, there are a number of widely used dimensional rating scales available for the assessment of
pediatric anxiety. Additionally, global psychopathology rating scales commonly used in clinical child
assessment contain subscales used to assess pediatric anxiety. The rating scales summarized possess
adequate evidence with respect to internal consistency and retest reliability, though retest reliability
estimates are lacking for the parent SCARED and SCAS. Most of the rating scales also show evidence
for convergent validity with other anxiety scales. However, most anxiety rating scales have shown
strong convergence with measures of depression, providing only partial support for the divergent
validity of the scales. More work is needed on the convergent and divergent validity of the parent
SCARED and the divergent validity of the parent MASC.
254 Y. Rey et al.
With respect to discriminating between anxiety and other clinical disorders, the child and parent
SCARED and MASC are recommended. The child and parent SCARED, MASC, and SCAS sub-
scales, as well as the child and parent RCADS anxiety subscales, are useful for discriminating
among specific anxiety disorders. However, caution is warranted when using some of the subscales
of the child MASC and SCARED. In terms of screening utility, the majority of the rating scales
summarized (except the PARS) have low to moderate accuracy in identifying children with anxiety
disorders. Therefore, when screening children for anxiety disorders, it is recommended that clini-
cians not rely solely on rating scales and include other methods of assessment, such as a diagnostic
interview schedule.
Preschool Assessment
All of the categorical and dimensional measures summarized thus far are applicable for assessing
children of school age (6–18 years old). In recent years, there has been growing recognition that anxi-
ety is prevalent in children of preschool age [156, 157]. For example, in community samples of pre-
school children, a prevalence rate of 9.4 % was reported for the presence of “any anxiety disorder”
[156]. Therefore, identification of anxiety at this young age is important for treatment and prevention
of later difficulties [158].
There are only a few evidence-based instruments designed specifically for the assessment of anxi-
ety in preschool children. All are completed by parents and/or teachers, because the reliability of
young children’s self-reports of anxiety is suspect [24]. The Preschool Age Psychiatric Assessment
(PAPA) [159, 160] is an interview schedule that covers a number of disorders, including anxiety dis-
orders in preschool children. The Preschool Anxiety Scale (PAS) [161] is a rating scale designed
specifically for assessing anxiety in preschool children. There are two other rating scales that assess a
broad range of symptoms in preschool-age children that contain subscales for assessing anxiety: the
Children’s Moods, Fears and Worries Questionnaire (CMFWQ) [162] and the ASEBA Scales for
Preschool Age Children [163]. As indicated earlier, the BASC-2 TRS and PRS also include versions
to assess children ages 2–5 years [149].
The PAPA [159, 160] is a parent semi-structured interview based on the parent version of the
CAPA [34, 35]. The PAPA is similar to the CAPA, but some of the content and structure has been
revised to improve its utility with preschool-age children (2–5 years old). The PAPA assesses fre-
quency, intensity, and duration of symptoms of 16 psychiatric disorders, including anxiety, based on
several classification systems (i.e., DSM-IV-TR, ICD-10, RDC-Preschool Age [RDC-PA] [158], and
Diagnostic Criteria: Zero to Three [164]). Additional symptoms and behaviors commonly exhibited by
young children are assessed (e.g., sleep and eating behaviors, toileting history). Impairment ratings can
also be obtained in 30 areas, such as the child’s relationships with others (i.e., parents, other adults,
siblings, peers), as well as the child’s functioning at home, school or daycare, and out of home.
Only one study has examined the reliability of the PAPA. Egger et al. [160] examined the test–
retest reliability of a number of psychiatric disorders (including anxiety disorders) using the PAPA in
a sample of parents of preschoolers (2–5 years old) recruited from a pediatric clinic. Findings showed
reliability estimates were poor for GAD (k[kappa] = 0.39) and SP (k[kappa] = 0.36), fair for SOP
(k[kappa] = 0.54), good for SAD (k[kappa] = 0.60), and excellent for PTSD (k[kappa] = 0.73). No
studies have evaluated the validity of diagnoses using the PAPA.
The PAS [161] is a 28-item parent-report rating scale designed specifically to assess a range of
anxiety symptoms based on the DSM-IV in preschool-age children (2–6 years old). Parents rate the
frequency of their child’s experiences such as “is afraid of the dark” and “is afraid of meeting or talk-
ing to unfamiliar people” using a 5-point scale (from not true at all to very often true). In addition to
the Total score, the PAS contains five subscales: Separation Anxiety, Generalized Anxiety, Social
Anxiety, Obsessive-Compulsive, and Physical Injury Fears. Recently, the PAS was revised (PAS-R)
[165] to a 30-item version to better reflect the range of common symptoms of anxiety in this age group
as well as to provide a clear distinction between the Separation Anxiety and Generalized Anxiety
subscales. Norms for the original PAS based on an Australian community sample (N = 510) of moth-
ers of preschool-age children are available separately by sex and each age (3–5 years old). A T-score
of 60 or higher on the PAS total or subscales indicates clinically significant levels of anxiety.
In terms of internal consistency, alpha (a) coefficients for the PAS and PAS-R total scores are
above 0.80. Alpha coefficients for the PAS Generalized Anxiety and Social Anxiety scales are above
0.75, though alphas lower than 0.70 have been reported for the Separation Anxiety, Physical Injury
Fears, and Obsessive-Compulsive subscales (a: 0.59–0.66) [166]. All the PAS-R subscales, however,
yielded alphas over 0.70 (a: 0.72–0.89) [165]. Retest reliability estimates (over 12 month interval) for
the PAS-R total and subscale scores are large in magnitude (rs: 0.60–0.76) [165].
The PAS and PAS-R evidence convergent validity in that the total scales and subscales correlate
significantly with other parent rating scales (i.e., CBCL Internalizing subscale, CMFWQ, and
Emotional Symptoms subscale of the Strengths and Difficulties questionnaire [167]) (rs: 0.50–0.77)
[161, 165, 166]. However, the Obsessive-Compulsive and Physical Injury Fears subscales have yielded
relatively lower correlations with parent rating scales of anxiety (rs: 0.35–0.49) compared to the other
PAS/PAS-R subscales [161, 165, 166].
The PAS/PAS-R also exhibits adequate divergent validity in that the total scale and subscales have
yielded low or nonsignificant correlations with parent measures of externalizing symptoms (i.e.,
CBCL Externalizing scale, SDQ Conduct Problems scale, SDQ Hyperactive Inattention scale)
(rs: −0.01 to 0.28) [161, 165]. In terms of discriminative validity, the total score of the PAS-R can
discriminate between children (ages 3–5 years old) with anxiety diagnoses from children without
diagnoses, and the subscales (except Obsessive-Compulsive) can discriminate between children with
specific anxiety diagnoses corresponding to the subscales from children without these respective
diagnoses [165].
The CMFWQ [162] is a 60-item parent-report rating scale specifically designed to assess a broad
range of internalizing symptoms, including anxiety, in children ages 2–6 years old. Parents rate the
frequency of their child’s experiences such as “Fears strangers” and “Looks sad, miserable, and
unhappy” using a 5-point scale (from almost never to almost always). In addition to the Total score,
the CMFWQ contains three subscales: Anxiety Problems, Inhibition/Solitary Play, and Mood
Problems. Currently, there are no norms available for the CMFWQ. Internal consistency (a)
coefficients for the CMFWQ total score and subscales are above 0.80 [162, 166]. Retest reliability (r)
estimate (over 2-year interval) for the total scale is 0.56 [162]. The CMFWQ total scale and subscales
correlate significantly with a parent rating scale of temperament (i.e., Short Temperament Scale for
Toddlers [168]) (r = 0.42) and with the PAS total score (rs: 0.56–0.75) [166].
In addition to the scales for school-age children, the ASEBA contains scales for preschool-age
children [163]. The ASEBA preschool scales include the CBCL for ages 1½–5 years (CBCL/1½ –5)
and the Caregiver-Teacher Report Form (C-TRF). The ASEBA scales for preschool-age children are
similar to the school-age scales in content and structure, and respondents rate the frequency of each
problem behavior using a 3-point scale (not true, somewhat or sometimes true, very true or often
true), similar to the school-age forms.
The ASEBA preschool scales (i.e., CBCL/1½–5, C-TRF) include the same broadband, narrow-
band, and DSM-Oriented scales found in the school-age forms, though three subscales are included
in the preschool scales that are not included in the school-age scales (i.e., Emotionally Reactive, Sleep
Problems, and DSM-Oriented Pervasive Developmental Problems subscales). Norms based on a
nationally representative US sample are available for the CBCL/1½–5 and C-TRF separately by sex.
A T-score of 64 or higher on the Internalizing and Externalizing broadband scales and a T-score of 70
or higher on the narrowband (e.g., Anxious/Depressed) and DSM-Oriented subscales (e.g., Anxiety
Problems) are viewed as being clinically significant [163].
256 Y. Rey et al.
The reliability estimates for the ASEBA preschool scales are similar to those obtained for the
school-age forms. Alpha coefficients for the CBCL/1½–5 and C-TRF Internalizing, Anxious/
Depressed, and Anxiety Problems subscales scores are above 0.70. Retest reliability (r) estimates
(over an 8-day interval) for these subscales are above 0.50 [163]. Less information is available regard-
ing the validity of the Internalizing, Anxious/Depressed, and DSM Anxiety Problems subscales of the
ASEBA preschool scales although the available research supports the validity of the CBCL Internalizing
subscale and the CBCL and C-TRF Anxious/Depressed subscale. For example, the CBCL/1½–5
Internalizing subscale has evidence of convergent validity with the Internalizing subscales of the
Infant-Toddler Social Emotional Assessment [169] (rs: 0.48 and 0.62). The Internalizing and Anxious/
Depressed subscales of the CBCL and C-TRF also discriminate between non-referred and referred
children [163]. More research is needed to evaluate the validity of DSM Anxiety Problems subscale.
In summary, there are only a few instruments available for the assessment of pediatric anxiety in
preschool children. The PAPA is the only interview schedule designed specifically to diagnose psychi-
atric disorders in preschool children. Reliability estimates obtained for some anxiety disorders have
been poor to modest, and information on the validity of the anxiety diagnoses is needed. The PAS/
PAS-R, CMFWQ, and ASEBA preschool scales possess sufficient and adequate evidence with respect
to internal consistency and retest reliability. The PAS and CMFWQ also have evidence of convergent
and divergent validity, but only the PAS has evidence for discriminant validity. More research also is
needed on the validity of the Internalizing, Anxious/Depressed, and DSM Anxiety Problems sub-
scales of the ASEBA preschool scales.
Objective Measures
Interview schedules and rating scales have been emphasized in this chapter because they are the most
widely used and researched categorical and dimensional assessment approaches for pediatric anxiety.
As noted, however, interviews and rating scales do not capture directly the two additional aspects of
anxiety: avoidance of anxiety-provoking situations or objects and physiological reactions. Direct
behavioral observations and psychophysiological measures more directly capture these aspects. These
are each briefly discussed below.
Direct Observations
Direct observational tasks have been used to identify and quantify specific avoidant behaviors in anxious
children [170–172]. They also have been used to assess subjective levels of anxiety, based on child
and/or observer ratings, while the child is in the anxiety-provoking situations (e.g., reading aloud to a
group) [173–175]. These tasks have served as outcome measures in several pediatric anxiety clinical
trials, with varied findings [171–175].
The two most widely used types of direct observation tasks have been behavior avoidance tasks
(BATs) and social evaluative tasks. In BATs, children are typically asked to approach a feared object or
situation in a series of graded steps (varying between 8 and 27) [171, 172]. Trained observers then record
the number of steps taken by the child as he/she approached the feared stimulus. Children also are asked
to rate their level of fear or anxiety during the BAT. In social evaluative observation tasks, children
(usually those with SOP) are typically asked to role play with a peer, read aloud a story in front of a
small group, or talk about themselves to a small group. Children, and often trained observers, provide
ratings of anxiety. Children’s performance of the task has also been rated in some studies [173–175].
Reliability of direct observation tasks has been evaluated. Studies that have used social evaluative
tasks, for example, in samples of children with SOP, have reported large interrater reliability estimates
for the observers’ ratings of the child’s anxiety levels (rs: 0.82 and 0.87), as well as the child’s
performance during the tasks (r = 0.89) [173–175]. Studies that have used BATs in samples of
children with specific phobias reported large retest reliability estimates for number of steps achieved
(r = 0.97 over 1 week; r = 0.92 over 1 h) and for children’s anxiety levels during the BAT (r = 0.87 over
1 h) [170, 171]. Currently, there is no information regarding the validity of direct observations for
assessment of pediatric anxiety. For example, no studies evaluate whether direct observations can
discriminate children with anxiety disorders from children without anxiety disorders, as well as among
the different anxiety disorders.
Presence of observers may potentially influence how children behave [176]. It is therefore important
to have some time to allow children to habituate to the observers’ presence [176]. Another limitation of
direct observations is the absence of a standardized approach for conducting such observations, as well
as their coding. As a consequence, it is difficult to generalize findings across studies [177]. Despite these
limitations, direct observation tasks are useful for directly capturing the extent of children’s avoidance
of anxiety-provoking stimuli as well as children’s level of anxiety while performing the tasks.
Physiological Measures
Although physiological measures provide the most direct and unbiased way to capture fear or anxiety
responses, such measures are used less frequently in the assessment of pediatric anxiety relative to the
other assessment measures discussed in this chapter [178]. In general, physiological assessment of
anxiety focuses on two systems: the sympathetic adrenal medullary (SAM) system and hypothalamic
pituitary adrenal (HPA) axis [179].
The SAM system relies on indices of heart rate (HR) and blood pressure (BP) and, to a lesser
extent, galvanic skin response (GSR). There is scant research on the psychometric properties and
clinical utility of these measures in samples of anxious children. Few studies have examined the reli-
ability of physiological measures using retest intervals of varying lengths (e.g., 2 weeks, 60 s). Beidel
et al. [180], for example, reported 2-week retest reliability estimates that were moderate to large for
BP (rs: 0.29–0.64) and weak to moderate for HR (rs: 0.15–0.48), both measured before and during
two 10-min behavior tasks (vocabulary test, read-aloud task) in children with SOP and non-anxious
children. Also of interest in the Beidel et al. study [180] was the stability of BP and HR over time.
Findings showed that 6-month stability estimates were weak to large for BP (rs: 0.04–0.63) and weak
to moderate for HR (rs: 0.19–0.22).
Weems et al. [181] examined retest reliability of HR and GSR over a 60 s interval in a community
sample of children (6–17 years old) exposed to a video of a mildly phobic stimulus (i.e., large dog
running toward the camera). HR and GSR were measured at several time points: after children viewed
a blank screen for 10 s, after viewing an initial video (i.e., a pastoral scene for habituation) prior to the
video of the phobic stimulus, and after viewing the video of the phobic stimulus. Large retest reli-
ability estimates were reported for HR and GSR (rs: 0.71 and 0.97, respectively) between the initial
blank screen and pre-video period.
In terms of discriminant validity, Beidel [182] found HR discriminated between children with test
anxiety from children with no anxiety during two behavior tasks (vocabulary test and read-aloud
task). BP however did not discriminate between these two groups of children. Using a community
sample of adolescents (13–17 years), Anderson and Hope [183] found that neither HR nor BP dis-
criminated between adolescents with SOP from adolescents without a diagnosis during two 10-min
anxiety-provoking behavior tasks (i.e., speech task and conversation with an unfamiliar person).
Additionally, in the Weems et al. [181] study mentioned above, HR discriminated children with high
levels of anxiety from those with low levels of anxiety during and after exposure to the mildly phobic
stimulus. GSR, however, did not discriminate between these groups of children. In addition, change
in HR, but not in GSR, before and after watching the video was more strongly associated with anxiety
258 Y. Rey et al.
than depressive symptoms according to child report. Given the failure to find BP and GSR could
discriminate between children with anxiety and children without anxiety, further research is needed
on these measures before they are used for such purposes. HR has somewhat better evidence for dis-
criminant validity, though findings are inconsistent. More research is needed here too.
Only one pediatric anxiety trial has examined the sensitivity of physiological measures to treat-
ment change. Specifically, Ost et al. [172] examined a one-session treatment for various phobias and
measured the BP and HR at the highest step they attained on a BAT at pre- and posttreatment. BP was
found to be significantly lower at posttreatment than at pretreatment for children assigned to active
treatment conditions versus a waitlist. HR, however, did not show sensitivity to treatment change.
Research studies conducted on physiological indices of the HPA system in pediatric anxiety are
even scarcer than studies conducted on indices of the SAM system. HPA activity is usually assessed
via cortisol levels in the blood, urine, or saliva or measurement of adrenocorticotropic hormone [179].
Most of the research on HPA activity has been conducted in samples of children with depression or
disruptive disorders [184, 185]. In samples of anxious children, the few studies conducted have found
increased basal cortisol activity among children with PTSD compared to non-anxious children [186]
and among clinic-referred children with SOP [187, 188]. Here too, more research is needed to deter-
mine psychometric properties and clinical utility.
Summary
This section summarized briefly the information available using direct observations and physiological
measures with anxious children. Compared to interview schedules and rating scales, objective
measures are not as widely used or studied. Direct observational tasks have been used primarily to
quantify avoidant behaviors, obtain subjective ratings of anxiety during the task, and evaluate treat-
ment outcome. There is some information on the reliability of direct observations for assessing pedi-
atric anxiety, but information on validity is lacking. Furthermore, reactivity of children during
observation tasks may influence the external validity of the findings. There also are currently no stan-
dardized tasks and coding procedures, thus making it difficult to generalize across studies [177].
Physiological measurements aid in directly capturing physiological reactions of anxiety in chil-
dren, but they have been insufficiently studied in the pediatric anxiety assessment area. Few studies
have examined the reliability of physiological measures and have used retest intervals of varying
lengths in the anxiety area, making it difficult to draw conclusions about the reliability of such mea-
sures for this problem area. Further, studies have not found support for discriminant validity of BP and
GSR. Although there is some support for the discriminant validity of HR, findings are inconsistent. As
noted, further research is needed on physiological measurement in pediatric anxiety before they can
be recommended for clinical purposes.
Clinical Considerations
In pediatric anxiety treatment research, it is common practice to administer a full assessment battery
to the patients and their parents, which includes an interview schedule, several rating scales, and in
some cases direct observation tasks and physiological measures at pre- and posttreatment and during
follow-up periods. However, this is not often the case in clinical practice, where such a comprehensive
assessment is rarely feasible. In choosing which assessment instruments would be most practical for
use in clinical settings, factors such as cost, time, and training must be considered.
Most interview schedules used to diagnose pediatric anxiety disorders need to be purchased (with
the exception of the K-SADS which is freely available). Interview schedules are also lengthy, taking
anywhere between 90 and 120 min to administer per informant. However, clinicians have the flexibility
of using the interview schedules as templates that can guide their questioning rather than a script that
must be precisely followed [189]. By using the interview schedules this way, the interviewer has
available a full range of empirically validated DSM-based questions to which he or she can refer.
Rating scales such as the RCADS, SCAS, and SCARED are freely available, while the MASC,
RCMAS, STAIC, CBCL, and BASC-2 need to be purchased. Administration time for rating scales is
minimal, taking between 5 and 20 min to complete. Training required for most rating scales also is
minimal. Direct observations and physiological assessment of anxiety are costly, lengthy, and require
extensive training and extra staff members available for administration, thus making them less feasi-
ble for use in clinical practice settings.
Future Research Directions
There remains a need for further research that cuts across categorical and dimensional perspectives.
First, as previously mentioned, the advent of the DSM 5 will likely have implications for existing
categorical and dimensional measures of pediatric anxiety disorders that may require revision and
further psychometric assessment.
Second, another revision to the DSM that will likely have implications for the assessment of pedi-
atric anxiety is the inclusion of dimensional severity ratings to the diagnostic categories of the upcom-
ing DSM 5. Dimensional severity ratings would allow clinicians to rate both the presence and severity
of symptoms (e.g., “very severe,” “severe,” “moderate,” or “mild”) [190]. Inclusion of dimensional
severity ratings may address some of the limitations of a categorical approach. These include the
DSM’s inability to capture individual differences in severity of a given disorder and inability to pro-
vide information about severity of subthreshold symptoms [191, 192]. Research on whether including
dimensional severity ratings successfully addresses these disadvantages will be needed.
Third, the instruments summarized in this chapter were originally developed in English and tested
with predominantly Caucasian children. It is unclear whether these instruments are applicable for
assessing anxiety disorders in children from diverse backgrounds. Some of the categorical and dimen-
sional instruments summarized in this chapter do show promise for such use, at least in terms of simi-
lar reliability and validity estimates (e.g., Ólason et al. [72] and Mellon and Moutavelis [105]). More
research is needed, however, especially on the issue of measurement equivalence—whether these
instruments assess anxiety in the same way across diverse groups of children [193]. See Pina et al.
[194] as an example of a measurement equivalence study, which showed the RCMAS yields equiva-
lent information across European American and Latino children diagnosed with anxiety disorders.
In closing, as this chapter has illustrated, researchers and clinicians have available a number of
sound measures, based on categorical and dimensional perspectives to assess pediatric anxiety. We
hope the chapter will help guide decisions about “which measure to use for which purpose” and at the
same time allow for continued advancements in our understanding of pediatric anxiety disorders from
both categorical and dimensional perspectives.
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Cognitive–Behavioral Treatment for Pediatric
Anxiety Disorders
Kendra L. Read, Connor M. Puleo, Chiaying Wei, Colleen M. Cummings,

and Philip C. Kendall
Abstract Anxiety disorders are among the most prevalent and debilitating psychological disorders
among children and adolescents. Cognitive–behavioral treatments (CBTs) for anxiety disorders
are linked to a tripartite model of anxiety and address cognition (anticipated threat), behavior
(avoidance), and emotions (agitated arousal). Empirical evidence supports the use of cognitive–
behavioral interventions as efficacious treatment for many anxiety disorders in youth, including gen-
eralized anxiety disorder (GAD), separation anxiety disorder (SAD), social phobia (SP),
obsessive–compulsive disorder (OCD), and post-traumatic stress disorder (PTSD). Along with
descriptions of CBT, a number of recommendations are made for future work.
Keywords Anxiety • Treatment • Children • Adolescents • Cognitive–behavioral treatment
Anxiety disorders are among the most common psychological disorders affecting children and ado-
lescents [1], with prevalence rates reported between 10 % and 20 % [2–4]. If left untreated, pediatric
anxiety disorders can lead to impairment in socioemotional functioning across the lifespan, including
high rates of other mental health disorders, such as substance use [5, 6]. Substantial consequences in
academic, vocational, and interpersonal performance are also prevalent [4, 7, 8]. As such, anxiety
disorders represent an important target in the development of evidence-based interventions for chil-
dren and adolescents. According to The Association for Behavioral and Cognitive Therapies and the
Society for Clinical Child and Adolescent Psychology [9], cognitive–behavioral interventions are
the most highly recommended treatments for anxiety disorders in youth, described as either “well-
established” or “probably efficacious” based on current research.
This chapter describes the theoretical basis and main components of cognitive–behavioral treat-
ment (CBT) for anxiety disorders broadly and then reviews empirically supported treatments (ESTs)
for specific disorders, including generalized anxiety disorder (GAD), separation anxiety disorder
(SAD), social phobia (SP), obsessive–compulsive disorder (OCD), and post-traumatic stress disorder
(PTSD). It will also review recent efforts to address issues of effectiveness in community settings and
novel treatment approaches (e.g., computer-based delivery).
K.L. Read (*) • C.M. Puleo • C. Wei • C.M. Cummings • P.C. Kendall
Department of Psychology, Temple University, Philadelphia, PA, USA
e-mail: kendra.read@temple.edu
270 K.L. Read et al.
A Tripartite Model of Anxiety
Anxiety-focused cognitive–behavioral interventions are based on a tripartite model of anxiety, which

proposes that anxiety results from the interaction of thoughts, emotions/physiological responses, and
behaviors [10]. Elevated emotional responses and accompanying physiological arousal experienced
by anxious children are linked to both cognitive distortion (e.g., exaggerated estimates of threat) and
behavioral avoidance that keeps the anxious child from encountering, facing, and eventually master-
ing feared situations [11]. CBT for anxiety disorders helps children (1) identify and challenge anxious
cognitions, (2) cope with and regulate anxious feelings and physiological responses to anxiety, and
(3) unlearn patterns of behavioral avoidance in the face of anxiety-provoking situations or stimuli.
CBT Components
Although treatments for specific disorders may differ, most contain the following components: (1)
psychoeducation, (2) relaxation/somatic management, (3) cognitive restructuring, (4) problem solv-
ing, (5) exposure tasks, and (6) relapse prevention. Treatment components are often delivered in this
order, but much flexibility is needed to tailor the treatment to the child’s needs and particular anxiety
disorder. Overall, these components of CBT for child anxiety, described in detail below, are recom-
mended to be delivered in a fun, flexible, and collaborative format that allows the child to be an inte-
gral player in the treatment of his/her anxiety.
Psychoeducation
Psychoeducation has been shown to be an important component of treatment and preventive interven-
tions [12]. Essentially, the therapist provides information about anxiety and the CBT model to the
youth and his/her family. This information helps the child identify triggers of anxiety in his/her body
and the environment, addresses expectations about treatment, and provides a sense of knowledge
about the course of therapy for the coming weeks. The therapist describes anxiety as an adaptive
response that, for children with anxiety disorders, can become out of proportion in its reaction to the
environment. For some children, it may be useful to use a metaphor, like an overly sensitive safety
alarm that goes off when no danger is present. With OCD, therapists may refer to obsessions as “brain
hiccups,” for which one might attribute incorrect techniques to alleviate the hiccups (i.e., compul-
sions). The therapist dispels the common belief that therapy will eliminate anxiety and instead dis-
cusses how therapy will help the child to learn needed strategies to cope with anxiety. The therapist
normalizes the experience of anxiety for the child, sometimes by sharing how s/he has coped with an
anxiety-provoking experience.
Orienting the child and his/her parents to therapy includes discussion of anxiety symptoms and
their manifestation. Providing this information to the child can help him/her recognize the early
signs of anxiety in his/her body and how to differentiate these signs from somatic problems.
Research suggests that anxious children may show deficits in recognizing the emotional states of
self and others [13], and psychoeducation addresses these deficits by providing youth with a vocab-
ulary to understand emotions in general and anxiety specifically. Further, by establishing connec-
tions between thoughts and actions and feelings, the therapist may discuss multiple avenues for
regulating unwanted anxiety through treatment, for example, by altering self-talk (cognition) and
experience (behavior).
Cognitive–Behavioral Treatment for Pediatric Anxiety Disorders 271
Overall, the psychoeducation component offers the child with useful information, builds a
collaborative relationship between therapist and child, and provides hope and confidence that the
overwhelming anxiety s/he currently feels can ultimately be managed.
Relaxation/Somatic Management
Relaxation strategies, such as progressive muscle relaxation and deep breathing, though potentially
effective when used alone [14, 15], may be combined with cognitive coping strategies in CBT pro-
grams for anxiety to help children identify and regulate the physiological arousal that often accompa-
nies anxious or negative emotionality [16–18]. Thus, the goal of these strategies is to provide methods
of gaining control over unwanted anxious (physiological) arousal. During progressive muscle relax-
ation, children learn to flex and relax specific muscle groups in succession to promote relaxation and
increase awareness of physiological tension as an indicator of anxiety. Deep breathing involves taking
deep diaphragmatic breaths, in contrast to quick and short breaths, which are likely reminiscent of
anxious arousal responses.
The therapist uses a developmentally appropriate approach to introduce the rationale behind relax-
ation, as it might not always be evident to children [19], and to teach the skills. When introducing
these strategies to children, the therapist may use a salient metaphor (e.g., squeezing lemons, blowing
up a balloon in one’s belly) to illustrate the procedures. The child is encouraged to choose which
relaxation strategy they want to use. For younger children, the therapist may participate in the relax-
ation procedures along with the client. For older children and adolescents, the therapist may face
away from the teenager to allow them to relax without feeling self-conscious. Therapists can use
prerecorded scripts or recordings of the relaxation techniques to allow the therapist to participate and
to facilitate use of strategies at home. It is important to note that not all CBT treatments emphasize a
need to address relaxation (i.e., CBT-ERP for OCD, see below), illustrating the differential applica-
tion of these components for particular disorders.
Reduction in negative self-talk is a significant mediator of change in treatment outcome studies for
child anxiety [20]. Thus, the cognitive restructuring component of treatment is an important one. One
goal of this component is to introduce “self-talk” (thoughts) as a way to address the cognitive compo-
nent of pediatric anxiety. The therapist introduces the premise that changing patterns of automatic
self-talk can, in turn, provide a pathway to alter emotions and behavior. Conceptually, self-talk can be
introduced to children as communication with oneself that can be either “helpful” or “interfering,”
depending on its effects on emotions and behavior. In anxious youth, this self-talk often takes the form
of a cognitive distortion about the presence and likelihood of environmental threat (e.g., “If I give a
speech, everyone will laugh at me” or “I will get sick if I do not wash my hands repeatedly”).
Understanding self-talk allows the child to recognize patterns of negative thoughts, called “thinking
traps” (e.g., all-or-nothing thinking, faulty attributions, catastrophic outcomes), and to challenge and
restructure these thoughts. For example, a child with SAD may feel anxious about separating from
his/her mother because of the thought that the parent will be in a car accident and die when driving
alone (catastrophic thinking). The therapist helps the child challenge thoughts based on accuracy or
value and encourages adaptive, helpful self-talk in response, thereby reducing the effects of the cogni-
tive distortions on current anxiety. These strategies include reflection, decatastrophizing, examining
evidence, and reframing [21, 22]. An example of “examining evidence” is when the therapist asks the
child matter-of-factly to calculate the number of times his/her mother has driven in a car in her life,
along with the number of accidents sustained to demonstrate the low likelihood that an accident will
occur. As an example of decatastrophizing, the therapist might encourage the child to consider what
would happen if a car accident occurred (e.g., “Do you know for sure that your mom would get hurt?”
“Do you think anyone would get help?”). The therapist never promises that the feared outcome will
not happen, but encourages the child to consider a more realistic probability of such an event.
Discussing such abstract topics with children can be difficult. However, introducing the concept
of “thought bubbles” with ideas that pop up in an individual’s head can facilitate the discussion.
When experiencing an unwanted emotion in a particular situation, the place for “helpful” or coping
thoughts can be illustrated. Children practice identifying thought bubbles in cartoons and other peo-
ple, progressively working to identify their own thought bubbles and the specific thoughts that sur-
round their anxious arousal, as well as more helpful “coping” thoughts that they can implement when
feeling anxious.
Problem Solving
The development and application of adaptive problem-solving skills is another feature of CBT for
anxious youth that addresses the behavioral aspect of the tripartite model. Instead of perceiving anxi-
ety as an insurmountable obstacle, children are taught to view it as a problem that can be solved. First,
children identify “the problem” to be solved. Initially, this can be difficult if they feel overwhelmed
by distress or have little experience moving past the unwanted arousal. By identifying the problem, it
becomes concrete and potentially manageable, increasing the opportunity for the child to experience
successful coping. The next step involves “brainstorming” many solutions, including outrageous or
implausible ideas, which helps to facilitate creativity and flexibility. Considering all possibilities
encourages the child to move past the search for the perfect solution. Each solution and its potential
consequences are considered before it is put into action. The consequences of each attempt are dis-
cussed, and all efforts to cope are applauded. The therapist encourages the child to be ready to try an
alternate solution in case the first does not achieve the desired result. The therapist might start with
examples of problems to solve that are not anxiety inducing (i.e., looking for a lost sock) in order to
allow the child to learn the principles of problem solving without becoming overwhelmed by or wary
of the task [23]. Problem solving during anxious situations is later used during exposure tasks.
Exposure Tasks
Facilitating the practice of newly learned coping strategies in the face of real anxiety is considered a
critical catalyst for change as part of the behavioral aspect of CBT [24–28]. Typically, children engage
in “behavioral challenges,” also called exposure tasks, in a graded, hierarchical order that erodes their
patterns of avoidance. The therapist works with the child to collaboratively build a graded hierarchy
based on the child’s and parent’s ratings of anxiety-provoking situations; the therapist does not decide
exposure tasks unilaterally. Exposure hierarchies may list behavioral “challenges” from many anxiety
problem areas, or it may include items specific to only one anxiety disorder (e.g., social phobia: say-
ing “hi” to a stranger, ordering food at a restaurant, initiating conversation with a new peer), depend-
ing on the child’s presenting problem and existing comorbidities. The therapist then works with the
child and parents to determine the specific details for the upcoming challenges. During exposure
tasks, anxious children practice engaging in adaptive coping, learning to distinguish real from per-
ceived threat, and experiencing an increase in their sense of self-efficacy in the face of threat. Different
guidelines for exposure tasks detail specific methods for gauging the design and length of exposures
[26–28]. However, with any exposure task, the therapist considers the severity of the disorder and the
progress that the child has shown in deciding what task is appropriate so that the child is well pre-
pared [23, 29, 30]. Exposures can either be imaginal or in vivo. Imaginal exposures include conjuring
up the image or idea of the feared environment or stimulus, perhaps through role-playing the feared
stimulus, or writing or listening to a narrative of the anxiety-inducing environment. Imaginal expo-
sures are useful for worry about abstract events (e.g., death for GAD) or can be considered lower-
tiered exposures on a fear hierarchy [27]. Imaginal exposures are the primary exposure source in
PTSD treatment, given the ethical concerns in reexposing the youth to a traumatic situation. In vivo
exposures require the child to confront the feared situation in person, which can occur in or out of the
therapy office.
Throughout the exposure, the child’s level of distress is measured on a scale of subjective units of
distress (SUDS) [31], with 0 representing a state of total relaxation and a rating of 8, 10, or 100
(depending on the rating scale used) representing maximum anxiety, arousal, and distress. The thera-
pist collaborates with the child to anchor each rating in definitions that are salient for the child.
Generally, children are encouraged to endure the exposure task until their SUDS rating has decreased
sufficiently and the feared stimulus no longer elicits a strong reaction from the child, but this exact
standard differs somewhat based on the exposure procedure used [27, 28]. During the exposure, the
therapist helps the child to tolerate the distress, reinforcing the benefits of facing one’s fears rather
than avoiding them [27]. Observing a child experience distress may be difficult for a novice therapist,
but research indicates that these exposure tasks do not negatively affect the therapeutic alliance [32].
Following the completion of the exposure task, the therapist (or parent, in the case of exposure tasks
done out of session) praises the child’s efforts to cope with anxiety rather than focusing on the out-
come of the exposure. Post-event processing of the exposure with the child allows him/her to discuss
his/her feelings, thoughts, and appraisals of how well he/she managed his/her anxiety, as well as any
obstacles to coping throughout the process.
To promote self-efficacy, exposures are often repeated to allow the child to build a history of adap-
tive coping such that s/he is able to more quickly and efficiently generate positive coping thoughts and
reduce anxiety in challenging situations. Exposure tasks may be practiced in multiple settings to
encourage generalization [26], which is especially important when the feared stimulus cannot be
accessed in session (e.g., fear of flying [27]). CBT for each anxiety disorder differs in the exact
approach of exposure depending on the theoretical understanding of the disorder and the nature of the
child’s anxiety. For example, exposures for SAD might include graduated challenges in which the
parent or child leaves the therapy session or clinic for varying periods of time. For a child with social
phobia, exposures might involve gradual interactions with others, including making eye contact, play-
ing a game, reading aloud to a group, or ordering for oneself at a restaurant. With public speaking
concerns, treatment might make use of video feedback following speeches, a procedure that has been
associated with decreases in anxiety for subsequent speech exposures [33]. Treatment of OCD uses a
technique called exposure and response prevention (ERP), which focuses on prevention of a ritualized
response while managing obsessive thoughts. More detailed accounts of these procedures will be
addressed later in the chapter, but these examples illustrate the ways in which exposure is adapted to
address the specific nature of the anxiety disorder in question.
Interestingly, research indicates that although exposure tasks are important, the match between
principal anxiety diagnosis (e.g., social phobia) and exposure content (e.g., conducting a survey with
strangers) is not necessarily related to treatment outcome for children with GAD, SAD, or SP [34, 35].
Thus, exposing an anxious child to salient anxiety-provoking situations may be more important than
targeting his/her exact fear. Engagement in graduated exposures helps to build the child’s self-efficacy
in the face of anxiety-inducing situations, which generalizes beyond the situations targeted as part of
the child’s exposure hierarchy. However, these findings may not generalize to the treatment of OCD
and PTSD, given the specific and qualitatively distinct nature of these anxiety disorders.
Relapse Prevention
CBT for pediatric anxiety can vary in length, but termination occurs when children are able to effec-
tively cope with and engage in anxiety-provoking situations in their lives. The child is encouraged to
engage in an “exposure lifestyle” [36] where they routinely approach anxiety rather than follow the
avoidance patterns of their old routines. The need to practice coping, involving all three aspects of the
model (thoughts, emotions, and behavior), can be likened to the need to exercise muscles to increase
and maintain their strength. Parents can help maintain gains by encouraging their child’s bravery and
praising any attempts to approach anxiety using appropriate coping strategies.
Terminating treatment can itself be an anxiety-provoking situation, and the therapist addresses this
concern directly. Before ending treatment, the therapist reviews the goals of treatment and methods to
prevent relapse. In doing so, a distinction is drawn between a “lapse” and a “relapse.” A lapse is a
minor setback that can be expected. In contrast, a relapse suggests more of a return of the larger prob-
lem of anxiety and the dissolution of the coping strategies that were fostered in treatment. But even a
relapse is not a “collapse.” A relapse may suggest that the child is no longer practicing the cognitive
and behavioral strategies introduced in treatment and may require booster sessions to refresh coping
strategies and regain control over anxiety.
While most treatments incorporate these six general CBT components, therapist characteristics, as
well as the delivery format (e.g., individual vs. group) or setting (e.g., school), are important consid-
erations in the treatment for anxious youth.
Therapist Characteristics
An important duty of the therapist early in treatment is to facilitate the development of an alliance and
rapport with the anxious child. Having a trusting relationship is very helpful when the therapist later
asks the child to face his/her fears via exposure tasks. A strong alliance between child and therapist
has been associated with improved treatment outcome in randomized controlled trials of CBT for
pediatric anxiety [37]. In CBT, the therapist’s role is likened to that of a coach [11, 38] who teaches
the child new skills and encourages adaptive coping [29]. In this therapist-as-coach model, emphasis
is placed on the child’s efforts to utilize newly learned skills when anxious, not the elimination of
anxiety. The model of a therapist as a coping coach further normalizes the experience of anxiety and
fosters the alliance with the child [23]. The therapist-coach model introduces the collaborative nature
of treatment by soliciting input from the child at every stage of the intervention.
Some have criticized the use of manualized treatments under the misconception that their applica-
tion is too rigid to address individual problems. It is important to consider that the implementation of
any empirically supported CBTs must be done flexibly to adapt to the particular child, while maintain-
ing fidelity to the original treatment [39]. Therapists are encouraged to be collaborative and creative
in treatment with their clients. For example, the therapist might take into account a particular child’s
difficulty remembering coping thoughts by making a fun coping thought keychain to remind them of
helpful self-talk throughout the day. Thus, manualized CBTs are not rigid recipes to be followed in a
strict manner, but rather detailed descriptions of core elements to be applied in a fun, flexible manner
tailored to the needs of the client.
Delivery Format
Research supports the use of alternate modalities for CBT for pediatric anxiety, including group,
school-based, and family formats [40–44]. Involvement of family members, caregivers, and school
personnel may differ as a function of the child’s presenting difficulties. Even in “individual therapy,”
parents or guardians are often consulted and engaged throughout treatment to help provide structure
and support to the child. In some cases, treatment focuses on transferring control from the therapist to
the parent by educating parents about adaptive responses to anxiety, praising efforts at bravery, and
emphasizing consistent responses when parenting an anxious child [45].
Additionally, research supports the use of school-based prevention and intervention approaches for
anxiety disorders in youth. These programs have been developed to target GAD, SP, and SAD [46] and
PTSD [47]. In-school approaches represent an important delivery venue that may serve to close the
gap between the development of evidence-based treatments and their dissemination in the community,
while increasing the awareness of socioemotional functioning of these children in schools [48–50].
School-based preventative and treatment programs may be delivered in both individual and group
formats [40]. Generally, empirical evaluations of these programs find that children participating in
cognitive–behavioral prevention [51] and treatment [52, 53] programs delivered in the school environ-
ment reliably experience greater reduction in anxiety symptomatology than those in control conditions
[48]. However, successful dissemination of school-based anxiety prevention and treatment relies on
transportability of these treatments [39, 54–56], which represents a continuing challenge in the field.
The structure and format of CBT for pediatric anxiety may vary based on the nature of the child’s
anxiety disorder, the age of the child, and cognitive limitations of the child. Standard administration
of CBT is often recommended for children ages 7 and older [29], although CBT may be used for
younger children with appropriate adaptation. Anxiety CBT for younger children often mirrors that
for older youth but necessitates the use of more developmentally appropriate language and techniques
and places much greater emphasis on the involvement of the child’s parents or guardians [57–59]. By
the traditional CBT approach, parents may be trained, either alone or in groups [60–63], to identify
anxiety in their children, differentially reinforce brave, coping behavior, and to cope with their own
anxiety [58]. Adaptations may be made to address younger children’s difficulty with abstract think-
ing. Research shows that younger children are able to engage in meta-cognitive tasks when they are
made more concrete through the use of labels, pictures, or props (e.g., identifying “red” vs. “green”
thoughts [63]) [59]. Similar adaptations may be made for children with mild cognitive limitations,
although the use of many CBT programs is generally not recommended for children with an IQ below
80. Parent skills training approaches, primarily developed for externalizing disorders (i.e., parent–
child interaction therapy [PCIT]), have been successfully adapted for use with anxiety disorders in
younger youth (i.e., 2–5 years) [64–68]. In these approaches, parents are trained how to address their
children’s anxious thoughts and behaviors while fostering brave or confident behavior [59]. Minor
adaptations may be made for adolescents [69] but generally involve the use of less “childish” lan-
guage and techniques. For example, adolescents may be encouraged to keep a journal rather than use
a treatment workbook.
CBTs for Specific Anxiety Disorders
The following sections discuss the variants of CBT for social phobia, GAD, SAD, OCD, and PTSD.
CBT for each disorder involves many of the same components discussed above, but particular aspects
are emphasized depending on the nature of the anxiety disorder in question. Evidence for efficacy and
effectiveness of each intervention are reviewed, as well as various delivery formats and emerging
novel treatments for each disorder from a cognitive–behavioral framework (e.g., computer-based
treatment, accelerated delivery). A comprehensive discussion of all cognitive–behavioral interventions

for each anxiety disorder is beyond the scope of this chapter. See disorder-specific chapters for a more
detailed discussion of specific treatments.
Social Phobia, Generalized Anxiety Disorder, and Separation Anxiety Disorder
Theoretically, SP, GAD, and SAD are understood as sharing an underlying anxiety construct [70–73].
These disorders frequently co-occur [74], and accordingly, they are often treated with similar inter-
ventions aimed at helping youth to develop coping self-talk and to learn to face their fears [75, 76].
One of the most frequently used and representative examples of CBT for GAD, SAD, and SP has been
Coping Cat [40, 41, 77], a manual-based program developed at the Child and Adolescent Anxiety
Disorders Clinic (CAADC) at Temple University. The Coping Cat program is a 16-week treatment,
divided between teaching anxious youth various skills to manage their fears (first eight sessions) and
then exposing them, in a graded fashion, to these fears (last eight sessions). Unlike some versions of
CBT that move more quickly to exposures and minimize cognitive restructuring or relaxation (e.g.,
ERP for OCD [78]), the Coping Cat program devotes initial sessions to several CBT components
(e.g., general knowledge about anxiety, affect recognition, problem solving, self-talk, and self-encour-
agement and reward for effort). The general CBT principles (e.g., psychoeducation, exposure) are
applied flexibly [69] and can be adapted for the child’s specific presenting problem.
As the most Empirically-Supported Treatment (EST) of anxiety for youth, the efficacy of Coping
Cat has been demonstrated in numerous Randomized Clinical Trials (RCTs) conducted by several,
independent research teams [77]. As such CBT, and Coping Cat specifically, is considered a “proba-
bly efficacious” treatment for childhood SP, GAD, and SAD according to guidelines set by Chambless
and Hollon [79] and the American Psychological Association (APA) Task Force [80]. These RCTs
have shown moderate to large effects when comparing Coping Cat to no treatment, a placebo, or an
alternative treatment for youth with SP, GAD, and SAD [11, 40, 81, 82]. Consistent with a cognitive–
behavioral framework, research supports that favorable treatment outcomes are mediated by reduc-
tions in negative, anxious cognitions [83, 84]. Moreover, Coping Cat-based CBT appears to offer
similar benefits to pharmacological treatments for anxiety [77]. In the Child Anxiety Multimodal
Study (CAMS), a recent, multisite, RCT, 488 youth (ages 7–17 years) with SP, SAD, and GAD were
treated with either 14 sessions of CBT based on Coping Cat, sertraline, or their combination. CBT and
sertraline improved anxiety in 59.7 % and 54.9 % of youth, respectively, with combined treatment
resulting in a significantly superior response rate of 80.7 % [77].
CBT has been associated with favorable long-term outcomes [85]. Children with GAD, SAD, or
SP treated with the Coping Cat CBT program have been found to maintain their gains at 1-year and
longer follow-ups, ranging from 3.5 years [86] to as many as 7.4 years after treatment completion [86,
87]. Further, successful treatment of these disorders has been associated with reduced substance use
problems in late adolescence and early adulthood [5, 6].
Effects of Comorbidity
CBT for SAD, SP, and GAD are equally effective in boys and girls as well as in children of varied
ethnicities, though youth from single-parent homes and ethnic minorities may be more likely to ter-
minate treatment prematurely [88–90]. Given that the majority of youth will have at least one addi-
tional comorbid anxiety or other psychiatric diagnosis [74, 91], it is worth noting that the efficacy of
Coping Cat as well as several other CBT programs has been established in youth with multiple comor-
bidities (e.g., additional anxiety, attention, conduct, or mood disorders) as long as SAD, GAD, or SP
was considered the principal concern [77, 88]. However, for these children, successful gains in anxiety
CBT may not always generalize to emotions other than those targeted in the primary intervention
[92]. The impact of comorbid mood symptoms along with demographic characteristics on treatment
outcome is not clear. Some studies suggest that age, greater internalizing severity, and depressive
symptoms are inversely related to individual CBT improvement [93–95], while others have shown
CBT to be effective in children with varying levels of severity [77] and comorbid anxiety and depres-
sive disorders [77, 88]. Although children with developmental disorders and intellectual impairments
have typically been excluded from controlled research studies, case studies have shown that tailoring
CBT for children with special needs can lead to successful outcomes [91]. Further, some CBT pro-
grams for anxiety disorders in youth, such as the building confidence [96] and “Cool Kids” interven-
tions [97], have been successfully adapted for use in high-functioning children with autism spectrum
disorders [98, 99].
Alternative Delivery Formats
CBT for SP, GAD, and SAD, typically provided in one-to-one therapeutic interaction, can be delivered
in a variety of formats, including group- and family-oriented interventions, weekly or biweekly ses-
sions, or novel, electronic formats, designed to increase the portability of CBT to school, homes, and
community clinics as opposed to specialty research settings [41, 100]. When delivered in a family
format, the 16 sessions of the Coping Cat are adapted to include parents in each session (as opposed
to conducting two parent-only sessions in the individual treatment) [40]. Parents are taught the CBT
principles along with their child and are trained to become a “CBT coach” for their child between ses-
sions. Other family CBTs for SP, GAD, and SAD, akin to Coping Cat-based Family CBT (FCBT [41]),
have “family anxiety-management” sessions [101] or emphasize parent-specific skills (communica-
tion training) [102]. Whereas both individual and group modalities of CBT for GAD, SP, and SAD
may be considered efficacious treatments according to Chambless and Hollon’s criteria [79], further
studies of family CBT, a possibly efficacious treatment, are needed to reach this standard [40]. Family
CBTs have been indicated for subgroups of children, such as youth with anxious parents [103, 104] or
youth with moderate autism spectrum disorder symptoms, whose ability to engage in treatment and
practice CBT skills outside of session may be facilitated by parental involvement [105]. However, the
relevant benefits of individual versus family modalities for anxious youth, overall, are unclear [41,
103]. In one RCT (n = 161) that focused on the relative efficacy of individual versus family treatment,
youth with anxiety disorders were equally likely to benefit from individual (57 % improved) and fam-
ily (55 % improved) modalities of CBT, though the improvement of youth assigned to a family educa-
tion and support condition (i.e., a non-CBT treatment) was significantly less (35 % improved) [41].
As a more efficient and potentially more affordable treatment option, group formats of CBT have
also been developed, often in combination with family CBT programs [106–108], and found to offer
similar benefits to individual CBT. In a 1-year follow-up study of youth treated with individual ver-
sus group versions of the Coping Cat, Flannery-Schroeder and colleagues [100] found no significant
differences in treatment outcome between groups (81 % vs. 77 % of treated youth no longer met
criteria for an anxiety disorder). Similar to studies on family versus individual CBT, the benefits of
family involvement in group CBT for GAD, SAD, and SP appear beneficial in some [108], but not
all studies [107].
There is some empirical support for several novel delivery formats for CBT including stepped care
and electronic or computer-based interventions. A non-RCT of CBT for 133 children (ages 8–12) with
anxiety disorders provided preliminary support for the use of standardized, but also tailored treatment
interventions [109]. Whereas 45 % of the sample improved and discontinued after ten sessions, 37 more
(28%) improved with an additional five or ten sessions (i.e., stepped care). Much recent research has
also focused on the development and evaluation of more cost-effective and transportable electronic
CBT approaches [110]. Interactive, computer-assisted versions of the Coping Cat as well as various
other child CBT programs have been developed and received empirical support [111, 112]. Further, a
recent RCT comparing clinic-based and electronic CBTs found that online delivery of CBT with
minimal therapist support was as efficacious as a clinic-based CBT in reducing child anxiety, support-
ing the viability and potential promise of this novel approach for the future delivery and the dissemi-
nation of CBT for pediatric anxiety [113].
Effectiveness
Studies of the effectiveness of CBT (i.e., CBT’s performance across more diverse communities and
settings as opposed to controlled research samples) are emerging. In an RCT comparing CBT to usual
care in a community clinic, CBT significantly reduced anxiety in 66.7 % of youth, an outcome that
was comparable to usual care, which demonstrated improvements in 73.7 % of youth [114]. The
authors suggest that the effects of CBT were not optimal because the therapists did not uniformly
implement exposure tasks, which are often considered the most important catalysts for change in
CBT. Additionally, youth receiving care-as-usual were also receiving multiple additional services, so
it is unclear if decreases in anxiety could be attributable to the therapy they received. A study con-
ducted in a community clinic setting in China found that youth treated with CBT showed significant
reductions in anxiety compared to those on the wait list at posttreatment, 3-month and 6-month fol-
low-ups, supporting the applicability of this treatment in non-Western cultural settings [83]. Together,
these findings suggest the need for further, larger studies of the effectiveness of CBT for SAD, GAD,
and SP to support the dissemination of these treatments on a large scale [114], with a special emphasis
on the fidelity of the treatments when implemented in community clinics.
Obsessive–Compulsive Disorder
According to the Practice Parameters for the Assessment and Treatment of Children and Adolescents
with OCD [115], CBT with exposure and response prevention (ERP) has demonstrated significant
effects in reducing symptoms for youth with OCD, both alone or when combined with pharmacotherapy
[116, 117], and is recommended as a first-line treatment for youth with OCD [116, 118, 119]. CBT for
OCD targets characteristic obsessions and compulsions through exposure and cognitive restructuring
methods similar to those used for other anxiety disorders in youth. However, CBT for OCD specifically
emphasizes exposure tasks and response prevention [78]. ERP therapy for OCD involves gradually
exposing patients to anxiety-provoking stimuli while they refrain from performing rituals or engaging
in avoidance behavior. Similar to other anxiety disorders, cognitive restructuring strategies guide the
youth to reduce anxiety during the exposure. For example, youth may be guided to refute obsessive
thoughts underlying compulsions (e.g., “my hands are covered in germs”), which may serve to reduce
anxiety when they are prevented from engaging in compulsions (e.g., washing hands). Thus, the use of
cognitive coping strategies may facilitate the process of ERP and enhance compliance [120].
Among the CBT approaches for youth with OCD [121], the March and Mulle manual [120] is an
empirically supported example of an ERP protocol. This treatment contains 14 weekly sessions across
12 weeks and includes the following components: (1) clinical evaluation and assessment, (2) psycho-
education, (3) cognitive restructuring, (4) severity ratings of symptoms and establishment of a fear
hierarchy, (5) gradual ERP based on the symptom hierarchy, (6) homework, (7) parent sessions, and
(8) relapse prevention. In addition to the March and Mulle individual protocol [120], CBT/ERP for
youth with OCD has been delivered in various formats (e.g., individual, group, family-focused) and
with different session frequencies (e.g., weekly, daily) [122–126].
Evidence from clinical trials supports the efficacy of CBT/ERP for youth with OCD [117, 119,
123, 127]. A recent meta-analysis [128] reviewed four RCTs comparing CBT to control conditions
and found a significant effect size supporting the efficacy of CBT/ERP for youth with OCD.
Additionally, the efficacy of CBT/ERP for pediatric OCD was recently tested in a large multisite ran-
domized controlled trial (The Pediatric OCD Treatment Study [POTS I]) [129]. Youth with OCD
(N = 112; aged 7–17) were randomized into four groups: individual CBT, medication (sertraline), CBT
and medication combined, and pill placebo. Eighty-seven percent of the youth completed the 12-week
treatment, and intent-to-treat analyses revealed that all treatment conditions yielded significantly
superior outcomes at posttreatment as compared to the placebo condition. Specifically, combined
treatment was superior to either CBT or medication alone, with no significant differences found
between CBT- and medication-alone conditions. When measuring treatment outcome in terms of the
remission rate (evidenced by score of Children’s Yale–Brown Obsessive–Compulsive Scale
[CY-BOCS] < or = 10 at posttreatment) [130], the combined (54 % remission rate) and CBT (39 %)
conditions significantly outperformed medication (21 %) and did not significantly differ from one
another [129]. This result confirms CBT as a first-line treatment for youth with OCD. Secondary
analyses suggested comorbidity, poor insight, greater symptom severity or functional impairment,
and higher family accommodation as impediments to optimal success from CBT for youth with OCD
[131]. These predictors are consistent with findings from other studies [132, 133].
Empirical evidence supports the use of ERP protocols across various delivery formats. Barrett and
colleagues [122] added a family component [42] to March and Mulle’s [120] treatment and compared
individual and group CBT with this addition to a wait list control. Whereas both individual and group
treatments obtained superior outcomes compared to controls, there were no significant differences
between individual and group CBT at posttreatment and follow-up [122, 123]. Manualized intensive
treatment (5 sessions per week) has also demonstrated efficacy in treating youth with OCD [42, 118,
125]. Remarkably, there was no difference between weekly and intensive schedules in terms of treat-
ment outcome [134], which implies that intensive treatment schedules allow the possibility of
significant gain in a much shorter period of time than in weekly treatment, provided the family is able
to comply to a more demanding treatment schedule. Treatment for pediatric OCD has also been tested
in a technology-based modality. Findings from a pilot study examining a telephone-based CBT for
youth supported the effectiveness, acceptability, and feasibility of such delivery format for pediatric
OCD [135]. Overall, diversified delivery formats can be used to successfully treat pediatric OCD
while fitting the particular needs of the family or youth [42, 119].
Effectiveness
Recent work has focused on evaluating the effectiveness of current pediatric OCD treatments in com-
munity settings. Specifically, two studies [125, 126] implemented manualized CBT-ERP treatment in
community outpatient clinics achieving response rates over 60 %. Research also supports the effec-
tiveness of group-based CBT-ERP in the community setting [128]. Additionally, to develop and test a
more easily disseminated protocol, the Pediatric OCD Study team has been conducting a second study
(POTS II) [136] to compare two treatment protocols: a “single doctor” model (with both CBT and
medication management delivered by a child psychiatrist) and a “dual doctor” model (with CBT
delivered by a psychologist and medication management a child psychiatrist). Although the study
contains elements of an efficacy study, the primary aim is to investigate the effectiveness of both
models. The results of this study will be revealed in the near future.
Post-traumatic Stress Disorder
CBT for PTSD typically involves exposure tasks, cognitive restructuring, and anxiety-management
skills. In these treatments, exposure tasks, either imaginal or in vivo, consist of confrontation with
fearful memories of the trauma [137, 138]. Exposures are said to be effective by (1) reducing condi-
tioned fear responses associated with trauma cues and (2) challenging cognitive distortions surround-
ing perceived danger and threat [139]. Exposure-based CBT has been found to be effective for youth
with PTSD [140–143]. However, Nixon et al. [144] determined that CBT (with exposure) did not
significantly outperform cognitive therapy (CT) among 33 children with PTSD following a single-
incident trauma (65 % CBT vs. 56 % of CT no longer met criteria for PTSD posttreatment). The
authors acknowledged that CT, while lacking in formal exposure tasks, may include some element of
exposure (e.g., discussion of the negative effects of avoidance and necessary retelling of the trauma).
Treatment may require consultation with schools and others involved in the child’s life and should
take into account psychosocial stressors, risk factors, severity of PTSD symptoms, current cognitive
and developmental functioning, family and parenting factors, and comorbidities [145]. In their review,
Cohen and Mannarino [146] cited established treatments for PTSD, including trauma-focused cogni-
tive–behavioral therapy (TF-CBT) [147], cognitive–behavioral therapy for PTSD (CBT-PTSD) [148],
and CBT for trauma in schools (CBITS) [44].
TF-CBT consists of 12–15 sessions, which include both the child and the parents [149]. Intended
for children ages 3–18 with a history of diverse traumas, TF-CBT’s components include a psychoedu-
cation/parenting component, relaxation, affect modulation, cognitive processing, trauma narrative,
in vivo exposure and mastery of trauma reminders, conjoint child–parent sessions, and enhancing
safety and future development [150, 151]. The efficacy of TF-CBT has been supported in RCTs for
school-age children [152, 153] and, more recently, for very young children (ages 3–6) [154]. For
example, in a study of 229 youth (aged 8–14) who had been sexually abused, TF-CBT was superior
to child-focused therapy on most measures, although 21 % of children treated with TF-CBT still met
diagnostic criteria for PTSD posttreatment [152]. TF-CBT has been adapted for underserved popula-
tions, including Hispanic and African American youth and their families [155], children impacted by
the terrorist attacks [156], children with traumatic grief [157, 158], and children exposed to intimate
partner violence [159].
An alternative model was developed by Smith and colleagues [148], who created an individual
treatment (CBT-PTSD) for children who meet criteria for PTSD following single-event traumas.
Treatment is based on the Ehlers and Clark [160] model, which postulates that PTSD is maintained
through faulty memories of the trauma, cognitive misappraisals, and dysfunctional coping strategies.
As this model has been applied to children [161], it also takes into account parental reactions [162].
CBT-PTSD, a manual-based treatment, consists of ten individual sessions and parent–child sessions
as needed. Treatment components comprise psychoeducation, activity scheduling, writing and draw-
ing trauma narratives, cognitive restructuring, visiting the trauma site, stimulus discrimination, target-
ing nightmares, and behavioral experiments. In an initial RCT consisting of 24 children with PTSD,
those receiving CBT-PTSD showed significantly greater improvement in PTSD symptoms, depres-
sion, and anxiety compared to wait list [148]. Additionally, 92 % of CBT-PTSD participants no longer
met criteria for PTSD at posttreatment, and gains were maintained at 6-month follow-up. Changes in
maladaptive cognitions mediated improvements as a result of CBT treatment [20], which provides
support for the cognitive model of PTSD [148].
A school-based group approach, the CBITS program [44], is a ten-session CBT for implementation in
schools to address symptoms of PTSD, anxiety, and depression resulting from exposure to violence.
Treatment covers relaxation, cognitive restructuring, exposure to stress or trauma memory, and social
problem solving. An initial RCT compared 61 sixth-grade students assigned to CBITS and 65 assigned
to wait list. Three months post-intervention, students in the CBITS group showed significantly greater
decreases in PTSD symptoms, depression, and psychosocial impairment compared to the wait list
controls [163]. Further, an adaptation of CBITS, the Mental Health for Immigrants Program (MHIP),
has initial support among Latino immigrant youth exposed to community violence [164].
Effectiveness
Growing support exists regarding the efficacy of CBT interventions for children with PTSD [145].
Nonetheless, future research regarding the dissemination and implementation of evidence-based
treatments for youth with PTSD into the community, particularly among ethnic minority groups, is
necessary [155]. Several studies have been conducted; others are ongoing [165]. The Child and
Adolescent Trauma Treatments and Services (CATS) Consortium [47] conducted a large-scale imple-
mentation study of trauma treatments for youth affected by the World Trade Center terrorist attack in
New York City. The investigators compared TF-CBT for children and trauma and grief component
therapy for adolescents (includes common components with TF-CBT [166]) with moderate to severe
trauma symptoms. Youth with mild trauma symptoms received a brief CBT skills intervention [167].
At a 6-month follow-up assessment, the moderate–severe group experienced an improvement in clini-
cal symptoms to the mild range, while the mild group also reported lower scores. The authors noted
that both therapies were feasibly implemented in a variety of settings, including outpatient, commu-
nity, and school-based clinics [47]. In another field trial, New Orleans children with PTSD post-
Hurricane Katrina were randomized to receive either CBITS in school or TF-CBT in community
clinics. Although both led to significant improvements in PTSD symptoms, school-based treatment
was found to be much more accessible to families [168].
Summary
Overall, CBT has been found to be an efficacious treatment for anxiety disorders in children and ado-
lescents and is often recommended as the first line of treatment [9]. Despite the well-documented
evidence regarding CBT’s success in treating anxiety disorders in youth, future work is required to
investigate the specificities of anxiety CBTs for different populations of youth, including greater con-
sideration of developmental levels and cultural groups, continued exploration of novel augmentations
for nonresponders, as well as further investigation of dissemination and implementation in the
community.
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Psychopharmacology of Pediatric Anxiety Disorders
Justin W. Mohatt, Alex Eve Keller, and John T. Walkup
Abstract There are a number of pharmacological approaches used in treating pediatric anxiety dis-
orders. Selective serotonin reuptake inhibitors (SSRIs) are first line treatment, but there are many
other treatment options for nonresponders including serotonin norepinephrine reuptake inhibitors
(SNRIs), tricyclic antidepressants (TCAs), benzodiazepines (BZDs), buspirone, and other investiga-
tional and augmenting agents. This chapter will examine the evidence base for the pharmacological
treatment of pediatric obsessive–compulsive disorder (OCD), non-OCD anxiety disorders, and post-
traumatic stress disorder (PTSD). Additionally, augmentation strategies and general clinical consider-
ations are presented to aid in formulating an approach to both simple and complex patients.
Keywords Pediatric • OCD • Anxiety disorders • SSRI • Psychopharmacology • Evidence base
Introduction
There is a substantial and growing literature supporting the use of selective serotonin reuptake inhibi-
tor (SSRI) antidepressants for treatment of pediatric anxiety disorders. A number of SSRIs have
received United States Food and Drug Administration (FDA) approval for use in children and ado-
lescents for obsessive–compulsive disorder (OCD) and major depressive disorder (MDD) (see
Table 1). Although no SSRI is FDA approved for use in anxiety disorders other than OCD, there is
very good evidence supporting their use in separation anxiety disorder (SAD), generalized anxiety
disorder (GAD), and social phobia (SoP) [1]. Even though SSRIs are the treatment of choice, a num-
ber of other medications can be used to treat pediatric anxiety disorders, including serotonin norepi-
nephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), benzodiazepines (BZDs),
and other agents (i.e., buspirone). Despite demonstrated efficacy of antidepressant medications for
childhood anxiety disorders, a substantial portion of children and adolescents do not respond. There
is a small literature describing next steps for the pharmacological treatment of partial and nonre-
sponders to SSRIs.
Use of a medication to treat a disorder for which there is no FDA approval is considered “off label”
use. It is important to note that while FDA approval implies evidence of safety and efficacy, the lack
J.W. Mohatt (*) • J.T. Walkup

Child Division, Department of Psychiatry, Weill Cornell Medical College, New York, NY, USA
e-mail: jum9071@med.cornell.edu
A.E. Keller
Department of Child and Adolescent Psychiatry, Weill Cornell Medical College, New York, NY, USA
290 J.W. Mohatt et al.
Table 1 Selective serotonin reuptake inhibitor (SSRIs)

Primary metabo- Half life
Pediatric lism and active CYP450 system parent/active
Medication indications Starting dose Max dose metabolism (AM) effects metabolites
Fluoxetine OCD (7–17 10 mg/day 60 mg/day 2C19, 2D6 2D6 inhibitor Parent: 4–6
years) days
MDD (8–18 AM: norfluoxetine 3A4 inhibitor AM: 4–16
years) days
Sertraline OCD (6–17 25 mg/day 200 mg/day 2C9, 2D6, 3A4 3A4 inhibitor 26 h
years) (6–12 years)
50 mg/day 2D6 weak
(13–17 inhibitor
years)
Paroxetine None 10 mg/day 60 mg/day 2D6 3A4 inhibitor 21 h
Fluvoxamine OCD (18 years) 25 mg/day at 200 mg/day 1A2, 2D6 3A4 inhibitor 15.6 h
night div
1A2 inhibitor
Citalopram None 10 mg/day 60 mg/day 2C19, 3A4 2D6 weak 35 h
inhibitor
Escitalopram MDD (12–17 10 mg/day 20 mg/day 2C19, 2D6, 3A4 2D6 weak 27–32 h
years) inhibitor
of FDA approval does not mean that a medication does not have substantial evidence of efficacy or
safety. Prescribers who practice “evidence-based medicine” for children with anxiety disorders will
inevitably prescribe “off label” as the FDA labeling process does not reflect the complete evidence
base. Even if there is good evidence of medication efficacy in the scientific literature, if neither the
manufacturer nor the FDA pursues labeling, the medication will not receive an indication. Therefore,
practicing “evidence-based medicine” in pediatric psychiatry often means following the scientific
literature rather than only using FDA-approved medications.
In this chapter, we will review the evidence base for the use of medications in OCD, non-OCD
anxiety disorders, and post-traumatic stress disorder (PTSD) in children and adolescents and will
discuss the small literature of pharmacological augmentation strategies. This structure, which sepa-
rates OCD and PTSD from other anxiety disorders as well as each other, is consistent with the orga-
nization of current large studies and with the most recent changes in nosology.
Pharmacologic Agents
As an introduction to the psychopharmacology of pediatric anxiety disorders, this chapter first pro-
vides a brief overview of neurotransmitters and fundamentals of pharmacokinetics focusing primarily
on drug metabolism. This is followed by a review of the major medication categories including SSRIs,
SNRIs, TCAs, BZDs, mirtazapine, and buspirone. Primary indications, pharmacological effects, and
adverse effects are discussed for each medication or category of medications. Information on starting
doses and dose ranges are included in the accompanying tables along with reiteration of important
metabolic effects.
Neurotransmitters
Neurotransmitters are the chemicals that nerve cells use to communicate with one another. They are
stored in bundles in nerve cells and are released into the space between nerve cells (the synapse) when
Psychopharmacology of Pediatric Anxiety Disorders 291
stimulated to do so. The nerve cell from which they are released is referred to as the presynaptic
neuron. When the neurotransmitter is released into the synapse, it interacts with receptors on the sec-
ond nerve cell (postsynaptic neuron). Neurotransmitters are then removed from the synapse in one of
two ways. They are either degraded within the synapse or removed from the synapse by reuptake
pumps in the presynaptic neuron.
The major neurotransmitters discussed in psychiatry are serotonin, dopamine, norepinephrine, ace-
tylcholine, gamma-aminobutyric acid (GABA), and glutamate. Psychotropic medications modulate
the activity of these neurotransmitters in a variety of ways. Some agents work by mimicking the
effects of a neurotransmitter. These are called agonists. BZDs act as agonists by mimicking the effects
of GABA at its receptors. Other agents work by inhibiting the effects of neurotransmitters. These are
called antagonists. Older antipsychotic medications act as dopamine antagonists by blocking its effect
at dopamine receptors. Many of the medications used to treat anxiety act by blocking the reuptake of
neurotransmitters from the synapse. For example, SSRIs selectively block the reuptake of serotonin
from the synapse.
Pharmacokinetics
Pharmacokinetics is the underlying factors that determine how a given dose of medication leads to a
particular concentration of the drug in the body. The four processes that determine a drugs concentra-
tion are absorption, distribution, metabolism, and excretion. In general terms, absorption and distribu-
tion determine the rate at which medication effects are felt by patients. Metabolism and excretion
affect the rate at which these effects stop.
A basic understanding of drug metabolism is critical for understanding the appropriate use and
dosing of medications in anxiety disorders. After medications are absorbed in the gastrointestinal
tract, they undergo metabolism in the liver, referred to as “first-pass” metabolism, before entering the
larger circulation on the body. The proportion of medication that remains in “parent” form after first-
pass metabolism is called the bioavailability. While the “parent” drug is usually the effective com-
pound, some medications also have active metabolites (i.e., fluoxetine and clomipramine). As a patient
continues to take doses of a medication, the blood levels of the medication steadily rise until they
reach a point at which the rate of absorption equals the rate of removal, which is referred to as a
“steady-state” level. The rate at which a medication reaches steady-state is affected by how quickly a
medication is metabolized or eliminated. For medications with rapid metabolism and excretion,
steady-state is reached more quickly than for medications that are slowly metabolized or excreted by
the body. The time it takes to reduce the blood concentration of a single dose of medication by half is
called the “half-life.” Half-life can be used to predict the time to steady-state, usually approximately
five half-lives. This can be useful in determining the frequency of medication dosing. Medications
with shorter half-lives may need to be dosed more frequently than ones with longer half-lives. Some
medications require monitoring of therapeutic levels and knowledge of when steady-state will be
reached helps guide when to check the level to get accurate results.
Metabolism of most psychotropic medications within the liver is performed by an extensive sys-
tem of enzymes called the P450 system. A full explanation of the P450 system is beyond the scope of
this chapter, and readers interested in learning more are referred to primary psychopharmacology
textbooks. For the purposes of this chapter, it is important to be familiar with the primary P450
enzymes involved in the metabolism of medications used to treat anxiety and to understand the mech-
anisms by which medications can alter the P450 metabolism of other medications and sometimes
themselves.
The most common P450 enzymes involved in metabolism of psychotropic medications are 2D6,
2C19, 3A4, and 1A2. If a medication is metabolized by a given P450 enzyme, it is referred to as a
“substrate” of that enzyme. In addition to being metabolized by the enzymes, medications can affect
the rate at which the enzymes metabolize drugs. Medications that slow the metabolism by an enzyme
are called inhibitors, and medications that increase the rate of metabolism by an enzyme are called
inducers. If a medication inhibits a P450 enzyme, this can lead to elevations in blood concentrations
of any medication that is a substrate of the enzyme. For example, fluoxetine is both a substrate of 2D6
and an inhibitor of 2D6 metabolism. If a medication such as risperidone, which is also a 2D6 substrate
is added to the fluoxetine, levels of risperidone will be higher than otherwise expected for a given
dose. In addition, because fluoxetine is itself a 2D6 substrate, increases in its dose can lead to much
higher levels of the drug than expected if it was not inhibiting its own metabolism. Most psychotropic
medications have linear pharmacokinetics, meaning that doubling of the dose of medication will lead
to a doubling of concentration of medication in the body. However, some medications like fluoxetine
that inhibit or induce their own metabolism have what is called nonlinear pharmacokinetics.
Children and adolescents have more efficient livers and kidneys than adults. This means that they
have more efficient metabolism and elimination than adults as a general rule. Children can often toler-
ate adult doses of medication because of their faster metabolism and elimination. At the same time,
children are not just small adults and they are often more sensitive to side effects than adults. Because
each medication is different in its effects, side effects, and pharmacokinetics, it is impossible to make
general statements about dosing of medications. It is important that prescribers are familiar with each
agent and review the specific information for each when prescribing for children and adolescents.
Familiarity with the dosing protocols in clinical trials can provide a rough guideline for dosing and
titration in order to avoid under-dosing or excessively prolonged or rapid titration.
Selective Serotonin Reuptake Inhibitors
The SSRIs are first line agents for childhood anxiety disorders due to consistent and substantial evi-
dence of safety and efficacy in a number of high quality clinical trials. The SSRIs available in the
United States include regular and sometimes extended release preparations of the following: fluoxetine
(Prozac, Prozac Weekly), paroxetine (Paxil, Paxil CR), fluvoxamine (Luvox, Luvox CR), regular
release sertraline (Zoloft), citalopram (Celexa), and escitalopram (Lexapro). At this time, there is
FDA approval for fluoxetine for OCD (age >7) and MDD (age >12), sertraline for OCD (age >6),
fluvoxamine for OCD (age >8), and escitalopram for MDD (age >12). There are no medications with
FDA approval for non-OCD anxiety disorders. However, there is considerable evidence supporting
their use in the non-OCD anxiety disorders. Table 1 provides a summary of the SSRIs including infor-
mation on starting doses, maximum doses, and metabolism.
Pharmacological Effects
The primary mechanism of action of the SSRIs is the selective inhibition of serotonin reuptake from
the synaptic cleft with very little or no effect on dopamine or norepinephrine uptake. The SSRIs differ
however in their activity for other receptors, pharmacokinetics, metabolic pathways, and risk for
drug–drug interaction. Hence, some patients may respond to or tolerate one SSRI better than another.
Long half-life SSRIs are preferable for those who miss an occasional dose as they have minimal with-
drawal effects. However, the longer half-life of the drug may result in a greater duration of side effects
for patients after discontinuation. For example, fluoxetine has a long half-life. If a patient develops
adverse effects on fluoxetine and it is discontinued, the adverse effects will persist longer than they
would for a medication like paroxetine with a shorter half-life. On the other hand, shorter half-life
SSRIs like paroxetine may not be the best choice for less adherent patients; these medications have a
greater risk for withdrawal effects but also clear quickly with discontinuation. Additionally, most
SSRIs have linear accumulation (linear pharmacokinetics), whereas others (fluoxetine and parox-
etine) have nonlinear and less predictable accumulation. The desired clinical effects of SSRIs are
due to alteration of receptor sensitivities, not the immediate increase in serotonin levels seen with
SSRI administration. As a result clinical effects are only observed after several weeks on the
medication.
Some SSRIs have more prominent drug–drug interactions (e.g. fluoxetine, paroxetine, fluvoxamine).
SSRIs with minimal drug–drug interactions (e.g., sertraline, citalopram, and escitalopram) may be
better first choices if the doctor anticipates combined pharmacotherapy. The knowledge of how the
SSRIs differ will likely inform drug choice as much or more than results of efficacy studies and help
improve outcome and minimize side effects.
Adverse Effects
The SSRIs have relatively benign safety and side effect profiles, especially when compared to their
predecessors, the TCAs and monoamine oxidase inhibitors (MAOIs). Compared to the TCAs, the
SSRIs are less sedating and cause less weight gain because of low anti-histamine effects. SSRIs have
less anti-cholinergic effects, causing less dry mouth, constipation, and urinary retention than TCAs
and MAOIs, and they have very few adrenergic effects and therefore have low risk of orthostatic
hypotension. The SSRIs have no effect on Na+ channels. As a result, they do not carry the same seri-
ous cardiac risks in overdose as the TCAs. Finally, they do not burden the patient with the dietary
restrictions as the MAOIs.
Side effects generally occur early in the course of treatment and are likely due to the rapid and
dramatic increases in serotonin concentration in the brain and periphery. Headache, nausea, diarrhea,
constipation, and loss of appetite are common early side effects but usually mild, transient, and very
responsive to adjustments in the dosage. Few side effects present late in the course of treatment.
Among the most common and problematic adverse events in clinical trials is central nervous sys-
tem activation, a phenomenon called behavioral activation, which can vary in severity from mild
internal restlessness to insomnia, significant impulsivity, and hyperactivity. Activation occurs early in
treatment and with dose adjustments. Preadolescent patients appear more likely to experience behav-
ioral activation than adolescents [2]. Rates of activation by SSRIs have ranged from approximately
11 % to as high as 50 % [2–5]. Activation is often easily managed by lowering the dose of medication,
though significant reductions may result in loss of the desired clinical effect. In children who cannot
tolerate the activation side effects of SSRIs, a trial of the non-activating antidepressants (e.g., clomip-
ramine, duloxetine, mirtazapine, imipramine, or nortriptyline) may be useful.
Like other antidepressants, the SSRIs also have been associated with mania. Data from large ran-
domized controlled trials (RCTs) indicate that the rates are very low (<2 %) especially compared to
behavioral activation, which does not present with the euphoria, grandiosity, and mood changes of
mania. Mania can occur at any point in treatment whereas behavioral activation presents early in treat-
ment or with dose titration [6–9]. Of note, rates of antidepressant induced mania are substantially
higher in retrospective case studies (5.4–55 %) likely reflecting less stringent screening for risk fac-
tors (e.g., familial history of bipolar disorder) in general clinical populations than RCTs [6]. While a
family history of mania, especially a parent with bipolar disorder, is not a contraindication to SSRI
use, clinicians must proceed with caution and be watchful for any emergent symptoms of a mania in
this population.
Sexual dysfunction is another side effect of SSRIs. This includes reduction in or loss of libido for
both males and females. Additionally, for male patients, it can include an inability to get or maintain
an erection, delayed ejaculation, or inability to ejaculate. In female patients, it can lead to delayed
orgasm or anorgasmia [10]. Adolescents should be monitored for sexual side effects, which they may
not discuss spontaneously and which may lead to reduced medication adherence. It is important to lay
the base for these discussions by including education about sexual side effects in the informed consent
process with adolescents. Going forward, direct questioning about sexual side effects in a nonthreat-
ening manner using clear medical terminology will be most effective.
Sexual effects can be dose dependent. Therefore, reducing the dose is one option for managing
them. Other options include switching to an antidepressant with less sexual side effects (i.e., mirtzap-
ine, nefazodone), adding an agent to promote libido (i.e., buproprion), or adding an agent to improve
erectile function (i.e. sildenafil or tadalafil) [11, 12]. Choice of agent should be guided by the underly-
ing psychiatric disorder being treated and the underlying pathology of the dysfunction (loss of libido
vs. erectile dysfunction vs. anorgasmia vs. overall dysfunction).
A syndrome of apathy, manifested by lack of motivation in the absence of sedation or depression,
can occur with the SSRIs. This is dose dependent, may not appear until later in titration, and does not
tend to improve with time. Reducing the dose may help. If dose reduction is ineffective, then switch-
ing to a different class of antidepressant may be necessary.
Abrupt discontinuation after long-term use of SSRIs has been associated with discontinuation
effects including unusual sensory experiences and a flu-like syndrome. As noted previously, discon-
tinuation effects appear to be more common in SSRIs with a short half-life as compared to those with
a longer half-life. Slow and graduation discontinuation is generally recommended for the SSRIs both
to avoid withdrawal effects and to reduce the chance of rapid return of anxiety or depressive symp-
toms. The speed of reduction can be guided in part by pharmacokinetics. Medications like paroxetine
with short half-lives require a slower dose reduction to avoid or reduce discontinuation effects, while
medication like fluoxetine can often be discontinued quickly without notable discontinuation effects.
It is impossible to make general statements about how quickly to lower a given medication because
individuals are widely variable in their sensitivity and tolerance of these effects.
Serotonin syndrome is a potentially fatal complication of treatment with any medication that
increases serotonin levels including the SSRIs. It is usually due to the combined effects of two or
more drugs that both elevate serotonin levels. Symptoms of serotonin syndrome include agitation,
hyperreflexia, myoclonus, tremor, ataxia, agitation, diarrhea, nausea, vomiting, fever, heavy sweating,
shivering, and mental status changes such as confusion and hallucinations. Serotonin syndrome is a
medical emergency and should be treated as such. Once it is recognized, the offending medications
must be stopped and the patient should be admitted to the hospital for monitoring and supportive care.
Appropriate care can include medications to reduce agitation, muscle stiffness and myoclonus, cypro-
heptadine to block serotonin production, and IV fluids for hydration. If appropriately recognized and
treated, patients usually recover quickly and well.
All antidepressants, including the SSRIs, carry an FDA Black Box warning label indicating that
they may increase the risk of suicide in patients 24 years and younger. The FDA added labeling about
increased suicide risk in October 2004 following an analysis of pooled data from prior antidepressant
trials that found 4 % of subjects on antidepressants reported increased suicidal thoughts or behaviors
compared to 2 % of patients on placebo. There were no actual suicides among the approximately
4,400 children and adolescents in these studies. Subjects in the studies carried diagnoses of MDD,
OCD, and other anxiety disorders. In 2007, the label was expanded to include adults 24 years or
younger. For further details about the FDA review, please refer to the FDA website (www.fda.gov).
Information about the black box warning written specifically for parents can be found at www.par-
entsmedguide.org along with other information about antidepressant use in children.
Since the original announcement in 2004, there has been significant controversy and concern about
how to address the black box warning in clinical practice. While there does appear to be a small
increased risk of suicidal thoughts and behaviors, there are also great risks associated with untreated
mental illness. Suicide remains the third leading cause of death in youth [13]. Since the black box
warning was implemented, the rate of antidepressant prescribing in children and adolescents has
declined and at the same time the adolescent suicide rate has gone up for the first time in over 10 years
[14]. In clinical practice, patients must be given appropriate information about these risks, and the
potential risks versus benefits must be weighed carefully when deciding how to treat. When starting
Table 2 Selective norepinephrine reuptake inhibitors (SNRIs) and miscellaneous medications

Primary metabolism Half life parent/
Pediatric and active CYP450 system active
Name indication Starting dose Max dose metabolites (AM) effects metabolites
Duloxetine None 30 mg/day 120 mg/day 1A2, 2D6 2D6 moderate 12 h
(Cymbalta) inhibitor
1A2 weak
inhibitor
Venlafaxine None 37.5 mg/day 375 mg/day 2D6 2D6 weak Parent: 5 h
(Effexor) inhibitor
AM: O-desmethyl- 3A4 inhibitor AM: 11 h
venlafaxine
Venlafazine Er None 37.5 mg/day 225 mg/day 2D6 2D6 weak Parent: 5 h
(Effexor XR) inhibitor
AM: O-desmethyl- 3A4 Inhibitor AM: 11 h
venlafaxine
Dewvenlafaxine None 50 mg/day 50 mg/day Liver: minor 3A4 2D6 very weak 11 h
(Pristiq) inhibitor
UGT
Miscellaneous medications
Mirtazapine None 15 mg/day 45 mg/day 1A2, 2D6, 3A4 None 20–40 h
(Remeron)
Buspirone Anxiety 15 mg/day 60 mg/day 3A4 None 2–3 h
(Buspar) bid bid
an antidepressant in someone under 25 years of age, additional monitoring is suggested with close
follow-up as clinically indicated on an individualized basis. Some recommendations have called for
weekly appointments for the first 4 weeks, then every 2 weeks for the following 4 weeks. This is not
always possible due to scheduling issues, insurance coverage, and other logistical factors. Phone
check-ins can be used to partially address this and close coordination with other care providers who
see the patient more often can be helpful in monitoring during the early stages of treatment.
Serotonin Norepinephrine Reuptake Inhibitors
The SNRIs include venlafaxine (Effexor and Effexor XR), desvenlafaxine (Pristiq), and duloxetine
(Cymbalta). The SNRIs do not have FDA approval for any indication in children or adolescents.
However, some prescribers may choose to use SNRIs for children who have failed or not tolerated
SSRIs or when looking for a broader spectrum of receptor activity. Published clinical trials of SNRIs
for pediatric anxiety are few and support the efficacy of venlafaxine for social anxiety disorder [15]
and show mixed evidence for efficacy for GAD [16]. There are no studies of duloxetine or desvenla-
faxine in children, and therefore this medication will not be discussed in this chapter. Table 2 presents
the SNRIs, mirtazapine, and buspirone, along with their indications, starting and maximum dosing,
and details of their metabolism. Similar to the SSRIs, the SNRIs and mirtazapine take several weeks
to show clinical effects.
The primary pharmacological effect of the SNRIs is to prevent the reuptake of norepinephrine and
serotonin from the synaptic cleft, with less potent dopamine reuptake inhibition. Lower doses of
venlafaxine act primarily as an SSRI with norepinephrine reuptake inhibition occurring with higher
doses. At the highest doses, dopamine reuptake inhibition occurs. The half-life of venlafaxine is
about 5 h, and it is metabolized by the CYP-450 2D6 but does not appear to inhibit this or other
CYP-450 pathways to a clinically significant extent. Drug interactions are few with most reports
focusing on cumulative serotonin toxicity with combined use of venlafaxine with other serotonergic
medications [17].
Adverse Effects
Common adverse effects of venlafaxine include nausea, headache, insomnia (activation), dry mouth,
and sedation. Blood pressure monitoring is also suggested as elevations in blood pressure related to
the added norepinephrine reuptake inhibition at higher doses can occur. It is not uncommon for people
to experience discontinuation effects with the short acting form of venlafaxine. These can include
dizziness, nausea, stomach cramps, sweating, tingling in the extremities, and various unusual sensory
phenomena such as burning, itching, pins and needles, and electric shock-like sensations.
The SNRIs can cause similar side effects as the SSRIs, including sexual side effects. Management of
these is the same as outlined for the SSRIs. Serotonin syndrome is a possible adverse effect when ven-
lafaxine is combined with other medications that raise serotonin levels. Details of serotonin syndrome
and its management can be found in the SSRI section. The SNRIs carry the same warning label about
suicidality as the SSRIs and similar care should be taken when prescribing and monitoring them.
Tricyclic Antidepressants
Although the TCAs have been available much longer than the SSRIs, they are not considered first line
treatments for pediatric anxiety disorders due to their inconsistent performance in the few available
efficacy studies as well as their less favorable adverse effects profiles. Clomipramine is the exception.
Clomipramine has demonstrated efficacy for OCD and has an FDA indication in children, ages 10 and
older. Imipramine has an indication for nocturnal enuresis and has demonstrated mixed evidence of
efficacy in childhood anxiety disorders. The strong norephinephrine reuptake activity of some TCAs
(e.g., desipramine) has led to their use in the treatment of ADHD [18, 19]. Case reports of sudden
death on desipramine in the early in 1990s led to decrease use of TCAs [20]. Table 3 presents the
TCAs, their indications, starting and maximum dosing, and details of their metabolism.
The TCAs primarily inhibit the reuptake of norepinephrine, acetylcholine, and serotonin from the
synaptic cleft and less strongly inhibit reuptake of dopamine. In addition, all the TCAs block hista-
minic (H1), muscarinic, cholinergic, and alpha-1 adrenergic receptors, which accounts for many of
their nuisance side effects. TCAs vary in how strongly they inhibit one neurotransmitter as compared
to the others. Clomipramine, for example, is a stronger serotonin reuptake inhibitor than the other
TCAs. This may explain its unique effectiveness in OCD. In contrast, desipramine is a potent norepi-
nephrine reuptake inhibitor, which may explain its efficacy in ADHD and lack of efficacy in OCD.
One advantage of the TCAs over the SSRIs is their relative lack of significant inhibitory effect on the
P450 system [21]. However, they are extensively metabolized through the P450 system and thus
blood level and half-life can be elevated by concurrent use of TCAs with some SSRIs. Like the SSRIs
and SNRIs, it may take several weeks to see improvement on TCAs.
Table 3 Tricyclic antidepressants
Pediatric Primary metabolism and any Half life parent/active
Name indication Starting dose Max dose active metabolites (AM) CYP450 system effects metabolites
Clomipramine OCD (>10 years) 25 mg/day 3 mg/day for the 1A2, 2D6, 2C19, 3A4 2D6 inhibitor Parent: 32 h
(Anafranil) first 2 weeks, up
to 200 mg/day
AM: desmethylclomipramine AM: 69 h
Amitriptyline MDD (>9 years) 9–12 years: 1 mg/kg/day 9–12 years: 5 mg/ 1A2, 2D6, 3A4 1A2 inhibitor Parent: 10–26 h
(Elavil) kg/day, up to
Psychopharmacology of Pediatric Anxiety Disorders
200 mg/day
>12 years: 10 mg tid >125 years: AM: nortriptyline 2C19 inhibitor AM: 18–44 h
200 mg/day
2D6 inhibitor
Desipramine None 25 mg/day 300 mg/day 2C19, 2D6 2D6 weak inhibitor 12–27 h
(Norpramin)
Nortriptyline MDD (>6 years) 1–3 mg/kg/day tid–qid 150 mg/day 2D6 2D6 weak inhibitor Parent 18–44 h
(Pamelor) dosing
AM: 10-hydroxynortiptyline AM: 8–10 h
Imipramine MDD (>6 years) 6–12 years: 1.5 mg/kg/ 6–12 years: 1A2, 2C19, 2D6, 3A4 2D6 weak inhibitor Parent: 11–25 h
(Tofranil) day tid 5 mg/kg/day
>12 years: 30–40 mg/ >12 years: AM: desipramine AM: 12–27 h
day qd–tid 100 mg/day
297
Adverse Effects
Anti-histamine effects include weight gain and sedation. Anti-muscarinic effects include dry mouth,
blurry vision, constipation, and urinary retention. Anti-alpha-1 adrenergic effects include orthostatic
hypotension and dizziness. The TCAs vary in how strongly they block each of these, leading to
different relative side effect profiles. For example, nortriptyline has the least alpha-1 adrenergic effects
and causes the least orthostatic hypotension, and desipramine tends to cause less anti-muscarinic
effects than the other TCAs.
The TCAs also block sodium channels in the heart and brain. This accounts for the risk of cardiac
arrhythmias, cardiac arrest, and seizures in overdose. The cause of sudden death in children is not
known, but it is presumed that individuals vulnerable to cardiac arrhythmia when exposed to QTc
prolonging agents such as desipramine may develop malignant arrhythmias [20]. How best to screen
for the presumed cardiac vulnerability is controversial as EKGs and echocardiograms may not iden-
tify any vulnerability. At this time, it is recommended that a baseline EKG and thorough cardiac his-
tory of the child and family (focusing on vulnerability for arrhythmia, sudden death not due to coronary
artery disease, and nonvasovagal syncope) should be obtained before initiating a TCA in children.
Further testing may be necessary based on the results of the history and EKG results. Follow-up
EKGs should be obtained as clinically indicated for a given patient.
The TCAs carry the FDA black box warning regarding increased risk of suicidality in children,
teens, and adults under 25 years of age. As with the other antidepressants, this should be monitored
closely, especially when initiating treatment and when adjusting the dose.
Benzodiazepines
The BZDs, while indicated for treatment of adult anxiety and used by clinicians to treat children
and adolescents, do not have an FDA indication for pediatric use with the exception of pre-anesthe-
sia. In addition, there are limited data to support their use in youth. Despite the lack of an evidence
base, they are used clinically in the context of panic attacks and for acute situational anxiety such
as before medical procedures, performances, and before school in children with severe school
anxiety.
The primary action of BZDs is to bind to GABA receptors, potentiating the effect of GABA at these
receptors, thereby increasing GABA’s inhibitory effects in the brain. In contrast to the antidepres-
sants, whose effects develop over time and persist due to changes in receptor sensitivity, the BZDs are
only useful for the time that they are being used. Hence differences in the duration of action inform
the choice of agent in specific anxiety disorders. Shorter half-life BZDs, such as alprazolam, may be
more helpful in acute anxiety attacks. Longer half-life agents such as clonazepam would be a better
choice for persistent lowering of overall anxiety (see Table 4).
Adverse Effects
BZDs have prominent central nervous system depressant effects leading to reduced anxiety but also
sedation and occasionally disinhibition, which can include hyperactivity, impulsivity, and agitation.
Care must be taken when prescribing the BZDs to adolescents or patients known to abuse alcohol or
Table 4 Benzodiazepines and equivalent doses (dose ranges for pediatric anxiety reflect off-label use)
1 mg lorazepam Half life
Name Pediatric indication Dose range equivalentsa
Alprazolam None Adult panic: 0.5 mg 12 h
(Xanax) 0.5–3 mg pot id
3–6 mg ER po qd
Adult anxiety:
0.25 mg po tid, Max
4mg/day total
Clonazepam Seizures <10 yo or 30 kg: up to 0.1–0.2 mg kg/day 0.25 mg >24 h
(Klonopin)
>10 yo or 30 kg: up to 20 mg/day
Diazepam Muscle spasm, tetanus, For anxiety: 5 mg >72 h
(Valium) status epilepticus 6 mos–12 yo: 0.12–0.8 mg/kg/day div
po q6–8 h
>12 yo: 2–10 mg po bid–qid
Lorazepamb Status epilepticus, For anxiety: 1 mg 15 h
(Ativan) nausea, sedation 0.05 mg/kg q4–6 h, max: 2 mg/dose
Temazepam None 7.5 mg qhs for insomnia in adults 7.5 mg 11 h
(Restoril)
a
The amount for a given BZD that is equivalent to 1 mg of lorazepam—for example 0.25 mg of clonazepam = 1 mg
lorazepam
b
Lorazepam has no liver metabolism
drugs as BZDs can be lethal when combined with alcohol or other depressants. In addition, patients
develop tolerance to the effects of BZDs and have potential for dependence and abuse.
Buspirone
Buspirone is approved to treat anxiety in adults but not in children. There is evidence of effectiveness
for generalized anxiety in adults, but the one trial of buspirone in pediatric GAD is negative and
unpublished [22]. Given the superior efficacy of SSRIs, buspirone should not be considered a first line
agent for pediatric anxiety disorders. Given buspirone’s serotonergic activity, prescribers may use it
as an adjunct in individuals with a partial response to SSRIs, although there are no data to support this
use in children. The indications, dosing, and details of buspirone metabolism are included in Table 2.
Buspirone is a 5HT1A receptor partial agonist with both presynaptic and postsynaptic actions.
Buspirone has a delayed onset of action similar to antidepressants. Buspirone is metabolized by the
CYP450 3A4 system. As a result, it has drug–drug interactions similar to the BZDs.
Adverse Effects
Buspirone’s advantages over the BZDs are lack of risk for dependency and abuse, lack of withdrawal
effects, low overall side effect profile, and lack of interactions with CNS depressants. The most com-
mon side effects include headache, nausea, and dizziness.
Mirtazapine
Mirtazapine (Remeron) is approved to treat depression in adults but does not have an indication to
treat anxiety disorders in either adults or children. It should not be considered as first line treatment
for anxiety in children but could be considered if standard treatments fail. Because it is available as a
rapidly dissolving tablet, it can be considered in patients who have trouble swallowing pills and
because of its sedating side effects it can be considered for use in patients with sleep disturbance.
There is a single 8-week open-label trial of mirtazapine for treatment of social anxiety in 18 children
age 8–17, in which 56 % of subjects responded but 4/18 discontinued due to irritability and fatigue
[23]. The indications, dosing, and details of mirtazapine metabolism are included in Table 2.
Mirtazapine acts as an antagonist for alpha-2 adrenergic receptors and for serotonin 5-HT2 receptors.
Mirtazapine, like the other antidepressants, has a delayed onset of action. Mirtazapine is extensively
metabolized in the liver by CYP450 1A2, 2D6, and 3A4, and its levels could be affected by coadmin-
istration of other medications that either induce or inhibit these enzymes. Mirtazapine itself does not
act as either an inducer or inhibitor of CYP450 enzymes.
Adverse Effects
The most common adverse effects of mirtazapine include somnolence, dizziness, increased appetite,
weight gain, constipation, dry mouth, and nausea. Mirtazapine carries the FDA black box warning
regarding increased risk of suicidality in children, teens, and adults less than 25 years of age. As with
the other antidepressants, this should be monitored closely, especially when initiating treatment and
when adjusting the dose.
Evidence Base for Specific Disorders
The current evidence base for pharmacological treatments will be reviewed for specific pediatric
anxiety disorders. In the case of OCD, where this is a larger evidence base, this includes evidence for
primary pharmacological treatments and augmenting and experimental agents. For the non-OCD
anxiety disorders, including PTSD, the focus is on primary pharmacological treatments.
Obsessive–Compulsive Disorder
Primary Pharmacological Treatments
There are numerous RCTs, open-label trials, and comparison trials supporting the use of serotonin
reuptake medications as first line pharmacological treatment (with or without CBT) in mild to moder-
ate OCD and certainly as first line in the most severe cases.
The Pediatric OCD Treatment Study (POTS) is a moderately large (n = 112) multicenter, random-
ized, placebo-controlled trial comparing sertraline up to 200 mg daily, cognitive behavioral therapy
(CBT), CBT with sertraline, and placebo in children and adolescents 7–17 years old. All three active
treatment arms showed statistically significant improvement compared to placebo, and combined
treatment with sertraline and CBT (ES 1.4) was superior to both CBT alone (ES 0.97) and sertraline
alone (ES 0.67) [24]. While sertraline was generally well tolerated, the most common adverse
effects were insomnia, agitation, nausea, and tremor. Based on the results of the POTS I trial, it is
recommended that treatment for pediatric OCD consist of a combination of CBT and medication
when possible.
Following up on the results of the POTS I trial, a second trial was conducted to examine the addi-
tion of CBT to an SSRI in patients with a partial response to the SSRI treatment alone. POTS II is a
12-week RCT of 124 outpatient children and adolescents comparing SSRI alone, SSRI plus CBT, and
SSRI plus brief CBT instruction as part of medication management appointments. The SSRI plus
CBT intervention was superior to the other two arms of the study on all outcome measures. Among
subjects receiving SSRI alone, 30 % were considered responders compared to 34 % in the brief CBT
group and 68.6 % in the CBT group. Number needed to treat for the medication alone group was 25
compared to 3 for the two other groups [25]. The findings of POTS II further support the combination
of CBT and medication management in the treatment of OCD when it is possible.
An earlier industry-sponsored RCT also demonstrated efficacy of sertraline up to 200 mg/day over
12 weeks among 6–17 year olds (n = 187) with OCD [26]. During the 1-year open-label extension
phase of the study, 85 % of initial responders maintained their gains, and 43 % of initial nonresponders
became responders by the end of the study [27].
Other SSRIs including fluoxetine [28, 29], paroxetine [30], and fluvoxamine [31] have RCTs sup-
porting their efficacy for treatment of OCD.
A number of controlled trials support the effectiveness of clomipramine, a TCA, in OCD, as compared
to placebo and desipramine [32–34]. Most significant among these was a multicenter, double-blind, RCT
of 60 children and adolescents (age 10–17) treated with up to 200 mg daily of clomipramine over
10-weeks. Subjects in the treatment group showed a 37 % reduction in CYBOCS scores compared to 8 %
in the placebo group (p < 0.05). While clomipramine was generally well tolerated, the most common side
effects were dry mouth, somnolence, and dizziness. No clinically significant EKG changes were found,
but mild pulse elevations, drops in systolic blood pressure, and weight gain were present [32].
In clinical practice, a variety of agents have been tried in combination with clomipramine for treat-
ment-resistant OCD patients. Of these, the combination of fluvoxamine and clomipramine is notable.
Fluvoxamine uniquely inhibits the conversion of clomipramine to desmethylclomipramine, thereby
increasing blood levels of the serotonergically active parent compound in the blood and reducing the
level of the almost exclusively noradrenergic effects of desmethylclomipramine. Such augmentation
strategies require great care with close monitoring of clomipramine/desmethylclomipramine blood
levels and periodic EKGs. Other SSRIs such as fluoxetine and paroxetine (and sertraline to a lesser
extent) when used in combination with clomipramine may actually increase the level of the noradren-
ergically active desmethylclomipramine and may not be as useful in reducing OCD symptoms. Other
medications have little or no effect on clomipramine metabolism (e.g., citalopram and escitalopram).
Patients with OCD and comorbid tic disorders, ADHD, and ODD may not respond as well to SSRI
treatment [35–37]. Other medications and behavioral treatments for these comorbid disorders may be
needed for optimal outcome. Patients with comorbid tic disorders may show more improvement with
the addition of an antipsychotic [38].
Augmenting and Alternative Agents
Despite the evidence supporting use of SSRIs and clomipramine for OCD, a substantial portion of
patients with OCD will not respond to monotherapy, will have an incomplete response, or not tolerate
antidepressant medications [32, 37, 39]. As a result, a variety of agents have been suggested and/or
tried as possible augmentation strategies. The augmentation strategies focus either on potentiation of
serotonin reuptake by using a second medication with serotonergic agonist activity (e.g., a second
serotonin reuptake inhibitor, lithium, or inositol) or by modulating the activity of other neurotransmit-
ters such as dopamine (e.g., antipsychotics) or glutamate [e.g., riluzole and N-acetylcysteine (NAC)].
More recently, there have been efforts based on our understanding of fear learning to improve the
outcome of CBT using d-cycloserine. With the exception of the addition of antipsychotics, the body
of evidence supporting the efficacy of any augmentation strategy in youth (or adults) is very small or
nonexistent; there are no controlled trials for augmentation strategies in the pediatric population.
At least nine double-blind placebo-controlled trials of antipsychotic augmentation of SSRIs exist
in the adult OCD literature, all of which demonstrated significant effect [40]. There is some evidence
that antipsychotic augmentation may be beneficial in pediatric OCD. One case series of risperidone
augmentation of an SSRI showed that all four patients demonstrated improvement in OCD symptoms
[41]. In an open-label trial of risperidone augmentation of an SSRI, 4/17 patients had a moderate
(>25 %) improvement in Y-BOCS scores and another 10/17 had slight (10–25 %) improvement; only
one patient’s score dropped from clinical to subclinical OCD during the 12 week trial [42]. A single-
case series looked at aripiprazole augmentation of SSRI for 39 adolescents with medication-resistant
OCD. Of the 39 participants, 29 (59 %) showed significant improvement in symptoms. Responders
were less functionally impaired at baseline but no different from nonresponders in overall clinical
severity. No participants dropped out due to adverse effects, and the most commonly reported adverse
effects were mild transitory agitation, mild sedation, and sleep disorders [43].
Inositol, a precursor in the phosphatidylinositol cycle, has been evaluated in small treatment trials
of OCD and for augmentation of SSRIs. A single double-blind crossover RCT of 13 adults using a
two-way repeated measures analysis of variance demonstrated no improvement versus placebo over
the course of 6 weeks at a dose of 18 g/day [44]. There have been no studies to date looking at inositol
in pediatric OCD, and other studies of inositol augmentation in adults did not show significant
improvement [45, 46].
Given the postulated role of glutaminergic dysfunction in the pathophysiology of OCD, riluzole, a
glutaminergic antagonist, was evaluated and demonstrated benefit in a single small (n = 6) open-label
trial for treatment of pediatric OCD, with four out of six subjects responding by week 12 at doses up
to 120 mg daily. No adverse effects led to discontinuation during the study, and all subjects chose to
remain on the riluzole after study completion [47]. There is also a single published positive case
report using fluvoxamine augmented by NAC for an adult subject with treatment-resistant OCD [48].
There are no published reports supporting NAC use in pediatric OCD. Other studies of both medica-
tions are underway and are appealing as possible options given the positive initial experiences and
low adverse event profile of NAC.
d-cycloserine is an N-methyl-d-aspartate (NMDA) receptor partial agonist that has been found to
facilitate fear extinction in animal models of anxiety [49, 50]. d-cycloserine has been evaluated in
adults as an augmenting agent to enhance fear extinction in behavioral therapy for anxiety disorders.
Specifically, it has been studied in adult SoP [51, 52], panic disorder [53], and OCD [54, 55] with
positive results for SoP and panic disorder. The adult OCD studies did not find statistically significant
differences. A single small (n = 32) double-blind placebo-controlled study compared CBT augmenta-
tion with d-cycloserine versus CBT plus placebo for treatment of pediatric OCD. Subjects received
DCS 1-h before exposure sessions. The study found no statistical difference between groups on pri-
mary or secondary outcome measures. There were no reported adverse effects [56].
Non-OCD Anxiety Disorders
The non-OCD anxiety disorders are a heterogeneous group consisting of SAD, GAD, SoP, panic dis-
order, selective mutism, and specific phobia. SAD, GAD, and SoP have overlapping symptomatology
(e.g., school avoidance behavior), are commonly comorbid, and have a positive treatment response
to CBT and antidepressant medications. As a result, many clinical trials group together children
and adolescents with GAD, SAD, and/or SoP and evaluate treatment effects on overall anxiety
severity. The data for panic disorder, specific phobia, school refusal, and selective mutism are
limited; therefore, this section will primarily focus on the treatment of GAD, SAD, and SoP
with briefer mention of the research on panic disorder, selective mutism, school refusal, and
specific phobias.
There are numerous acute, double-blind, placebo-controlled RCTs assessing medication treat-
ment of non-OCD anxiety disorders: some provide definitive evidence of efficacy whereas others
are small and evidence is equivocal. With increasing awareness that anxiety comorbidity is the rule
rather than the exception in children presenting to child and adolescent psychiatry clinics [8, 57–
60], the largest and most definitive pharmacological studies have assessed medication in children
with SAD, GAD, and/or SoP. Studies of subjects with a combination of SAD, GAD, and/or SoP,
which generally are larger and more rigorous, are discussed first followed by a section on diagnosis
specific studies.
Studies Combining the Three Disorders
The largest and most rigorous study of multiple anxiety disorders to date is the Child Adolescent
Anxiety Multimodal Study (CAMS), which evaluated sertraline up to 200 mg/day, placebo (double-
blind), CBT, or sertraline plus CBT (not blinded) in 488 children age 7–17 years presenting with
GAD, SAD, and/or SoP over 12 weeks. In addition, participants were allowed to enroll with comorbid
ADHD, PTSD, ODD, conduct disorder, and dysthymia. On all primary outcomes, CBT plus sertraline
was superior to CBT alone and sertraline alone (p < 0.001), which were equally effective, and all three
treatments were superior to placebo (p < 0.001). The effect size was 0.86 for combination therapy,
0.45 for sertraline, and 0.31 for CBT. The number needed to treat was 1.7 for combination therapy, 3.2
for sertraline, and 2.8 for CBT. Sertraline was generally well tolerated and there was no statistical
difference in rates of adverse events in the sertraline group versus placebo group. There was no evi-
dence of harm-related adverse events, and drop-out rates were similar between sertraline (17.3 %) and
placebo (19.7 %) groups. There were no suicide attempts by any subjects [8].
The Research Unit on Pediatric Psychopharmacology Anxiety Study Group multisite, double-
blind placebo-controlled trial studied 128 children age 6–17 years with diagnoses of GAD, SAD,
and/or SoP over 8 weeks who were randomized to fluvoxamine (up to 300 mg daily) or placebo [59].
Participants could have comorbid ODD and dysthymia but not ADHD, PTSD, conduct disorder, or
MDD. Participants in the fluvoxamine group showed statistically greater response (CGI-I <4) rates
(76 %) compared to placebo (29 %, p < 0.01). Adverse events were generally mild with abdominal
discomfort and increased activity level being more common on fluvoxamine than placebo.
Additionally, treatment gains were maintained for 94 % of subjects during the 6-month open-label
follow-up [61].
Similar to the RUPP study, fluoxetine, up to 20 mg daily, was compared to placebo over 12-weeks
in 74 children age 7–17 years. Participants were diagnosed with GAD, SAD, and/or SoP. Allowed
comorbidities included ADHD, PTSD, ODD, conduct disorder, and dysthymia. The fluoxetine group
showed significantly greater response rates (61 %) as compared to placebo (35 %) on a variety of
primary outcomes. By week 9 of the study, there was statistically significant difference between study
groups. Fluoxetine was generally well tolerated with abdominal pain being more common (44 %)
compared to placebo (22 %). Behavioral disinhibition was more common in the fluoxetine group
(n = 7) compared to placebo (n = 4), but this was not significant. Treatment gains were maintained in a
1-year open-label follow-up [62].
Social Phobia
A RCT (n = 80) of children age 7–17 with SoP compared fluoxetine alone, psycho-education alone,
and Social Effectiveness Training for Children (SET-C) combined with fluoxetine up to 40 mg daily
over 12 weeks. Children receiving fluoxetine plus SET-C showed the greatest response rate (72.7 %);
fluoxetine alone showed greater response rate (30.1 %) than children in the psychoeducation group
(6.3 %) [63].
A large (n = 322) 16-week multisite, double-blind placebo-controlled RCT of paroxetine (up to
50 mg daily) in children and adolescents ages 8–17 years with SoP demonstrated greater response
rates in the paroxetine group (77.6 %) as compared to children in the placebo group (38.3 %). As in
the other studies of SSRIs, the medication was generally well tolerated with mild to moderate side
effects including insomnia, vomiting, and reduced appetite [64].
A few trials of SNRIs and other antidepressants have been published. Venlafaxine XR (up to
225 mg daily) was compared to placebo in SoP among 293 children (8–17 years) over 16 weeks.
Response rates of participants on venlafaxine (56 %) were greater than those in the placebo group
(37 %). While most adverse events were mild to moderate (most commonly nausea, anorexia, weight
loss, pharyngitis, mydriasis); it is notable that three participants in the venlafaxine group developed
new suicidal ideation compared to none in the placebo group [15]. There is one small (n = 18) 8-week
open-label trial of mirtazapine in children with SoP, which found improvement in 56 % (10/18) of
subjects. However, four of the subjects discontinued due to adverse effects including fatigue and irri-
tability. There was also significant weight gain on the medication [23]. No other studies exist to date
regarding mirtazapine’s use in children with anxiety. Mirtazapine may be considered for use in chil-
dren with anxiety after a trial of other medications with more evidence supporting their effectiveness.
It may also be considered in patients with prominent sleep disturbance or weight loss.
Generalized Anxiety Disorder
Two double-blind RCTs evaluated venlafaxine XR doses up to 225 mg daily to treat GAD in children
age 6–17 over 8 weeks [16]. Pooled data (n = 320) identified greater response rates on venlafaxine
(68 %) as compared to placebo (47 %). Venlafaxine was generally well tolerated. Most common
adverse events included asthenia, pain, anorexia, and somnolence. A small double-blind trial (n = 22)
demonstrated the efficacy of a fixed dose of sertraline 50 mg daily in subjects age 5–17 years over 9
weeks [65]. An industry-sponsored trial of buspirone for children and adolescents with GAD did not
demonstrate greater response in the active as compared to placebo group. The study was not published
but described briefly in the buspirone product information [22].
Selective Mutism
Selective mutism is closely tied with social anxiety [66], has an early age of onset (i.e., preschool and
school age children), and is rare [67]. The efficacy of antidepressants for older children with SoP
informs the pharmacological approach to this young and often substantially impaired group of chil-
dren. To date, open trials and two controlled trials demonstrate promise for the SSRIs. A small
(n = 21) 9-week open trial of fluoxetine up to 60 mg/day in selective mutism demonstrated improve-
ment in symptoms among 76 % of subjects. Improvement was inversely correlated with age [68].
A small (n = 5) 16-week double-blind RCT (single-case research trial) of sertraline with selective
mutism showed a nonsignificant improvement in the active treatment group, but two of the five sub-
jects no longer met criteria for selective mutism after 10 weeks on sertraline (100 mg/day), and a
third subject was asymptomatic 20 weeks after the study [69]. A second slightly larger 2-week RCT
(n = 15) of children also showed improvement for the fluoxetine group, but the small sample size
precluded statistical significance and the short duration of the study may have precluded further
treatment effects [70].
School Refusal
The first study to address school refusal was a small (n = 35) 6-week trial of imipramine (up to 200 mg
daily) and behavioral treatment in children with school phobia. A greater number of children on imi-
pramine (81 %) had improved school attendance as compared to placebo (47 %). All of the children
on imipramine reported feeling much better after 6 weeks compared to 21 % of the children on pla-
cebo (p < 0.005) [71]. A subsequent attempt to replicate this study did not find imipramine effective
[72]. Another study compared CBT plus imipramine to CBT plus placebo in 24 depressed adolescents
with school refusal. The combination of CBT plus imipramine was superior to CBT plus placebo
(p < 0.001) over 8 weeks [73]. A single double-blind placebo-controlled trial compared clomipramine
(up to 75 mg/day) to placebo over 12 weeks in 51 youth with school refusal and found no difference
between groups [74]. A double-blind placebo-controlled 8-week trial of 24 school refusing children
and adolescent compared imipramine (up to 275 mg/day), alprazolam (up to 4 mg/day), and placebo.
No differences were found between groups.
Specific Phobia
The first line treatment for specific phobia is cognitive behavioral therapy; the evidence base for phar-
macotherapy is small. One double-blind RCT (n = 11) found paroxetine to be effective at doses up to
20 mg/day [75]. A small open-label trial of fluoxetine showed benefits in specific phobia. The partici-
pants had multiple comorbid anxiety disorders, and none of the specific phobia subjects had only a
diagnosis of specific phobia. However, global severity scores were obtained for each disorder and five
of six subjects with specific phobia showed significant improvement on fluoxetine [76].
Panic Disorder
Panic disorder is uncommon in children as it has a late adolescent–young adult age of onset [77].
There are no RCTs of pharmacological treatment of panic disorder in children. A single small (n = 3)
open case series of citalopram 20 mg daily in children with panic disorder symptoms and school
refusal found benefit [78]. A small retrospective chart review (n = 18) found significant improve-
ment in panic disorder symptoms for children and adolescents treated with up to 40 mg daily of
paroxetine [79].
Post-traumatic Stress Disorder
There are few controlled trials of medications in pediatric PTSD and all have shown no benefit to SSRI
treatment. A small (n = 24) 12-week double-bind, randomized, placebo-controlled trial comparing
trauma-focused CBT (tf-CBT) with sertraline up to 200 mg daily to tf-CBT plus placebo in subjects
found no difference between groups. Both groups showed significant improvement in PTSD symp-
toms [80]. Another larger (n = 131) 10-week multisite placebo-controlled trial of sertraline up to
200 mg daily in children and adolescents with PTSD also found no difference between active treatment
and placebo groups [81]. The most recent controlled trial was a brief (1-week) trial comparing
fluoxetine (5–20 mg daily), imipramine (1 mg/kg), and placebo in children with acute stress disorder
following burns, which showed no difference between groups [82].
However, a number of smaller uncontrolled studies have suggested possible benefits of antidepres-
sant medication in PTSD. Citalopram up to 40 mg daily demonstrated improvement in 67 % of par-
ticipants in a small 8-week open-label trial (n = 24) of children [83]. Imipramine up to 100 mg was
studied in one small (n = 12), prospective, randomized trial for acute stress disorder in pediatric burn
patients and was found to be helpful in ten subjects [84].
Medications other than antidepressants have been studied in pediatric PTSD. The first such group
is adrenergically active medications including alpha-agonists, beta-blockers, and alpha-1 antago-
nists. The alpha-agonists, clonidine and guanfacine, have limited data supporting their use in chil-
dren and adolescents with PTSD. There are no double-blind placebo-controlled trials of the
alpha-agonists in pediatric PTSD. However, a small (n = 7) uncontrolled trial of the clonidine patch
0.1–0.2 mg/day in pediatric PTSD found some benefit [85], and there is a single-case report of guan-
facine reducing nightmares in a 7-year-old girl with PTSD [86]. The beta-blocker propranolol (up to
2.5 mg/kg/day) was found to reduce PTSD symptoms in a small 5-week open trial in 11 youth with
PTSD as measured by the mean reduction in PTSD inventory scores (p < 0.0005). Propranolol was
generally well tolerated but mild drops in blood pressure and pulse rate limited the maximum dose
in two subjects [87]. There are no controlled trials of beta-blockers for treating pediatric PTSD. The
alpha-1 antagonist, prazosin, has been studied in adults with PTSD and found to be effective for
nighttime symptoms including nightmares [88–90]. There are three case reports of successful treat-
ment with prazosin treatment of these same symptoms in adolescents with PTSD [91–93] but no
controlled trials.
The second group of possible medications for treatment of PTSD is the atypical antipsychotics.
The only medications in this group with data on their use in pediatric PTSD are risperidone and
quetiapine. There are no studies supporting the use of olanzapine, aripiprazole, ziprasidone, or other
newer agents. Risperidone (mean effective dose 1.37 mg/day) was studied in a small case series of
18 boys with severe PTSD. There was a positive response in 15 of 18 subjects over the course of 16
weeks [94]. There is a single small (n = 6) 6-week open trial of quetiapine up to 200 mg daily in
adolescents with PTSD, which found reductions in PTSD symptoms as well as anxiety, depression,
and anger.
The final group of medications considered in the treatment of pediatric PTSD is the anti-epileptic
mood stabilizers. There are only two published trials of these, one for carbamazepine and one for
divalproex. A case series (n = 28) documented improved PTSD symptoms with carbamazepine 300–
1,200 mg/day. All subjects showed improvement, and 22 of 28 were asymptomatic at therapeutic
blood levels (10–11.5 mcg/mL) [95]. A single 7-week double-bind randomized trial of 12 male sub-
jects with PTSD and conduct disorder compared divalproex at either a high (500–1,500 mg/day, n = 6)
or low dose (up to 250 mg/day, n = 6) and found significant improvement in the high-dose group com-
pared to the low-dose group [96].
Despite the lack of controlled data, the current practice parameter from the Academy of Child and
Adolescent Psychiatry does state that clinicians may consider SSRIs and other medications in the
treatment of pediatric PTSD but with caution based on the lack of supporting studies. Generally
speaking, evidence-based psychotherapies for PTSD should be the first line treatment. Medication
should be considered earlier in the treatment course when a child presents with comorbid disorders
for which there is strong data supporting the role of medications [97].
Pharmacologically treating a child with an anxiety disorder has numerous components that must be
addressed by clinicians in a logical and stepwise manner. These include the pre-initiation evaluation,
the processed of initiating medication, dosing strategies, and next steps if there is lack of response to
treatment. Once there is a treatment response, focus shifts to maintenance treatment and ultimately to
consideration of medication discontinuation.
Prior to Initiating Medication
Practice guidelines from the American Academy of Child and Adolescent Psychiatry provide an out-
line of important steps in the evaluation and treatment of children and adolescents with anxiety disor-
ders and for the use of psychotropic medication in children and adolescents, some of which are
reviewed here [97–100]. First and foremost, a comprehensive diagnostic assessment should be per-
formed and should include information from the child, parents, and when possible from other impor-
tant people in the child’s life such as their teacher or therapist. A review of prior records should be
performed to assess prior interventions and their effectiveness. Standardized assessment forms and
interviews can be used when available to the clinician. A complete medical history must be taken to
rule out the possibility of medical problems causing psychiatric symptoms, to assess the baseline
health of the child before considering medication, and to assess whether further medical testing needs
to be done before medication can be prescribed to the child. An example would be obtaining an EKG
prior to initiating a TCA. While a physical exam is not essential, it can provide a baseline for future
comparison. Baseline laboratory testing, while not required, may allow for comparison later should
issues arise during treatment. If considering medication, such as the atypical antipsychotics, which are
associated with metabolic changes or other laboratory abnormalities, it is wise to always check labs
before initiating treatment. Finally, in addition to providing information on medication options, it is
important to keep in mind the evidence base supporting non-pharmacologic approaches and to offer
these to patients when appropriate and available. The AACAP has practice guidelines for OCD, anxi-
ety disorders, and PTSD, and the use of psychotropic medications in children is available on-line at
www.aacap.org for further detailed review.
Initiating Medication
When planning the pharmacological approach to an anxious patient, discuss the purpose and goals of
each treatment phase and the value of psychological treatments. During the acute phase of pharmaco-
logical treatment, the goal is to demonstrate very good response with minimal, if any, side effects.
Maintenance treatment focuses on maintaining response and enhancing functional capacity with com-
plete symptom remission. After remission and recovery, consideration can be given to a discontinua-
tion trial, which will require close monitoring to avoid any unobserved return of symptoms. Discussing
the phases of treatment will address common parent concerns about dosing (an effective dose and
duration is needed), expectation for outcome (children do very well with SSRI treatment), and how
long to treat before considering discontinuation (children do not necessarily have to be on medication
“forever”). Discussing the phases of treatment also prepares the patient and family for what to expect
and assures that they are prepared for the treatment trial.
When considering what medication to begin numerous factors may be taken into account includ-
ing the evidence base, effectiveness and tolerability of prior trials, patient or family concerns or
preferences regarding specific potential side effects, family history of response to medication, baseline
health status, and medical history. In addition, it is important to pay attention to the family’s attitude
about medication and directly address any concerns or negative feelings they have about medication.
If this step is skipped, it may lead to treatment nonadherence.
Once a medication is chosen, a patient and their parents must be provided with adequate informa-
tion to complete informed consent. This should include psycho-education about the child’s disorder
including symptoms, treatments, and prognosis. The name of the medication, alternative options,
starting and target doses, possible side effects, and expected benefits should all be discussed with the
family. It is also important to inform families how long it takes for medications to take effect. The
starting place with respect to medication in most pediatric anxiety disorders is an SSRI as outlined in
the earlier sections of this chapter. SSRIs are recommended as first line medications for both OCD and
non-OCD anxiety disorders by AACAP [98, 100]. There are no guidelines regarding which specific
agents to start. Clinicians need to make this choice based on the evidence base in combination with
all the other factors listed above.
Dosing
There are no specific guidelines for how to dose children with anxiety disorders, but it is generally
recommended that prescribers begin with low doses and adjust as clinically indicated based on the
patient’s response and any emergent side effects. When available it can be useful to follow the dosing
protocols found in clinical trials to avoid inadvertent under-dosing, waiting too long to assess effec-
tiveness, and considering alternative strategies. Benefit from an SSRI should be seen within 3–6
weeks, but maximum effect for a given dose may take 12 weeks or longer. A patient may continue to
make gains even after this time frame so clinicians must be cautious about reducing doses too soon.
OCD may take longer to respond to a trial of an SSRI than other anxiety disorders or depression.
Once a patient is on the maximum tolerated dose, improvement may continue for up to 6–12 months.
Educating parents about the therapeutic time course and reassuring them throughout the acute phase
of treatment is critical to assuring long-term adherence and the best outcomes.
Next Steps in Partial or Nonresponse
First and foremost, a partial or nonresponse should prompt the clinician to reevaluate the initial
diagnostic impression for accuracy. In addition, adequacy of dosing and duration of treatment should
be considered. Medication adherence should be assessed with the patient and family, and attention
must be paid to psychosocial factors that may be impacting the patient’s symptoms or adherence to
treatment.
If a patient fails an initial SSRI trial and the diagnosis is again found to be accurate, consider trying
a second SSRI. Evidence suggests that children may respond to a second SSRI trial. Following com-
pletion of the RUPP Anxiety Study, participants could participate in a 6-month open-label extension.
Subjects who were fluvoxamine nonresponders in the original study were offered treatment with
fluoxetine. Of the 14 who switched to fluoxetine, 10 (71 %) significantly improved over the course of
the follow-up study [62]. Addition of CBT should be considered if the patient is not already receiving
evidence-based psychotherapy as studies (discussed in detail in previous sections) such as CAMS,
POTS I, and POTS II have shown added benefit with combination of SSRI and CBT for OCD and
non-OCD anxiety disorders [8, 25, 26].
Augmentation strategies, which were discussed earlier in the section on OCD, can be considered
with persistent nonresponders, though the evidence base supporting these strategies is very small and
limited to OCD. Other reasons to consider adding a second medication are to treat any comorbid dis-
orders, to treat side effects of a medication (i.e., benztropine for extrapyramidal symptoms on antip-
sychotics), and when there is evidence that a particular combination of medications may be effective
for certain clinical presentations. An example of the last is the use of antipsychotics with SSRIs when
patients have both OCD and tics [39].
Maintenance Treatment
During the maintenance phase of treatment, patients should continue to show improvement in symp-
toms and overall stability. Visits to monitor medications may be reduced in frequency as clinically
indicated based on the number of life stressors for a given child and family, adherence to medication
and treatment, perceived reliability of the family, and adequacy of response to treatment. Coordination
with allied professionals such as the patient’s psychotherapist, pediatrician, and school during this
time can provide valuable interim feedback on how the patient is doing and may prompt a more
timely return to more frequent monitoring if an increase in symptoms is seen between regularly
scheduled visits.
Discontinuation of Medication
Deciding when to attempt a taper or discontinuation of medication has many components to it. Overall
life stressors must be taken into account along with duration of recovery, any side effects, or if the
medication has stopped working for the patient. For instance, it would likely not be a good idea to
attempt discontinuing medication just prior to a major stressful event in child’s life such as returning
to school for a school phobic child or leaving for summer camp for a child with separation anxiety.
There are limited data suggesting the optimal duration of treatment in the absence of major life
stressors. Data from clinical trials suggest that SSRI treatment for 1-year is both safe and effective in
anxiety disorders [101]. Given this, if a patient responds well to the acute phase of treatment, it is
appropriate to keep them on the medication for at least 12 months before considering closely moni-
tored discontinuation of the medication. It may be a good idea to wait as long as 18 months after
remission in OCD to begin discontinuation [102].
Any attempt to discontinue medication must be done carefully both to monitor for return of symp-
toms and to avoid withdrawal symptoms. The pace at which one can lower an SSRI without prompt-
ing withdrawal symptoms is very individual. Clinicians must go slowly and monitor closely. At the
same time, it is important to monitor for any return of symptoms. If the symptoms return in a milder
form, the patient may choose to remain on the lower dose or off of medication and work on their
symptoms in CBT. However, with any return of symptoms, strong consideration must be given to
restarting or increasing the medication back to maintenance levels. Educating the patient and family
about this process ahead of time is critical to assuring both a smooth discontinuation and prompt
return to treatment should symptoms recur during the taper. Once a patient is off of medication it is a
good idea to follow up with the patient for a period of time to monitor for recurrence of symptoms and
facilitate return to treatment, be that medication, therapy, or both. There are no specific guidelines as
to how long one should monitor a patient after stopping medication; this is left to the clinical judg-
ment of the prescriber.
Conclusion
SSRIs are the treatment of choice for OCD and the non-OCD anxiety disorders including SAD, GAD,
and SoP. While other medications including the TCAs and BZDs are used to treat anxiety in children,
the evidence base supporting their use is not as robust as it is for SSRIs. Although the outcome of TCA
studies is mixed, the findings for BZDs in pediatric anxiety disorders are uniformly negative
[103–105].
In contrast to the evidence base for OCD and the non-OCD anxiety disorders, there is a paucity of
data to inform clinicians on best approaches for youth with PTSD, panic disorder, and selective mut-
ism. With the exception of clomipramine for OCD treatment, TCAs and SNRIs cannot be recom-
mended as first line treatment of pediatric anxiety. SSRI failure due to incomplete response or side
effects should lead to a comprehensive reevaluation, increase in the intensity of psychosocial treat-
ments, and careful consideration of SNRIs and TCAs alone or in combination with SSRIs.
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Part IV
Special Topics
Anxiety in Children with Chronic Medical Illness
Patrick M. Kelly and Emily J. Frosch
Abstract Anxiety symptoms are common in chronically medically ill children and can have unique
issues which make their management complex. Anxiety can precede the medical illness, be a conse-
quence of the illness, or the two conditions may coexist with no clear chain of causality. As illustrative
examples, certain medical conditions particularly notable for their relationship to anxiety are dis-
cussed in greater detail. These include asthma, headache, inflammatory bowel disease, other forms of
gastrointestinal illness like irritable bowel syndrome, and cancer. For each of these conditions we
discuss the impact of preexisting anxiety as well as how (psychologically and biologically) these
illnesses can lead to anxiety. Psychotropic medication, psychotherapy, psychoeducation, family therapy,
group therapy, and improved psychosocial supports are all options for management and have varying
roles depending upon the particular medical and psychological concerns of a given patient. Addressing
this anxiety is critical, as evidence has shown that increased levels of anxiety in the child and in their
family can lower health-related quality of life, interfere with effective family functioning, and at times
even biologically worsen the course of the illness itself.
Keywords Pediatric anxiety • Mental health concerns in chronically ill children • Psychotropic medication
in medical illness
Introduction
The United States National Center for Health Statistics [1] defines a chronic illness as any illness of
“long duration” (persisting for >12 months, with impairment in daily functioning for >3 month/year
or hospitalization for >1 month/year). Chronic pediatric illnesses are on the rise. The point prevalence
of these conditions in children between the ages of two and eight years old increased from 12.8 % in
1988 to 26.6 % in 2006 [2]. The reasons for this increase in prevalence are multifactorial and
include increased incidence (e.g., obesity), increased length of survival (e.g., cystic fibrosis), and
decreased infant/early-life mortality from previously fatal conditions (e.g., AIDS) [2, 3].
P.M. Kelly (*)

Division of Child and Adolescent Psychiatry, Department of Psychiatry and Behavioral Sciences,
The Johns Hopkins Hospital, Baltimore, MD, USA
e-mail:pkelly14@jhmi.edu
E.J. Frosch
Division of Child and Adolescent Psychiatry, Department of Psychiatry and Behavioral Science,
The Johns Hopkins University School of Medicine, Baltimore, MD, USA
318 P.M. Kelly and E.J. Frosch
This chapter highlights the complexities of identifying and managing anxiety in youth with chronic
medical illness. General issues about the interaction between anxiety and chronic illness are discussed,
followed by a discussion of common manifestations and treatment of anxiety in select medical
disorders.
Developmental Considerations
Milestones Important to Understanding the Illness Experience
A child’s developmental level impacts his understanding of his illness, symptoms, and consequences,
which in turn affects anxiety levels. Pain is a common symptom of most chronic illnesses, and studies
have demonstrated age-related changes in abilities to rate pain accurately. Hicks et al. [4] found,
through the use of the Faces Pain Scale-Revised (FPS-R), that children begin to accurately rate their
pain sometime between the ages of 3 and 7, with a mean of 4.4 years of age. By “accurately,” the
authors meant that the self-report of painful experiences were congruent with the potential causes of
pain, the parents’ perception of pain, and the physiological (heart rate, blood pressure, etc.) and behav-
ioral (withdrawing from stimuli, etc.) manifestations of the reported pain. In a study of pediatric sur-
gery patients, Von Bayer et al. [5] found that most children overreported their pain before surgery but
accurately reported their pain subsequent to surgery. The authors theorize that some of this overre-
porting could be due to anticipatory anxiety, and it is only after the children have experienced true
pain that they become familiar enough with the sensations to rate it accurately. As such, children who
have experienced repeated pain throughout their life may be more precise, though no studies have
been performed to evaluate this supposition.
Understanding of the consequences of illness, including death, varies considerably with age, which
is likely to alter the impact of a chronic illness diagnosis on anxiety. Before the age of about 8 years
old, children do not understand that death is permanent [6]. This is likely to protect the young child
from experiencing the same level of anxiety as his/her parents who are well aware of possible mortality
when faced with their child’s diagnosis. Consequently, discussions about mortality held with younger
children with chronic illness may be far more difficult for the parents than for the patient.
The Impact of Illness on Development
Chronic illness brings with it not only episodic or persistent symptoms but also potentially recurrent
medical treatments. As a result, children may be isolated from some of the more normative experi-
ences of childhood and their development may subsequently follow a different trajectory [3, 7]. For
example, during adolescence, normal milestones such as having a romantic relationship, playing
sports, and going to social gatherings can all be delayed or missed due to chronic conditions. These
perturbations in the developmental tasks can lead to a sense of disconnect from peers and decreased
self-efficacy. One questionnaire used to evaluate these milestones is the Course of Life questionnaire
[8], given to young adults to evaluate their successful achievement of certain developmental tasks
necessary to exit adolescence. The five domains addressed (and an example of a question addressing
each) include the following: development of autonomy (going on vacation without parents), social
development with peers (belonging to a social group in high school), psychosexual development (first
time falling in love), antisocial behavior or acting out (being sent out of the classroom or punished in
school), and substance use/gambling (age of first drink). In a study of patients with chronic renal
failure in childhood, Grootenhuis et al. [9] found that young adults who achieved milestones such as
Anxiety in Children with Chronic Medical Illness 319
autonomy, social development with peers, acting out behavior, psychosexual development, and
substance use did so at a later age. The greatest delay was in psychosexual development. These delays
corresponded to lower quality of life (QOL) and a lower overall sense of health, particularly “mental
health” scores. This study replicated the results of an earlier, similar study by Stam et al. [10]
specifically evaluating survivors of childhood cancer. Further, since adolescence is typically defined
as a period of separation and individuation, dependence on external assistance from families or health-
care providers might interfere with the natural course of separation and identity development.
Comorbidity of Anxiety and Chronic Illness
The prevalence of anxiety disorders in medically ill children is 3–4 times higher than in the general
population, suggesting that anywhere from 7 % to 40 % of medically ill children are suffering from
impairing anxiety at any given time [11–13]. Anxiety disorders have been proven to worsen symptom
management, treatment adherence, medical outcome, and the ability of the child/adolescent to cope
with illness [14–16]. At times, the line between anxiety symptoms and illness symptoms becomes
blurred. For example, children with DSM-IV anxiety disorders and no complicating medical illness
often complain of somatic symptoms. The most common of these is restlessness (74 %), followed by
stomach aches (70 %), palpitations (48 %), muscle tension (45 %), sweating (45 %), and tremulous-
ness/shaking (43 %) [17]. Thus, for many pediatric providers, teasing apart these conditions can be a
challenge that may be even more difficult in children with chronic illnesses which may cause a myriad
of somatic symptoms. When discussing the interaction of anxiety and chronic medical illness, there
are multiple possible ways in which these two factors may combine, none of which are mutually
exclusive. The task of the physician is to conduct a complete assessment of the child and his family in
order to determine which pattern seems the most likely. This assessment will subsequently guide the
child’s treatment.
The first contextual framework in which anxiety and medical illness can interact includes cases in
which a preexisting anxiety disorder influences care of a medical illness. For example, young patients
with separation anxiety disorder have a difficult time undergoing procedures or hospitalizations in
which they are surrounded by strangers in the absence of their parents. As a result, the prospect of a
hospitalization may be more frightening than the illness itself for these children [18]. Generalized
anxiety can be a burden for medically ill children, as they may constantly fear the next hospitalization/
procedure and reassurance from their providers is unlikely to help. The child with obsessions about
germs may develop extreme fears while in the hospital. Specific phobias typically revolve around
procedures in ill children (oxygen masks or needle sticks). Socially phobic children may shy away
from forming relationships or interacting with peers or care providers, potentially leading them to feel
isolated and misunderstood. To enact effective treatment, it is essential for practitioners to obtain a
complete history of the child’s symptoms and feelings of anxiety in order to determine whether they
preceded illness onset. In assessing for preexisting anxiety, the clinician can begin with a family his-
tory, as a biological relative with an anxiety disorder may predispose the patient to the same. Premorbid
functioning, including early indicators of separation or social anxiety, can also reveal an underlying
proclivity to an anxiety disorder.
The second context includes the child’s psychological responses to a physical disorder including
the response to the medical diagnosis itself. For many children and families, this initial period is met
with a natural time of accommodation and adjustment that, with appropriate psychosocial support,
will come to its own natural resolution. For some, however, the adjustment is never successfully
navigated, resulting in psychological worries that can interfere with appropriate functioning in all
life domains [19]. When this occurs, it is unlikely that the patient will have a spontaneous resolution
without mental health intervention. Even a brief stay in an intensive care unit can psychologically
disturb children and their families; Stowman et al. [20] found that 25 % of these patients had symptoms
consistent with posttraumatic stress disorder after discharge. It is the responsibility of the physician to
discuss the psychological impact of the diagnosis and treatment with the child and family members to
determine whether any anxiety or mood symptoms are typical and may be expected to resolve or are
persistent and may require specific intervention. This is most clearly evaluated via the longitudinal
relationship between a provider and patient. One sign of concern is anxiety which seems to be gener-
alizing beyond the medical condition. Patients and families who are newly hypervigilant, socially
constricted, or overly concerned about aspects of life unrelated to illness (e.g., a mother who has never
previously been anxious develops sudden stage fright at the prospect of giving a presentation) may all
represent anxiety becoming more entrenched and deserving of dedicated treatment. This said, the
initial distressed reaction may give little information as to the prognosis for a later anxious condition,
so continued observation on the part of the clinician is critical.
The third category contains anxiety disorders that are a direct physiological consequence of the
medical illness. Various underlying medical processes can contribute to the presentation of anxiety in
a medically ill child. For example, increased blood carbon dioxide concentration, through conditions
such as asthma or cystic fibrosis, leads to increased symptoms of anxiety and can simulate a panic
attack [21]. Many systems can be involved in the generation of anxiety, including endocrine (hyper-
thyroidism, pheochromocytoma), cardiac (paroxysmal tachycardia, cardiac failure), or neurologic
(complex seizures, delirium) [22]. Table 1 contains a lengthy, though incomplete, list of conditions
that can directly produce anxiety symptoms. At times, the treatments for medical illnesses can them-
selves be direct causes of anxiety. For example, for asthma sufferers, both an asthma attack and its
treatment (albuterol) can lead to somatic sensations of anxiety [23]. Albuterol mimics the biological
effects of adrenaline, leading to increased heart rate and the “fight-or-flight” response. In patients with
gastrointestinal (GI) distress and cancer, some antiemetics, particularly procloperazine [24] or meta-
clopromide [25], can lead to akathisia, which resembles the physiological discomfort of anxiety and
can make the patient appear, and feel, anxious. For certain illnesses that are accompanied by exacer-
bations of symptoms, the physician can obtain regular ratings of anxiety from the child in order to
determine whether increases occur concurrently with increases in physical symptoms, either by direct
clinical interview or through standardized assessments. See Chap. 12 for questionnaires that assess
pediatric anxiety and that could be used for this type of monitoring.
Though not distinctly a fourth category per se, there is another important factor to consider in
childhood medical illness: the anxiety of the patient’s parents or caregivers. Though frequently over-
looked, this can often impact the successful treatment of the patient. Parents of children with multiple
types of illnesses, including such conditions as sickle cell disease [26], cancer [27], and chronic pain
[28], report more “chronic sadness” and anxiety than their peers. Caregiver anxiety has been shown
to be an independent predictor of worsened patient functioning, increased number and frequency of
symptoms [29], increased biological markers of illness [30], and increased acute care utilization [31].
Furthermore, some evidence seems to indicate that women are more prone to distress when faced with
illness in their child than men, regardless of their parental role in the family [32]. Walker et al. [33]
developed and evaluated the Illness Behavior Encouragement Scale (IBES), a child questionnaire ask-
ing how their parents respond when they report that they feel sick. In this study, parental affect was
associated with worsening functional performance and increased number of symptoms in their chil-
dren. Thus, evaluating parental worries and helping to alleviate them can lead to improved outcomes
for the child, as can brief screening for parental anxiety disorders including a family history.
When looking at a patient’s symptoms through this framework, it becomes easier for the clinician
to determine how the patient’s anxiety and medical problems interact. A family history of anxiety,
early anxiety symptoms, or characteristics of particular syndromes [like obsessive-compulsive disor-
der (OCD)] point to a preexisting or independent anxiety disorder. Anxious symptoms which peaked
after a particular diagnosis was given may indicate a psychological response to an illness, whereas
anxiety which seems conscribed to ill episodes or treatments may indicate a more biological response.
Table 1 Medical conditions which can cause anxiety
Neurological
Encephalopathy
Mass lesion
Postconcussive syndrome
Poststroke
Seizure
Vertigo
Endocrinologic disorders
Carcinoid syndrome
Diabetes mellitus
Hyperadrenalism
Hyperthyroidism
Hypothyroidism
Hypoglycemia
Pheochromocytoma
Metabolic
Hypercalcemia
Hypocalcemia
Hypomagnesemia
Hyperkalemia
Cardiac
Arrythmias
Congestive heart failure
Hypovolemia
Valvular disease
Pulmonary
Asthma
Hypercapnea
Hypoxia
Hyperventilation
Pneumothorax
Pneumonia
Pulmonary edema
Pulmonary embolism
Miscellaneous
Anaphylaxis
Hyperthermia
Pancreatic tumor
Porphyria
Systemic lupus erythematosus
Adapted from Cartwright-Hatton et al. [11]; used with permission
Familial difficulties may be determined by either the content or the process of taking a complete
history, and many clinicians who describe “frustrating” interviews are actually recognizing and expe-
riencing an aspect of the patient’s daily life which can have a tremendous impact on her psychosocial
functioning and ability to adapt to her illness condition.
In addition to a clinical assessment, there are standardized instruments which may help a clinician
better understand the medical and psychological health of their patient. One of the more general tool
sets, the Child Health Questionnaire (CHQ) [34, 35], is actually a family of self-report measures.
These tools are designed to be an analogue of the RAND-36 tool for adults and evaluate the child’s
overall physical well-being and the psychosocial impact of illness on his life. There is a parent version
for parents of children 5 and older and a child self-report designed for children 10 and older. The
shortest version can be completed in 5–10 min, while the longest version takes a half hour or more.
The Pediatric Quality of Life Inventory (PedsQL) [36] is another brief tool which has both parent and
child reports and even includes additional, disease-specific modules (for asthma and cancer, among
others). It should be noted that both the CHQ and the PedsQL must be purchased from the publishers.
In addition to general QOL measures, there are several illness-specific measures, including three
for asthma, six for cancer, and three for inflammatory bowel disease (IBD), among others (25 in all).
Davies et al. [37] completed a review and comparison of these various instruments, so providers treat-
ing children with particular conditions are advised to review her work to choose the best tool for their
practice based on patient age, time that can be devoted to completing a tool, parent vs. child instru-
ments, questionnaires vs. structured interviews, etc. Unfortunately, despite having illness-specific
measures, at the time of this writing there are no anxiety-specific measures targeted to the medically
ill child [19]. However, the Patient-Reported Measurement Information System (PROMIS) project
has at the time of this writing begun standardizing a retrospective assessment scale for anxious and
depressive symptoms during a medical hospitalization [38].
Specific Medical Conditions
Though anxiety and medical illness can be comorbid in many situations, there are certain illnesses for
which anxiety is a special concern. This may be because the illness is more likely to cause anxiety in
all persons, because the biological mechanisms of the illness or treatment may be particularly anxio-
genic, or simply because their prevalence makes them more likely to be seen by providers. We have
selected the following illnesses to discuss in more detail: asthma, headaches, IBD, functional gastro-
intestinal disorders (FGID), and cancer. For each condition, the authors will provide a brief descrip-
tion of symptoms as well as treatment, discuss the application of the above mentioned interaction
themes between anxiety and the condition, and discuss any treatments that specifically target anxiety.
At the time of this writing, an ongoing clinical trial is investigating the utility of a cognitive-behav-
ioral intervention strategy for patients with various types of chronic illnesses and their families to
preserve good psychosocial function and stave off anxiety [39]. This preventative model could pro-
vide significant advances in the field of psychosocial treatment of patients with chronic illness; how-
ever, most of the treatments discussed in this chapter will be illness-specific and targeted towards
patients already exhibiting anxiety symptoms.
Asthma
Billy was a regular in the pediatric emergency room. He was a small-for-his-age 9-year-old boy who
knew many of the nurses by name. His presenting complaint was usually the same—he had forgotten
to take his preventative inhaled steroid medications, leading to an asthma attack. His initial (rather
mild) wheezing would cause him to panic, making breathing even more difficult. During these attacks,
he would worry about going to the hospital or being intubated. Even if he was able to take his rescue
albuterol, he was frequently too overwhelmed to hold the medication in his lungs for any period of
time. Sometimes, the medicine seemed to make him even worse, as he would become red and covered
with sweat, eyes wide in fear. He and his mother were very close, and whenever she saw him suffering,
she became anxious herself which impeded her ability to help him manage his symptoms. Each admission
was a painful process—upon learning that he would have to be away from his family, Billy would wail
and cry, only worsening his breathing problems. Despite the pediatricians’ best efforts to emphasize
behavioral and medical interventions, they simply could not seem to get his debilitating asthma under
control. As a result, Billy frequently missed school. His mother had been told that he was failing the
3rd grade and couldn’t miss any more school, something that kept running through her mind as she
rode in the ambulance with her child back to the emergency room.
When Billy and his mother returned to his regular doctor, he recommended that they seek help from
a therapist who could teach Billy ways to slow down and control his breathing that could ultimately
keep him out of the hospital. Though Billy’s mother was skeptical, she took the doctor’s advice.
The therapist taught Billy some relaxation exercises involving tensing and relaxing his muscles and deep
breathing. The therapist even made a tape of these exercises that Billy and his mother could listen to
together at home. Not only did this help Billy to manage his symptoms but his mother had begun using
some of these tricks herself and was finding it easier to manage her own anxiety.
The National Center for Health Statistics reports that approximately 14 % of children in the United
States have been diagnosed with asthma, though the number continues to grow [40]. Male children
typically have a higher prevalence (17 %) than female (11 %) [40]. There is a large skew towards
minorities and persons who live in urban areas. Black non-Hispanic children have a higher rate (22 %)
than Hispanic children (17 %) or white non-Hispanic children (12 %) [40]. Furthermore, black children
with asthma have more poorly controlled symptoms resulting in more self-reported attacks and show
a higher rate of emergency department use than white children [40]. In 2005, asthmatic children had
12.8 million physician office visits and 1.8 million emergency room visits. Mortality from asthma is
increasing, though the absolute numbers remain low. In 1980, the rate of mortality from asthma was
1.7 per 1,000,000 children, which increased to 2.6 per 1,000,000 children in 2004 [40].
Asthma is a chronic inflammatory condition of the lungs. It is typically characterized by episodic
attacks during which the pulmonary airways constrict and prevent the flow of oxygen to the body. The
most common way to measure this is by using a peak expiratory flow (PEF) meter, which assesses
how quickly a person can move air into and out of her lungs. During an attack, the PEF decreases.
Symptomatically during this time, the child often feels a tightening sensation in her chest and throat
that can mimic panic. Asthma, like many illnesses, presents with varying degrees of severity. For some,
asthma is easily controlled with the correct medications. For others, asthma attacks can occur at any
time and for seemingly no reason. Medical management of asthma has two goals—to stop the current
attack and to prevent future attacks. Interrupting the current attack depends primarily upon broncho-
dilators, such as albuterol or ipratropium. Unfortunately, the effects of albuterol are quite similar to
those of epinephrine, an endogenous chemical the body uses to signal the fear response. Preventing
future attacks primarily relies on immunomodulatory and immunosuppressant medications such
as corticosteroids. These can be inhaled or taken as a pill. Regular use of these medications is critical
to staving off future attacks and can be particularly important to emphasize in adolescent patients as
Sadof and Kaslovsky [41] found that they tend towards greater medication nonadherence, which is
the number one risk factor for mortality in asthma [40].
Asthma and anxiety are highly correlated in children [42]. Among asthmatics, preexisting anxiety
conditions have been shown to be an independent risk factor for more severe symptom course and
more severe morbidity. Haby et al. [43] found that young adolescents with anxiety had significantly
more asthma symptom days and a more difficult and prolonged treatment course than their anxiety-free
counterparts. Though many believe this and similar findings to be solely due to anxiety interfering
with care adherence, some authors [44, 45] theorize that a heightened state of anxiety generally exac-
erbates immunologic reactivity, making a person more likely to have an asthma attack.
The psychological reaction to the diagnosis of asthma can lead to an increased amount of worry,
on the part of both the child and the family [46]. They may be hypervigilant about small changes in
their breathing, wondering if it is the sign of an impending attack. Furthermore, should children have
an asthma attack, hypoxia itself can trigger a panic-like response, as can the rescue medication
(albuterol), creating a cycle from which the patient has difficulty escaping. Caregiver anxiety has been
linked with increased inflammatory markers in asthmatic children [30], increased frequency and number
of hospitalizations [45], and lower overall patient QOL [47].
Although psychoeducational asthma management plans are recommended by the American
Academy of Pediatrics, few families receive them from their providers [41]. Among 130 young fami-
lies of young children with asthma, only 39 % reported receiving an asthma management plan from
their health-care provider, 57 % reported being taught how to monitor peak flow, and 52 % reported
being advised to change things at home or school to improve asthma management [43]. Family
involvement is also important, as anxiety symptoms in parents have shown to predict a worse asthma
course in their children [48]. Fiese et al. [49] present an excellent review of family responses to
asthma. Families who are able to come together and form new routines around asthma care (including
thoroughly cleaning the home environment and checking peak flows) feel more in control, become
closer as a family unit, and have fewer asthma and anxiety symptoms.
Regardless of the interaction between asthma and anxiety, children with both are more impaired
than with either condition alone. Richardson et al. [50] found that children with anxiety and asthma
had significantly higher rates of medical care utilization and hospital costs than those without anxiety.
Assessing for anxious symptoms in asthmatic children and their families has been helped by the creation
of standardized self-reports, such as the Youth and Parent Asthma-Related Anxiety Scale (YAAS and
PAAS, respectively). Both of these are available online [51] and can provide an excellent, rapid
method to screen large numbers of patients in a busy outpatient practice.
Once discovered, treatment of anxiety in children with asthma does not differ greatly from treat-
ment of anxiety in general [42]. Should a preexisting anxiety condition exist, treatment with SSRIs
may lessen the symptom burden and thereby improve the medical illness. Treatment with cognitive
behavior therapy has shown to reduce both psychological and medical symptoms in anxiety sufferers
with asthma [52]. Chiang et al. [53] evaluated relaxation breathing techniques combined with
progressive muscle relaxation (PMR). Providers directed children to sit comfortably in a quiet room
for 5 min, tense a group of muscles, such as those in the right arm, hold the contraction for about 8 s,
and relax the muscle group for about 30 s while breathing slowly. After a short rest, this sequence was
repeated with another set of muscles (15 sets in total). Through repetition, patients learned to recog-
nize the feelings associated with a tensed muscle and a completely relaxed muscle. This process and
the sequence of PMR exercises were recorded onto a CD, and one-page instruction sheet was pro-
vided to parents, who were taught how to coach their child to practice relaxation at home. Patients
were instructed to practice 30-min sessions, three times per week for 12 weeks until they achieved
some proficiency and could perform the exercise without the CD. This simple, rapidly taught inter-
vention required only 30 min to administer but reduced anxious symptoms and improved physiologic
measures of asthma. At the end of 12 weeks, the experimental group had fewer asthma symptoms,
used less asthma medication, had improved peak flow ratings, and reduced anxiety [53].
Headache
Katie had suffered from headaches since she was a young child. Her parents also suffered with
migraines, and so, as she got older, she was starting to accept that pain would simply be a fact of life.
She had been to numerous specialists, none of whom had yet found a medicine to prevent her head-
aches—the best she could get was temporary relief once they had started. Recently, she had been
using these types of medications even more frequently. During a recent visit to a neurologist, he sug-
gested that her headaches might be stress-related. He took a lot of time to explain that psychological
stress can cause a biological headache. She wasn’t imagining the pain, but rather it was directly
caused by physiologic changes in her body when she became anxious. It was true, she supposed, that
her headaches worsened during finals (which was particularly problematic since it caused her to miss
more school exactly when she needed to be there most). She began cognitive-behavioral therapy
(CBT) with a psychologist, learning ways she could reduce her stress. Not only were her headaches
fewer and less intense but overall she felt more confident.
Headaches are common in children. By age 15, nearly 75 % of children will report having had a
significant headache [54]. Generalized headaches can be divided into migraines, tension-type head-
aches (TTH), and chronic daily headaches (CDH). Migraine has been reported in 3.9 % of children
age 7–15 years, with increases from 1.7 % in 7 year olds to 5.3 % in 15 year olds [54]. On a monthly
basis, almost half of all children experience some form of headache, with up to 15 % of children suf-
fering from migraines [55].
A recent meta-analysis [56] of 33 papers investigating the burden of generalized headache in chil-
dren and adolescents found the morbidity to be significant, most consistently in terms of missed
school days (an average of 8.3 days per school year). Three papers [57–59] published by tertiary
headache care centers estimated an average of 32 days of schooling were “totally or partially affected”
by headache in a 3-month period (1 in 3 days). Many of these studies investigated total QOL, which
was significantly lower for children with headache vs. those without, based on various standardized
instruments. In one study of children asked to rate their current headaches, 17 % endorsed the state-
ment “this is terrible, I wish I would die.”
The American Academy of Neurology (AAN) [60] recommends that the evaluation and manage-
ment of recurrent headache in children be assertive, addressing the headache directly in each pediatric
visit, striving for complete remission as soon as possible, and minimizing the impact of any residual
symptoms on functionality and family life. The first step of management is to stop current headaches
with NSAID medications like ibuprofen, with triptans being prescribed only for resistant headaches
[61]. Subsequently, the focus expands to preventing future headaches with a variety of treatments.
Many of these medications have demonstrated efficacy in treatment studies of adult migraine but have
been expanded to use in children with various forms of chronic or recurrent headaches. Examples
include neurologic medications (antiepileptics, such as valproic acid and topiramate), psychiatric
medications (antidepressants, such as amitriptyline), cardiac medications (antihypertensives, such as
propranolol or amlodipine), and antihistaminic medications (such as cyproheptadine) [62].
Recurrent headaches in children are strongly correlated with anxiety. Kowal et al. [63] found that
children with anxiety at baseline are more prone to develop headache pain later in life. Knook et al.
[64] examined 134 children and found that headache was an independent clinical predictor of psychiatric
morbidity. In children with recurrent headaches, the level of anxiety has been reported to increase
from childhood to adolescence [65], and researchers have found that a history of childhood headaches
increases the risk for anxiety disorders in early adulthood [66]. A particularly vulnerable subset of
pediatric patients appears to be those who suffer from recurrent migraines. These patients have more
anxious symptoms and more missed days of school than their peers with other recurrent headache
varieties [67–70].
There may be an overriding biological association between anxiety and headache, particularly
migraine, which predisposes the individual, independently, to both problems. One strong candidate is
serotonin, which has been implicated in migraine [71] as well as anxiety. Studies have found that
5-hydroxyindoleacetic acid (5-HIAA) levels, a by-product of serotonin metabolism, are low in the
cerebral spinal fluid of both patients with anxiety disorders and patients who suffer from migraines
[72]. Additionally, an abrupt reduction in plasma serotonin has been associated with onset of migraine
[73], and intravenous infusion of serotonin was found to abort migraines [74]. This is also reflected in
the primary action of triptans, which reduce migraines by increasing cerebral serotonin.
It would seem, then, that treatment with antidepressant medications may be a way to alleviate
both anxiety and migraine pain. In the pediatric literature, there is evidence for the use of low-dose
amitriptyline [60, 75], though evidence for SSRI or SNRI medications has not yet been established.
In the adult literature, there are some supportive studies suggesting that fluvoxamine (Luvox) [76],
fluoxetine (Prozac) [77–82], and citalopram (Celexa) [83] may be as effective as amitriptyline,
though methodological problems (lack of a placebo control, small sample sizes, and underpowered
studies, or minuscule dosing of comparative medications) reduce the clinical utility of these results.
Among SNRI medications, a retrospective analysis [84] of 65 adult migraine patients receiving
duloxetine (Cymbalta) found a significant reduction in migraine attacks, and the effect was most
strongly seen in patients with comorbid anxiety. An open-label trial [85] of adult patients with migraine
and depression yielded similarly promising results, though both studies were small. Venlafaxine
(Effexor) has been evaluated in an open-label trial of 42 adult patients with migraine [86] and a retro-
spective analysis of 115 cases [87], both of which showed significant improvement in headache
attacks and days with headache after 4–6 months. A prospective, double-blind placebo-controlled trial
[88] showed fewer migraine attacks and lower use of analgesic medication in adult patients taking
150 mg of venlafaxine XR, and a prospective crossover trial [89] showed equivalent efficacy between
venlafaxine and amitriptyline, with significantly greater side effects on amitriptyline. In summary, for
pediatric patients, low doses of amitriptyline are effective in preventing migraine attacks and may
help reduce anxiety symptoms. More targeted therapies (SSRI, SNRI) are currently used only to treat
anxiety, though adult studies of SNRIs are promising for migraine prophylaxis as well.
Behavioral interventions are critical in the medical management of all forms of pediatric headache.
Regardless of any anxiety component, the AAN [60] recommends “biobehavioral” therapy for
prevention, which emphasizes adherence to treatment, psychoeducation, lifestyle changes to avoid
triggers, and coping strategies. Two particular modalities have been shown effective and at times
overlap—relaxation training and CBT. Relaxation training consists of teaching patients to voluntarily
control muscle tension through techniques including mental visualization and muscle tensing. Specific
protocols, such as PMR [90], are effective for children—a meta-analysis [91] examining all forms of
relaxation training found that they reduced the frequency of headaches by 32 % and the intensity of
headaches by 41 %. CBT seemed to be even more effective (though, admittedly, typically contains
elements of relaxation training), with a 49 % reduction in headache activity over seven studies.
Studies have also evaluated phone-based guided therapy [92], a CD-ROM computer system [93], and
Internet protocols [94] based largely on cognitive behavior therapy. All of these were found to be
effective in reducing both headache frequency and disability, even in the absence of measuring any
effect it may have on anxiety. Other treatments including acupuncture, chiropractic adjustments, hyp-
nosis, or TENS units are not supported by the AAN as viable treatment options for children [91].
Inflammatory Bowel Disease
Charley was admitted to the hospital for surgery. Unfortunately, despite all the medical management
possible, at the young age of 14 he was about to have most of his colon removed. On one hand, this
was an excellent development, as the surgery would likely fully cure the ulcerative colitis which had
ravaged his life. However, surgery is never benign and was accompanied by endless worries. His
mother had a diagnosed anxiety disorder for which she took antidepressants, and the patient himself
had always been perfectionistic and routine-based, so everyone was concerned as to how he would
handle this procedure. Initially, all went well—he was able to remain hopeful and focus on the positive
aspects of being, eventually, pain- and symptom-free. But after the surgery was another matter entirely.
His pain would not seem to respond to any amount of narcotics—he was on such a high dose at one
point that it actually threatened his ability to breathe. The team contacted psychiatry to discuss
whether his underlying anxiety may be contributing to this, whether he was misperceiving his actual
pain level. After seeing him, the psychiatrist thought that not only was this true but nothing was being
done to address the anxiety. Given the known relationship between the GI tract and the brain, and the
presence of serotonin receptors in both, the patient was started on the same SSRI as his mother, with
promising initial results, not only on his anxiety but also his pain.
Severe gastrointestinal illness like IBD, which includes ulcerative colitis (UC) and Crohn’s disease
(CD), can have a lifelong course and multiple psychiatric complications, including anxiety. About 1.4
million persons in America suffer from IBD. Incidence rates of CD are 3.1–14.6 per 100,000 patient-
years and for UC are 2.2–14.3 cases per 100,000 person-years [95]. Twenty-five percent of all IBD
cases are diagnosed prior to age 18, and 5 % are diagnosed before age 10 [96]. Cases which present
in childhood and adolescence are generally more extensive and aggressive at the time of diagnosis
and typically worsen during the first 5–7 years. These children also have a much higher rate of family
history of IBD (30 %, compared with 18 % for those cases presenting after adolescence) [97].
At its core, IBD is an overactive immunologic reaction to the digestive tract. This reaction causes
the tract to become inflamed, which can lead to various gastrointestinal effects [abdominal pain, con-
stipation, diarrhea, hematochezia (blood in stool)]. Associated symptoms include weight loss, malnu-
trition, anemia, fatigue, fevers, mouth ulcers, and joint pain or swelling. Should the inflammation
become chronic, it can lead to electrolyte abnormalities, ulcerations, fistulas, and dysfunction so
extreme as to require surgical intervention (a partial or full colectomy). Despite these serious and
diffuse symptoms, many patients are not immediately diagnosed with the condition. In a study of over
2,000 providers, Sawczenko et al. [98] found that the mean duration of symptomatology before diag-
nosis was 47 weeks (range 4 weeks to 7 years). In 10–20 % of cases, the abdominal pain was thought
to be primarily psychiatric in nature, and patients were diagnosed with depression, anxiety, or anorexia
nervosa with no suspicion for a physical underlying cause for their pain.
There are some differences in the symptomatology of ulcerative colitis and Crohn’s disease.
The hallmark of UC is bloody diarrhea [99], which typically results in an earlier diagnosis than CD
because of this characteristic symptom. The disease nearly always begins at the rectum and spreads
upwards, involving the entire colon in 10 % of patients (but slightly over half of those 10 % require
a full colectomy) [100]. It never spreads beyond the colon, and colonic resection of the affected por-
tion is generally curative of the illness (although comes with significant morbidity, such as postsurgi-
cal complications and potential use of a colostomy bag, and therefore is frequently avoided as long
as possible) [100]. CD, on the other hand, does not usually have any sort of characteristic external
symptom and so the diagnosis can be delayed [101]. In the pediatric population, the patient may
initially present for an evaluation of malnutrition, short stature, delayed puberty, fatigue, or even a
primary eating disorder (like anorexia) [102]. The illness can be present in any part of the digestive
tract, from the mouth to the rectum. CD typically involves multiple areas at once separated by unaf-
fected bowel, leading to the typical “skip lesion” pattern. Surgical interventions to manage this
condition are common (half of all CD patients require surgery at some point; of those, half will
require multiple surgeries) [103]. Unlike UC, surgery is not curative, as the disease can return to a
different part of the GI tract. Peripheral conditions, such as gallstones and kidney stones, are also
increased in CD [104].
The medical management paradigm in both CD and UC has shifted from symptom control to
mucosal healing [105], which is likely to result in prevention of disease progression, fewer complica-
tions, and reduction in the need for surgery [106]. In children and adolescents with CD, nutritional
therapy alone can sometimes be as effective as management with immunomodulatory medications
[107]. The dietary protocols are difficult, however, as they require forbearing all “real” food in favor
of sometimes unpalatable chemical formulas for a minimum of 8 weeks. As a result, lack of adherence
is the number one reason for treatment failures [108]. In both CD and UC, medications called mesala-
mines can reduce mild to moderate inflammation and alleviate pain. According to the American
College of Gastroenterology, in CD (and severe UC), the treatment of choice continues to be steroids
[109]. Confined disease in CD and UC can sometimes be treated with local steroids, but systemic
steroid use is common, even though these medicines cause their own significant side effects. Physical
side effects can unfortunately be somewhat synergistic with IBD and can include short stature, weight
gain, moon facies, and skin striae [110]. Even in low doses, steroids can directly produce anxiety as
well as mood changes and other alterations in mental status [3, 111].
IBD can be a difficult experience for a young person and their family. In CD, the symptoms are
frequently insidious and involve lifelong complications like short stature, which can make the child
feel different [112]. In a survey of 80 children (ages 7–19), Nicholas et al. [113] found that the most
concerning aspects of illness to children included negative body-image perceptions from the disease
process (short stature, weight loss, physical weakness), side effects from treatment (weight gain, acne,
a visible nasogastric tube), and embarrassment related to frequent use of public bathrooms and the
risk of encopresis. A separate survey by Mamula et al. [114] found that, as opposed to adults, the most
prominent concerns in children include delays in physical growth or pubertal maturation, shame asso-
ciated with fecal incontinence, and steroid-induced weight gain. These negative effects seem to
amplify as children age. College students who had been diagnosed with IBD as adolescents report a
lower overall QOL than younger peers with the same disease and feel poorly prepared to transition to
young adulthood [115]. A large summative meta-analysis by Ross et al. [116] of 12 studies (after a
further 266 were rejected for methodological problems) concluded that the overall health-related
QOL for children and adolescents with IBD is lower than their same aged peers, particularly in the
areas of self-esteem and social competence.
Up to 28 % of newly diagnosed IBD children meet criteria for an anxiety disorder, with lifetime
prevalence as high as 59–73 % [112, 117]. Though researchers have attempted to identify risk factors
for psychosocial dysfunction in IBD, the results are currently somewhat contradictory so it remains
necessary to screen all patients [118]. Anxiety can negatively impact the medical condition of IBD.
Reigada et al. enrolled a cohort of adolescents with IBD and compared those with significant anxiety
to those without. She found that adolescents with IBD and anxiety had significantly worse psychoso-
cial functioning and higher health-care utilization than their medically ill, but non-anxious, peers
[119]. A potential cause of this may be related to medical management of the illness, as higher levels
of anxiety in adolescents are correlated with lower medication adherence [120].
In adults, there is a clear biological association between higher levels of stress and more frequent
IBD flairs [121]. An animal model of IBD has demonstrated that inducing a depressive episode in
mice leads directly to flairs [122]. As with headache, there appears to be a close biological relationship
between IBD and anxiety, again through the commonality of the serotonin molecule. The neuronal
connections in the intestine are highly complex with about 400–600 million enteric neurons, which is
greater than the total of all sympathetic and parasympathetic ganglia combined and approximately
equal to the number of neurons in the spinal cord [123]. Serotonin is both a critical signaling factor in
the intestinal tract, regulating peristalsis and secretion, as well as a core neurotransmitter. In fact,
95 % of the body’s total amount of serotonin is present in the GI tract [124]. As discussed above,
serotonin is thought to be decreased in patients with anxiety disorders. Coates et al. [125] collected
biopsies from the GI system of 22 patients with IBD and compared them with normal peers. In the
affected patients, cells which secrete serotonin (enterochromaffin cells), mucosal serotonin concentra-
tion, and serotonin transporter concentration were all decreased. It appears that the chronic
inflammatory state itself decreases serotonin. This is consistent with studies finding reduced serotonin
and increased inflammatory markers in patients with anxiety and depression [126].
Family conflict and low family QOL have been positively correlated with pain, fatigue, and depression
in children with IBD [127]. Parents of children with IBD reported significantly less social support,
and mothers reported greater distress compared with parents of healthy children [128]. These interac-
tions can become a downward spiral in which the child’s illness and the family’s distress feed into
each other. Directly addressing parental anxiety may improve psychosocial distress, as positive affect
in mothers of adolescents with IBD is inversely correlated with the adolescents’ depression [127].
Treatment of the family could also improve illness trajectory. In study of 62 adolescents and their
parents, Hommel et al. [129] found that the mean rate of adherence with daily medications was 38 %
and was inversely correlated with family dysfunction.
Treatment for anxiety in children with IBD can take many forms. First and foremost, patient educa-
tion about the illness is critical. In a survey of 237 patients and parents by Casellas et al. [130], only
half described having “adequate” information, though all listed health-related information as extremely
important to their health-related QOL. A large, multisite, (700 patients) trial of adult patients by
Kennedy et al. [131] investigated a protocol to teach patients to manage their own symptomatology.
In fact, the intervention was specifically aimed at reducing health-care burden to providers, as it
focused primarily on creating alternative resources for patients so they did not feel the need to see the
provider as frequently. The patients were given a brief guidebook, “A Handy Guide to Managing
Ulcerative Colitis,” [132] and had a 2-hour consultation with a provider to obtain psychoeducation
and address questions. Despite the brevity of this intervention, at a time point of one year later,
patients reported fewer hospital and outpatient visits, improved QOL, and improved perceived “ability
to cope with their condition.”
Group psychoeducational interventions have also been examined [133]. In one intervention,
Grootenhuis et al. taught adolescents to implement an alternative, concurrent response (e.g., active
muscle relaxation) when facing a stressful, anxiety-evoking procedure (e.g., a venipuncture).
The protocol also discussed how to be a more active participant in treatment, including role-plays of
“approaching the physician,” and how to rate and describe pain accurately. The intervention resulted
in improved coping, greater feelings of competence, and overall improved health-related QOL.
A manualized protocol, Primary and Secondary Control Enhancement Therapy-Physical Illness
(PASCET-PI), has been evaluated in IBD children [134, 135]. The protocol involves nine modules
provided in a structured and hierarchical way. The first module concerns psychoeducation about the
illness. Modules 2–5 focus on building skills such as visualization, relaxation, and distraction to help
tolerate abdominal pain or distress. Modules 6 and 7 address negative and unhelpful thoughts about IBD
and its effect on the young person’s life. Module 8 helps the patient identify the most helpful of the above
techniques and create a personalized plan, and module 9 practices and reinforces it, with a view towards
anticipating and deflecting future problems. In a randomized controlled trial of 31 patients, there was a
greater reduction in anxious and depressed symptoms, improved feeling of control, and improved func-
tioning in the PASCET-PI group compared with a treatment-as-usual group [134].
Pharmacologic treatments targeting psychiatric symptoms are also effective in this population and
are frequently prescribed directly by the primary care team. In one study, children with Crohn’s dis-
ease were twice as likely as their disease-free counterparts to receive an SSRI and over four times as
likely to receive a tricyclic antidepressant (TCA) [136]. In adults, about 30 % of IBD patients have
taken antidepressant medications [137]. In a survey of 18 adult gastroenterologists, 78 % had pre-
scribed antidepressants for their IBD patients for the purpose of treating pain, depression, anxiety, and
insomnia [138]. Medications with evidence for efficacy in patients with IBD include bupropion, par-
oxetine, amitriptyline, and desipramine (though many are not considered first-line therapy in the
pediatric population) [139]. In animal models, treatment with fluoxetine and desipramine reduced
intestinal inflammation [140]. The reasons for this, the authors note, could be multiple. It may be due
to the intricate (and as yet poorly understood) brain-gut connection, in that improving anxiety some-
how alters the inflammatory cascade. Alternatively, it may be that increasing serotonin in the intestine
helps to alter inflammatory patterns. Due to the novelty of these results, antidepressant therapy has not
yet been evaluated in humans to assess efficacy in reducing inflammation, but they are promising.
Only one antidepressant, mirtazapine, is specifically not recommended for IBD and other inflammatory
conditions, as it increases the circulating levels of pro-inflammatory cytokines and may worsen the
underlying illness [141].
Functional Gastrointestinal Disorders
Annie is a 6-year-old girl who had been having attacks of severe abdominal pain since age 4. At that
time, her entire family suffered from a bout of viral gastroenteritis, but while the rest of the family
recovered, Annie continued to have intermittent symptoms. She has already missed enough school that
she may get held back—an eventuality that her high-achieving parents have difficulty accepting. Her
mother reports feeling frustrated and unsure of what else can be done to help her daughter. Despite
multiple visits to the pediatrician and to two gastrointestinal specialists over the past 2 years, nothing
could be found to explain Annie’s pain. Her mother, in desperation, had been researching online and
decided to try dietary restrictions. Annie was now lactose- and gluten-free, which initially seemed to
make a difference, but was currently having little impact. Recently, the pediatrician recommended that
Annie’s mother consult with a behavioral specialist to help her daughter more effectively manage the
pain. The mother scheduled an initial appointment, but, given their long road, her hopes were low.
First, the specialist started Annie on an antidepressant to address her anxiety symptoms and to
improve her intestinal function. Then, he worked closely with her, following a treatment protocol for
children with her condition that focused on teaching her how to manage her attacks. Her bouts of pain
were now less frequent, and, maybe more importantly, she felt less scared and out of control when she
did have one. She was back in school, and doing even better than she had before the pain started,
seeming more confident and more competent.
As opposed to IBD, FGID, otherwise known as recurrent abdominal pain (RAP) in children, is
characterized by pain or distress without structural or biochemical changes which could explain the
etiology or symptomatology. The first person to study this disorder, John Apply, began his research
in the 1950s and defined RAP as “3 or more episodes of abdominal pain of such severity as to inter-
fere with the child’s normal activity over a 3-month period without any clear etiology” [142]. In
1988, the Rome Foundation (http://www.romefoundation.org) was founded to further investigate
these phenomena, and still exists as an independent nonprofit organization dedicated to the evalua-
tion and treatment of FGID in children and adults. It has developed diagnostic criteria for various
categories and created an extensive screening questionnaire for children and adolescents. There are
a number of functional GI disorders, but for the purposes of this chapter, we remain focused primar-
ily on childhood FGID involving abdominal pain. FGID is subdivided into irritable bowel syndrome
(IBS), abdominal migraine, functional dyspepsia, functional abdominal pain (FAP), and FAP syn-
drome [143].
Abdominal pain in general is common, and functional GI disorders affect up to 19 % of children
and adolescents [144]. Up to 95 % of children with RAP do not have any explanatory physical
syndrome. There seem to be two main peaks of prevalence—the first occurs from approximately 4 to
6 years old, and the second peak occurs in early adolescence. This epidemiology was also seen in
studies of Sri Lankan [145], Malaysian [146], and Chinese [147] pediatric patients, so the phenomena
is not conscripted primarily to Western cultures. More females than males are affected, and there is a
greater prevalence among children of more highly educated parents [148]. In a large study by Baber
et al. [149], children with FAP were stratified according to Rome III diagnostic criteria. Forty-five
percent met criteria for IBS, 23 % for abdominal migraine, 15 % for functional dyspepsia, 11 % for
FAP, and 6 % for FAP syndrome. Approximately 2–4 % of pediatric office visits include complaints
of abdominal pain, and Shannon et al. [150] found that 8 % of middle and high school students had
reported seeing a physician for abdominal pain in the prior year.
Many children actually tend to underestimate the severity and/or number of pain episodes. In a
study by Chogle et al. [151] 63 children with RAP were instructed to maintain a daily pain dairy of
their abdominal pain for one month. At the end of that month, the diary was collected and the children
were separately asked to summarize their course over the study period. Sixteen percent of the children
were accurate, but the majority (53 %) underreported their number and severity of painful episodes.
The authors conclude that the majority of children underreport their number of painful episodes when
asked retrospectively, with adolescents underreporting more frequently than young children.
Many of the other conditions in this chapter have a distinct etiology that is important to know as it
may influence treatment options. FGID conditions are unique in that the etiology is, by definition,
unknown. One theory is that children develop RAP as a result of a traceable insult, such as a bout of
gastroenteritis [152]. Though the biological inflammatory markers seem to recede, the discomfort
continues to assert itself. It is thought that this inflammation leads to heightened gut sensitivity in
these youth, which can be recurrently activated. Parental suspicions about alternative etiologies, such
as food allergies, lack of dietary fiber, and lactose intolerance, are common [153]. However, attempts
to ameliorate symptoms with alternative diets (i.e., fiber supplementation or lactose-free diets) have
not proven globally beneficial and are not recommended by the American College of Gastroenterology
[154]. A small study of 22 children and adolescents enrolled for 10 sessions of yoga [155] showed
decreased abdominal symptoms and improved QOL, but further research is needed into complemen-
tary and alternative therapies for this condition, and they are not yet recommended treatments.
Anxiety is closely linked with FGID. In adults, a large prospective study seems to show that the
relationship is bidirectional (anxiety predisposes patients to develop RAP, but preexisting abdominal
pain also predisposes to the later development of anxiety symptoms) [156]. In pediatric patients, the
prevalence of anxious or depressive symptoms is far higher in 2–6 year olds with FGID (28.8 %) than
in the general population (10 %) [157]. Prospectively, a study of 28 children with functional pain
found that as these children entered adolescence and adulthood, they were significantly more likely
than controls to endorse anxiety symptoms and disorders, hypochondriacal beliefs, greater perceived
susceptibility to physical impairment, poorer social functioning, treatment with psychoactive medica-
tion, and generalized anxiety in first-degree relatives [158]. In a separate survey, most of the patients
with recurrent pain described themselves as “sickly” [159]. Parents of children with this condition
were almost twice as likely to have depressive or anxious symptoms, though in this study, causation
was not addressed [157]. Ramchandani et al. [29] divided parents of children with FGID into two
groups—those with a history of anxiety disorders and those without. Parents with anxiety disorders
reported higher ratings of anxiety in their children, more severe abdominal pain, more school days
missed due to pain, and less hopeful prognosis than their peers, regardless of the patient-reported
severity of symptoms.
Biologically, there may be a firm link between anxiety and FGID. In adult studies, markers of
elevated anxiety [increased serum cortisol, hypothalamic–pituitary–adrenal (HPA) axis dysregula-
tion] are also found in many patients with RAP regardless of their self-reported levels of anxiety.
A central brain structure involved in both processes is the amygdala. This region of the brain is known
to be involved in emotional regulation and emotionally informed information processing [160]. It also
controls the fear response. In laboratory experiments, fear causes colonic hypermotility in rats [161].
Additionally, the amygdala connects directly to the nerves collecting sensory information from the
intestine, so some authors posit that, in a fearful situation, the amygdala may misinterpret neutral
somatic sensations as painful [162]. This interaction represents only one part of the incredibly com-
plex brain-gut axis, which is thought to represent the central connections between somatic sensations,
colonic motility and secretions, and anxiety [163].
In medically treating FGID, first and foremost, physicians must rule out more dangerous medical
conditions. However, they must balance this with the fiscal and physical well-being of the patient, as
a study by the American Academy of Pediatrics [148] found that adolescents with recurrent pain have
far more medical tests, procedures, and even abdominal surgery than their peers, all of which include
costs and risks. Medications, such as antispasmodics and antacids, are not used without specific targeted
indications. Famotidine, an antihistamine, may reduce pain in children with dyspepsia. Peppermint oil
has one supportive study in reducing recurrent pain in children, but this has not been replicated [164].
Antinausea medications which interrupt serotonergic tone in the GI tract, such as alosetron, have
some evidence for efficacy in adults [165] but have not been studied in children.
Some trials exist for psychotropic medications in FGID patients regardless of their self-reports of
anxious symptoms. As in IBD (see above), there is some likelihood that patients who experience RAP
may have irregularities in their ability to regulate serotonin in their intestine [152]. Selective serotonin
reuptake inhibitors (SSRI) or other antidepressants may help regulate the serotonergic tone, which can
limit fluctuations in this tone and reduce both constipation and diarrhea [166]. Increasing GI serotonin
decreases visceral afferent signaling, a phenomenon associated with painful perceptions in patients
with FGID, and thereby may act as a peripheral analgesic [167]. In a trial by Campo et al. [168] involv-
ing 25 children and adolescents who had denied depressive or anxious symptoms, 84 % reported
significant improvement in their somatic symptoms after a 12-week trial of citalopram.
Because of the activity of norepinephrine in the GI tract, it may be that agents targeting this chemi-
cal in addition to serotonin [both TCA and serotonin norepinephrine reuptake inhibitors (SNRI)] may
be even more effective for this population. In adults, TCAs show good evidence for efficacy and are
the most thoroughly studied agents [169]. In children, one small study showed improvement in
abdominal symptoms [170], while another did not differ significantly from placebo [171]. A recent
further evaluation not only showed TCAs to be effective but that patient response persisted for an
average of 10 months, with some patients responding for nearly 4 years [172]. In adults, duloxetine
(Cymbalta) has been studied in one trial and found to improve patient ratings of pain, severity of ill-
ness, QOL, loose stool, work and family disability, and anxiety [173]. There has been a single case
report in the literature of a pediatric favorable response to duloxetine, though it has not been formally
evaluated in children [174]. In sum, there exists evidence for treatment of functional GI diseases with
SSRI medications regardless of the presence of anxious or depressed symptoms, though other agents
(TCA and SNRI), despite seeming mechanistically more effective, have not yet been thoroughly
investigated in children. Camilleri et al. [163] summarize some novel therapies which may prove
effective as they are more rigorously studied, including serotonin (and other neurotransmitter) modu-
lators, colonic secretion controllers, and anti-inflammatories.
Psychological treatment for anxiety in FGID can be difficult. The provider may be met with defen-
siveness, denial, or even hostility at the misperceived suggestion that patients’ pain is “all in their
head” or that they are fabricating this distress [175]. It is important to acknowledge that the pain itself
is real and distressing, regardless of its etiology. It can be helpful to frame psychotherapy and psycho-
tropic medications as helpful in coping with the anxiety that is intertwined with or the result of the real
physical discomfort that they are experiencing, even though the causality of the pain may still be in
question. Many of these children may be experiencing unintended, though reinforcing, consequences
of their pain such as being able to miss school days or having fewer demands at home [176, 177], but
this in no way implies that they are fabricating the pain artificially.
Psychotherapeutic treatment has traditionally revolved around self-regulating strategies to manage
the anxiety accompanying recurrent pain, including guided imagery and basic relaxation training
[178, 179]. These techniques have been shown to reduce the number and intensity of painful episodes
in children. Cognitive behavior therapy has been evaluated for treatment of pain and anxiety and
overall found to be effective [180, 181]. There is a manualized treatment, the treatment for anxiety
and physical symptoms (TAPS) protocol [182], specifically targeted at children with comorbid anxi-
ety and abdominal pain. Though provided by therapists, the goal of the protocol is to incorporate
techniques into the patient’s regular medical visits so that they can be utilized by mental health profes-
sionals in primary care settings. TAPS presumes that some of the symptoms of FGID are behavioral
in nature—that is, they are acquired over time through subtle reinforcement provided by the environ-
ment. By recognizing this, and practicing new, more adaptive behavior, patients are better able to
manage their condition. The TAPS program includes the following components: (1) information about
stress and its relationship to FGID, (2) self-monitoring of antecedent and consequent events associ-
ated with painful flare ups, (3) problem-solving strategies around stressors that aggravate symptoms,
(4) muscle relaxation exercises for lowering physiologic arousal and increasing a sense of mastery
over symptoms, and (5) cognitive restructuring for modifying faulty cognitions that underlie physio-
logic and emotional reactivity to pain (i.e., believing that the pain is an indication of a malign and
harmful internal process). When compared to a wait-list control, Warner et al. [183] found that 80 %
of children responded favorably to the TAPS program as indicated by reduced somatic discomfort and
reduced anxiety scales from both the patient and parents. These gains persisted through the end of the
study, 3 months after intervention.
There are various theories as to why and how CBT can be effective for FGID symptoms, as to
whether they address the symptoms of the condition itself, or rather they improve the patient’s psy-
chosocial well-being and thereby make the patient better able to tolerate the distress caused by their
GI condition. Interestingly (and perhaps counter intuitively, as CBT was in fact created to address
psychological distress), the former seems to be the correct theory. Lackner et al. [184] evaluated the
records of 147 patients with FGID randomized to a 10-week regimen of CBT, psychoeducation, or a
wait list. Two weeks after the intervention, CBT patients noted an improvement in gastrointestinal
symptoms, QOL, and overall psychosocial distress above the other two groups. However, using struc-
tural equation modeling, the authors found that improvement in GI symptoms was the core factor
upon which others depended. By that, the authors mean that the GI symptom improvement was not
dependent on improvement in QOL or in overall psychological distress.
Given the preponderance of evidence for increased parental psychopathology in terms of anxiety,
depression, and somatization, it is also important to engage the family in therapy. Studies of family-
based CBT techniques are quite promising [185–191]. The foundational ideas behind these tech-
niques are multiple. One idea is that parental psychopathology contributes to abnormal pain behavior.
The other, somewhat more complicated theory posits that the pain crises of children serve a behav-
ioral goal not only for the child but for the family as a whole. Duarte et al. [186] evaluated a family
therapy technique utilizing this theory. In this treatment, the consequences, both positive and negative,
of pain crises are explored. For example, if the child goes into a pain crisis and has to miss school, his
mother may be able to miss work and spend more time with their child. Once any unknown reinforc-
ers are brought to the forefront, families are better able to understand their role in the pain crisis and
shift from accommodating the crisis to assisting their child through it. The treatment focus then moves
to teaching specific skills to accomplish this goal, both cognitive (thought stopping, distraction) and
behavioral (increased physical activity, PMR). These are taught both to the child and to the family, so
that the family can aid in coaching the child through difficult times. The study showed that as few as
four 50-min sessions were effective at reducing self-reports of pain and of familial distress. Furthermore,
these sessions were led by general pediatricians, though the protocol was not manualized and there-
fore may be difficult for other physicians to adopt.
Oncology
Mr. and Mrs. Jones’ teenage son, Matthew, had recently been diagnosed with cancer. One month
prior, Matthew had been feeling more tired than usual and after some lab work was referred to a
specialist who made the diagnosis. Despite spending an hour with the doctor, Mr. and Mrs. Jones
realized that they couldn’t remember much of what they were told. They later described feeling “in
shock.” Over the subsequent weeks, Matthew and his parents tried to navigate the intense treatment
regimens that were prescribed while maintaining their hope that they would be successful. Matthew
seemed to take much of this in stride, but his parents struggled. They were not sleeping or eating regu-
lar meals, and Mr. Jones was finding it nearly impossible to concentrate while at work. Matthew’s
oncologist recommended that they see a therapist who could help them to manage their stress regard-
ing this new, terrifying situation. They initially felt selfish, taking time away from their son for their
own treatment, but eventually realized that they had to take care of themselves if they were to take care
of him. They began seeing a therapist in the hospital while Matthew received his chemotherapy to talk
about how the diagnosis had changed their lives, and though it took a number of visits, they began to
feel, in some ways, stronger as a family than they had ever been.
Cancer in young persons is still, fortunately, a low-prevalence condition based on absolute num-
bers. According to the American Cancer Society [192], about 15 children out of every 100,000 develop
cancer annually, though the incidence has been increasing slightly (0.6 % per year). In general, the
prognosis for pediatric malignancies is better than in adults. The 5-year survival rate for all cancers in
children is about 80 %. However, morbidity from cancer is quite high, in multiple domains. Up to
40 % of childhood cancer survivors develop neurocognitive problems, including problems of atten-
tion, memory, and information processing [193]. The biggest risk factors include central nervous
system cancers and radiation treatment [194].
Cancer in children is a heterogeneous group of disorders. Epidemiology, prognosis, and treatment
all vary significantly depending on the type of malignancy. However, there are similarities in how a
cancer diagnosis can affect a child and a family. In general, cancer treatment is difficult to tolerate.
It can include surgeries, radiation therapy, chemotherapy, or any combination of these. Chronic nausea,
fatigue, pain, infection, and ulcers can all interfere in a child’s normal development. Immunosuppression
can isolate a child from his peers, not only psychologically but also physically. Cosmetic side effects,
such as hair loss, can be difficult for children eager for peer acceptance. In fact, questions about hair
loss are frequently the first asked by adolescents upon learning their diagnosis [195]. Long-term
problems can include altered bone metabolism (leading to early-onset osteoporosis), cardiotoxicity/
cardiomyopathy, hypothyroidism, growth hormone deficiency, learning deficiencies, hearing loss,
and infertility [196, 197]. The use of treatment medications (corticosteroids, interferon, etc.) can
affect a child physically and emotionally, potentially leading to anxiety, depression, or neurocogni-
tive effects [198, 199]. All of the above can disrupt a child’s normal developmental trajectory, so the
oncologist must carefully balance the benefits of treatment with these severe side effects. Even after
recovery, a history of cancer treatment is associated with poorer psychosocial outcomes [200].
The most commonly reported mental health symptoms of pediatric cancer survivors are those of
posttraumatic stress, emerging in 13–16 % of survivors once they reach young adulthood [201, 202].
As many of these symptoms can persist or even develop beyond the acute phase of treatment, screen-
ing at each outpatient visit, a protocol evaluated and found to be practical by Kersun et al. [203] is
essential. As common as PTSD symptoms seem to be in cancer survivors, parents are at even greater
risk. Fifty-one percent of mothers and 40 % of fathers reported symptoms of acute stress disorder
1 week after diagnosis [204], and half of those continued to report symptoms consistent with PTSD
4 months after diagnosis [205]. These symptoms persist in many parents even after the completion of
successful treatment [206]. For some parents, posttraumatic symptoms seem to develop most pro-
foundly after treatment, with anxiety during treatment a strong predictive factor for mothers but not
fathers [207]. Greening and Stoppelbein [208] found that in a cohort of 150 parents with children
diagnosed with cancer, risk factors for developing anxiety and PTSD symptoms include avoidant
coping (substance use) and negative self-blame, while protective factors included enhanced social
support. Enhanced social support in the form of group therapy was also found to decrease anxiety in
the siblings of oncology patients [209].
To an extent, management of anxiety is embedded within cancer treatment. In 2009, the American
Academy of Pediatrics [196] officially recommended that all children diagnosed with cancer be
treated at specialized cancer centers, which all have psychosocial support built into the treatment
protocols. That said, some anxiety is refractory to this basic support and requires special attention.
Fortunately, behavioral therapy has been proven to lessen anticipatory (but not post-chemotherapy)
nausea and vomiting, reduce procedure-related anxiety, and potentially reduce self-reported pain lev-
els [210]. The National Child Traumatic Stress Network created a Pediatric Medical Traumatic Stress
Toolkit [211], primarily designed to aid the medical team in detecting and preventing PTSD in this
population (and other medically ill children). The toolkit contains a rapid screening assessment of
symptoms in children, including questions to ask the parents and the child. If any are positive, address-
ing concerns follows the D–E–F protocol: addressing distress, emotional support, and the family. Also
included are handouts for children and parents that discuss symptoms, normalize phenomena such as
not wanting to talk about stressful events, nightmares, and even reexperiencing, and give external
resources such as online support groups.
Studies have demonstrated that the mental well-being of the family has a direct effect on the well-
being of the child. A meta-analysis of studies of adolescents with cancer by Decker et al. [212] found
that social support from their families (particularly their mothers) was the most highly correlated
factor in improved health-related QOL. Robinson et al. [213] found that children whose parents are
suffering from anxiety are more likely to be distressed during treatment. As such, helping parents
manage their anxiety may be the single most helpful intervention a mental health clinician can provide
for the patient. In an effort to identify at-risk families, Kazak et al. [214] investigated the feasibility
and validity of the psychosocial assessment tool (PAT). This tool evaluates various domains of risk,
including resource availability, family problems, and social supports. In their study of 52 families
(47 treatment-as-usual controls), 72 % were not at risk, 24 % required further evaluation, and 4 %
were obviously in need of intervention. In a separate study [215], identification of difficulties with the
PAT was strongly correlated with higher rates of family treatment, indicating that once this need is
identified, resources are available to meet it. In one form of family treatment, called the Surviving
Cancer Competently Intervention Program-Newly Diagnosed (SCCIP-ND) [216, 217], the goal is to
prevent symptoms in parents before they start. It has four main components: joining highlights the
process by which the therapist and family work together to achieve therapeutic goals; maintaining an
interpersonal focus gives permission for the family to take a break from focusing solely on the patient,
emphasizing that a family member’s own ability to cope will be the very best thing they can learn to
help their child; normalizing the family experience reduces feelings of anxiety, anger, and isolation
and frames each person’s reaction to cancer as understandable responses under the circumstances; and
focusing on the family strengths enhances a family’s feeling competence despite the illness. The first
session ideally takes place within 1 month of the cancer diagnosis. In this session, the therapist dis-
cusses the diagnosis and presents the A–B–C framework for understanding the current situation,
focusing on adversities (the diagnosis of cancer), the families’ beliefs about these adversities, and the
relationships of these to their physical and emotional consequences. The family watches a 5-minute
video clip of other families participating in a similar exercise as modeling (this will occur in each ses-
sion). In the second session, the therapist introduces the idea of changing one’s thoughts to produce
different consequences. Families are coached to (1) accept the uncontrollable (“We could not have
prevented this illness.”), (2) change the controllable (“We can use skills to help our child cope with
procedures.”), (3) acknowledge and celebrate strengths (“We are a strong family and together we can
get through anything.”), and (4) focus on the positive (“We can support each other while acknowledging
that we have different ways of coping with our child’s illness.”). The third session focuses on support-
ing family growth in the future, as the diagnosis of cancer takes a more normalized role. The therapist
uses two metaphors, “the Family Survival Roadmap” and “Putting Cancer in its Place” [218], to help
caregivers recognize their beliefs about the family’s future. The Roadmap is a physical drawing of a
map (with obstacles, bridges, etc.) which helps families see their current relationship and the upcom-
ing future process of dealing with their child’s cancer. Putting Cancer in its Place helps the family
incorporate the diagnosis of cancer into the family life while diminishing its centrality. Kazak et al.
[216] found this intervention to be easily tolerable and to reduce anxiety and stress in the family.
Treating family anxiety with these protocols has also proven, in the long-term, to lower patient anxiety
and PTSD symptoms [219].
Conclusions
Anxious conditions are highly prevalent in medically ill children and can precede the medical illness,
be the consequence of the illness, or the two conditions may coexist with no clear chain of causality.
Family must always be kept in mind, as caretaker anxiety is an important but under-recognized com-
plicating factor in these cases. Certain medical conditions are known to be associated with higher
rates of anxiety, and thus, specific treatment protocols have been developed. Some protocols are
meant to be provided directly by the primary medical team, while others involve dedicated mental
health professionals. Medication, psychotherapy, psychoeducation, family therapy, group therapy,
and improved psychosocial supports have all been evaluated in these cases with varying success.
Anxiety in medically ill youth should always be evaluated and treated, as evidence has shown that
increased levels of anxiety can lower health-related QOL, interfere with effective family functioning,
and at times even biologically worsen the course of the illness itself.
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Anxiety in Children with Autism Spectrum Disorder
Heather Jennett, Roma A. Vasa, and Louis Hagopian
Abstract Autism spectrum disorders (ASDs) are a group of neurodevelopmental disorders

characterized by impairments in social and communication skills as well as restricted interests and
stereotyped behavior. Researchers generally agree that individuals with ASD are at high risk for anxi-
ety disorders. However, due to overlapping symptoms between ASD and anxiety disorders, the assess-
ment of anxiety in this population can be challenging. Further, the identification of appropriate and
effective psychosocial and pharmacological treatments for children with ASD significantly lags
behind these same efforts for typically developing children with anxiety disorders, leaving many
questions about how to best address anxiety in this population once it has been diagnosed. This chap-
ter aims to discuss the current knowledge related to the clinical presentation, prevalence, etiology,
assessment, and treatment of anxiety in children and adolescents with ASD.
Keywords Autism spectrum disorders • Anxiety • Behavioral assessment • Behavioral treatment

• Cognitive behavioral treatment • Pharmacological treatment
Case 1: Jessica is a 14-year-old girl with autism and severe intellectual disability. She has some sin-
gle words and uses picture cards to communicate. Her parents report that, at the sight of a dog, she
cries inconsolably, her body shakes, her eyes become wide, and she attempts to run away. At times,
Jessica’s fear has been so intense that she has run out into the street and has almost been hit by a car.
Jessica’s next-door neighbor has a dog, which makes it very challenging and time-consuming for her
to leave for school in the morning. When her mother prompts her to pass the dog to get in the car, she
hits and kicks her. Coupled with direct observation of Jessica’s response to dogs, behavioral inter-
views conducted with her parents ruled out the possibility that the purpose of such aggressive behav-
iors was to avoid going to school or to get attention from her parents. Based on this assessment,
Jessica was given a DSM-IV diagnosis of a specific phobia.
H. Jennett (*)
Director of Clinical Services, Little Leaves Behavioral Services, Washington, DC, USA
e-mail: hjennett@littleleaves.org
R.A. Vasa
Division of Child and Adolescent Psychiatry, Education and Training, Kennedy Krieger Institute,
Baltimore, MD, USA
L. Hagopian
Neurobehavioral Unit, Department of Behavioral Psychology, Kennedy Krieger Institute,
Baltimore, MD, USA
346 H. Jennett et al.
Case 2: Danny is a 10-year-old boy with a diagnosis of high functioning autism. He attends a
public school where he is placed in a mainstream classroom with 25 other students, one primary
teacher, and a teacher’s aide. According to his teacher, he is frequently rejected by peers due to his
immaturity as well as his intense preoccupations with dinosaurs. His parents report that he has no
friends outside of school aside from his older brother. He often makes statements that “he is scared of
his friends” and “no good at talking.” When a teacher suggests that he approach his peers, he
screams and runs away. Danny expresses fear of crowds and refuses to go anywhere without his par-
ents and his “safety” object—his favorite teddy bear. Based on interviews with Danny, his parents,
and his teacher, Danny was diagnosed with social phobia.
Overview of Chapter
Anxiety was described as a characteristic commonly seen in children with autistic disorder when it
was first described by Leo Kanner in 1943 [1]. Despite this, research and clinical practice related to
anxiety in this population is a relatively new undertaking, with an increase in studies over the past
decade. This may be due, in part, to the multiple conceptual and clinical issues related to disentan-
gling symptoms of anxiety from those of autism spectrum disorder (ASD) as well as the lack of clarity
as to whether anxiety should be conceptualized as a core feature of ASD or a separate and distinct
comorbid psychiatric disorder. This discordance amongst researchers and clinicians is likely due to
the symptom overlap between the two conditions. For example, symptoms such as social avoidance
and repetitive questioning are inherent features of both anxiety and ASD. When attempting to delin-
eate between disorders, developmental problems commonly seen among children with ASD, such as
deficits in verbal skills, cognitive abilities, and capacity to identify emotional states, limit the assess-
ment of this relationship. While clinicians can differentiate these symptoms through careful qualita-
tive assessments [2, 3], no standardized measure has been developed to successfully address this issue
[4]. Further, research on the identification of appropriate and effective psychosocial and pharmaco-
logical treatments specific to anxiety in children with ASD is still in its infancy. Between the increased
prevalence of ASD in general and the increased risk of anxiety disorders in this population, an under-
standing of how to assess and treat anxiety in children with ASD is critically needed.
This chapter aims to discuss the current knowledge related to the clinical presentation, prevalence,
etiology, assessment, and treatment of anxiety in children with ASD. Based on the proposed diagnos-
tic criteria for the diagnostic and statistical manual of mental disorders-V (DSM-V; see www.dsm5.
org), the term ASD will be used to refer collectively to autistic disorder, Asperger’s disorder, and
pervasive developmental disorder not otherwise specified (PDD-NOS), unless otherwise indicated.
The term HFA will refer to those children with high functioning autism (defined as IQ > 70) or
Asperger’s disorder.
Description of ASDs
ASDs are a group of neurodevelopmental disorders characterized by impairments in social and com-
munication skills as well as restricted interests and stereotyped behavior [5]. The phenotype of ASD is
markedly heterogeneous with respect to cognitive level, language level, and the type and severity of
associated medical and psychiatric comorbidities [6]. Approximately 50–75 % of children with ASD
have comorbid intellectual disabilities [7–9]. Seizures, gastrointestinal issues, and sleep problems are
also frequent [10]. Psychiatric concerns are common and include short attention span, hyperactivity,
aggression, self-injurious behaviors, and mood and anxiety symptoms and disorders [11, 12].
Anxiety in Children with Autism Spectrum Disorder 347
Autism prevalence has soared during the past decade with recent estimates from the Center for
Disease Control and Prevention (CDC) reporting that 1 in 88 children has an ASD, favoring males
with a 5:1 gender ratio [13]. Hypothesized factors contributing to this rising prevalence include
broader case definitions, improved diagnostic instruments, availability of services, and greater aware-
ness of the disorder [14].
The definition of ASD has gone through multiple reconceptualizations over the past several
decades. The current DSM-IV [1] classifies autistic disorder, Asperger’s disorder, and PDD-NOS as
part of a larger group of pervasive developmental disorders (PDDs). In order to be diagnosed with
autistic disorder, impairments must be observed across three domains—communication deficits,
social deficits, and the presence of repetitive and stereotyped behavior. Criteria for Asperger’s disor-
der are similar to autistic disorder except that there is no delay in language development. The diagno-
sis of PDD-NOS is a catchall term used to describe children who fulfill some but not all criteria for
autistic disorder or Asperger’s disorder. In the proposed DSM-V nomenclature, separate and distinct
diagnoses under the label PDD are collapsed into a single category—ASDs. Moreover, impairments
are observed across two domains, social-communicative and repetitive behaviors, in order to receive
a diagnosis of ASD (see Table 1 for further information about the diagnostic criteria across the two
manuals). The proposed criteria are intended to help clinicians diagnose a single disorder based on a
common set of symptoms rather than the presence or absence of a certain diagnosis (see www.dsm5.
org). The single disorder can be further specified by other clinical features including severity, verbal
abilities, and the presence of intellectual disability (ID). Research has found that the labels of autistic
disorder, Asperger’s disorder, and PDD-NOS are applied inconsistently across sites [15]. This shift to
a dimensional classification system, rather than a categorical one, is aimed at improving accurate
diagnosis and has been validated through field trials.
Overview of Anxiety in ASD
Research on anxiety in children with ASD is still in its infancy when compared to knowledge of anxi-
ety disorders in typically developing children. Leo Kanner was the first to describe and define ASD in
his paper entitled “Autistic Disturbances of Affective Contact” [1]. In this paper, he described 11
children who preferred to be alone, had difficulty with language and communication, engaged in
repetitive behaviors, and seemed to be experiencing anxiety when encountering a variety of environ-
mental events, such as loud noises, medical procedures, interruption of rituals, transitions, and novel
situations. With regard to anxiety, Kanner described these children as experiencing “major panic”
when encountering loud noises or moving objects and “grave emotional crisis” when undergoing
medical procedures [1, p. 245]. Further, he described their behavior as “governed by an anxiously
obsessive desire for the maintenance of sameness” [1, p. 245].
The DSM-IV also considers anxiety as an associated feature of autistic disorder, as indicated by the
statement, “there may be… excessive fearfulness in response to harmless objects” [5]. However, cer-
tain anxiety disorders should not be diagnosed in children with ASD unless “the disturbance does not
occur exclusively during… a pervasive developmental disorder” as indicated in the criteria for gener-
alized anxiety disorder and separation anxiety disorder, or the “fear or avoidance is not better accounted
for by another mental disorder (e.g., pervasive developmental disorder)” as indicated in the criteria
for social phobia. Despite this recommendation, there is some preliminary evidence that suggests that
anxiety disorders may be separate and distinct disorders in children with ASD. For example, LeCavalier
et al. used a confirmatory factor analysis to demonstrate support for the validity of several DSM-IV
disorders in children with ASD, including generalized anxiety disorder [16]. In addition, Wood and
Gadow cite some very preliminary evidence that has found the same genetic markers for anxiety in
typically developing children who have anxiety and children with ASD who have anxiety [3].
348
Table 1 Diagnostic criteria for autism spectrum disorder

DSM-IV criteria for autism Proposed DSM-V criteria for ASD
(I) A total of six or more items from (A), (B), and (C), with at least two (I) Persistent deficits in social communication and social interaction across contexts, not
from (A) and one each from (B) and (C) accounted for by general developmental delays, and manifest by all three of the
(A) Qualitative impairment in social interaction, as manifested by following:
at least two of the following: (A) Deficits in social–emotional reciprocity, ranging from abnormal social approach
1. Marked impairments in the use of multiple nonverbal and failure of normal back and forth conversation through reduced sharing of
behaviors such as eye-to-eye gaze, facial expression, body interests, emotions, and affect and response to total lack of initiation of social
posture, and gestures to regulate social interaction interaction
2. Failure to develop peer relationships appropriate to (B) Deficits in nonverbal communicative behaviors used for social interaction, ranging
developmental level from poorly integrated verbal and nonverbal communication, through abnormali-
3. A lack of spontaneous seeking to share enjoyment, ties in eye contact and body language, or deficits in understanding and use of
interests, or achievements with other people nonverbal communication, to total lack of facial expression or gestures
4. Lack of social or emotional reciprocity (C) Deficits in developing and maintaining relationships, appropriate to developmental
level (beyond those with caregivers), ranging from difficulties adjusting behavior
to suit different social contexts through difficulties in sharing imaginative play and
in making friends to an apparent absence of interest in people
(B) Qualitative impairments in communication as manifested by at (II) Restricted, repetitive patterns of behavior, interests, or activities as manifested by at least
least one of the following: two of the following:
1. Delay in, or total lack of, the development of spoken (A) Stereotyped or repetitive speech, motor movements, or use of objects (such as
language not accompanied by an attempt to compensate simple motor stereotypies, echolalia, repetitive use of objects, or idiosyncratic
through alternative modes of communication phrases)
2. In individuals with adequate speech, marked impairment (B) Excessive adherence to routines, ritualized patterns of verbal or nonverbal
in the ability to initiate or sustain a conversation with behavior, or excessive resistance to change (such as motoric rituals, insistence on
others same route or food, repetitive questioning or extreme distress at small changes)
3. Stereotyped and repetitive use of language or idiosyncratic (C) Highly restricted, fixated interests that are abnormal in intensity or focus (such as
language strong attachment to or preoccupation with unusual objects, excessively
4. Lack of varied, spontaneous make-believe play or social circumscribed or perseverative interests)
imitative play appropriate to developmental level (D) Hyper-or hypo-reactivity to sensory input or unusual interest in sensory aspects
of environment (such as apparent indifference to pain/heat/cold, adverse
response to specific sounds or textures, excessive smelling or touching of objects,
fascination with lights or spinning objects)
H. Jennett et al.
(C) Restricted repetitive and stereotyped patterns of behavior, (III) Symptoms must be present in early childhood (but may not become fully manifest until
interests, and activities, as manifested by at least two of the social demands exceed limited capacities)
following: (IV) Symptoms together limit and impair everyday functioning
1. Encompassing preoccupation with 1 or more stereotyped
and restricted patterns of interest that is abnormal either in
intensity or focus
2. Apparently inflexible adherence to specific, nonfunctional
routines or rituals
3. Stereotyped and repetitive motor mannerisms
4. Persistent preoccupation with parts of objects
(II) Delays or abnormal functioning in at least one of the following
areas, with onset prior to age 3 years: (1) social interaction, (2)
language as used in social communication, or (3) symbolic or
imaginative play
(III) The disturbance is not better accounted for by Rett’s Disorder or
Childhood Disintegrative Disorder
349
Differentiating ASD symptoms from those of certain anxiety disorders can be challenging because
of overlapping symptoms between the two conditions. In particular, there is significant symptom
overlap between ASD and social phobia, and ASD and obsessive-compulsive disorder (OCD). For
instance, symptoms such as preference for being alone, refusal to speak in public situations, and social
withdrawal are common to both HFA and social phobia [17]. A few studies of anxiety prevalence have
attempted to differentiate the social characteristics underlying these two conditions by modifying
common assessment measures. For example, in a study of HFA, Kuusikko et al. excluded all symp-
toms related to behavioral avoidance (e.g., “I try to avoid social situations,” “I leave social situations,”
and “I usually do not speak to anyone until they speak to me”) from the social phobia and anxiety
inventory for children (SPAI-C) [17, 18]. Additionally, the question, “It is hard for me to ask other
kids to play with me” was excluded since this symptom may reflect social skills deficits rather than
social anxiety symptoms. One other study removed items with symptom overlap between different
diagnoses [19], while another added in clarification questions to assess the child’s understanding of
the emotional words in the questions [11]. With these various modifications in place, the samples of
children with ASD were found to have clinically significant symptoms of anxiety independent of
ASD symptoms.
Similarly, repetitive and ritualistic behavior is a core feature of both ASD and OCD. Both disorders
can include symptoms of repetitive body movements, touching, ordering, and adherence to senseless
routines. In OCD, compulsions are often preceded by obsessions that are characterized as ego-dys-
tonic, intrusive, and unwanted [5]. In ASD, it is unknown whether obsessions precede compulsive
behavior. Further, many children with ASD often appear to enjoy and are comforted by their rituals
and overfocused interests (i.e., behaviors are ego-syntonic). Currently, very little is known about the
relationship between OCD and ASD, and researchers debate whether OCD should even be diagnosed
in individuals with ASD given the overlapping symptoms [20]. To date, two studies [21, 22] have
been conducted which compare repetitive behavior in individuals with ASD and individuals with
OCD. Both of these studies have found that the type of compulsions experienced by individuals with
ASD may be less sophisticated compared to those experienced by individuals with OCD. However,
both of these studies have limitations and more research on this issue is clearly needed.
Although researchers have begun to document the presence of different DSM-IV anxiety disorders
in children with ASD over the last decade, specific guidelines about how to make differential or dual
diagnoses are lacking, and current conceptualizations about overlapping symptoms vary across clini-
cians and researchers. Wood and Gadow suggest that anxiety disorders can only be considered as true
comorbid conditions if the anxiety disorder is “phenotypically and etiologically identical to the mono-
morbid condition (anxiety) in a typically developing individual (i.e., someone with no ASD diagno-
sis)” [3]. Otherwise, they suggest that professionals use of the term “co-occurring” to describe this
relationship.
Prevalence of Anxiety in ASD
Prevalence data on the presence of DSM-IV anxiety disorders and symptoms in children with ASD
vary widely across studies, with reported prevalence estimates ranging from 11 % to 84 % [4, 23, 24].
This wide range of prevalence rates likely results from the different methods used across studies with
respect to sample characteristics such as age, level of cognitive functioning, informant, and assess-
ment instrument used. One recent meta-analysis of 31 studies (n = 2,121) reported that almost 40 % of
youth under 18 years with ASD had at least one anxiety disorder [23]. Specific phobia was the most
frequently endorsed anxiety disorder (almost 30 %), followed by OCD and agoraphobia (17 %), social
anxiety disorder (17 %), generalized anxiety disorder (15 %), separation anxiety disorder (9 %), and
panic disorder (2 %). Posttraumatic stress disorder (PTSD) prevalence has varied with one study
reporting no cases of the disorder [25] and another reporting a prevalence of up to 17.4 % [26]. Of
note, most of the prevalence rates reported in this study are higher than the prevalence of anxiety in
typically developing children, reported to be less than 3 % in epidemiological samples [27]. In their
review article, MacNeil et al. also found a higher prevalence of anxiety in children with ASD as com-
pared to community samples of children without ASD as well as children with conduct disorder,
language impairments, Down’s syndrome, and mixed clinical diagnoses [4].
While the prevalence data represent a step forward in our understanding of anxiety in children with
ASD, several methodological issues constrain the interpretation of the data. First, most prevalence
studies of anxiety have been conducted in children with HFA or with school-age children and adoles-
cents with ASD from clinical samples, whereas few, if any, studies report on prevalence of anxiety in
lower functioning and younger children [28–30]. Second, the majority of the studies use instruments
to assess for anxiety that are validated in typically developing children but not validated for the ASD
population [4]. Third, anxiety is typically measured using a single informant, parent report. Few stud-
ies use child report because of the underlying belief that youth self-report of anxiety may be compro-
mised by difficulty recognizing and communicating emotions [31–35]. Finally, most studies have
small sample sizes, inadequately matched control groups and include heterogeneous ASD groups [4].
Despite these limitations, most studies seem to agree that children with ASD are at greater risk for
anxiety disorders than most other individuals.
Correlates of Anxiety in ASD
Several correlates of anxiety have been examined including IQ, ASD severity, ASD subtype, and age,
among which the most well-studied correlate is IQ [19, 30, 31, 36–38]. Several studies have reported a
positive correlation between IQ and anxiety, when anxiety is studied as a group of disorders [19, 30, 36,
38]. Researchers have hypothesized that children who are higher functioning are more likely to experi-
ence higher levels of anxiety due to greater insight and awareness of their differences as well as their
enhanced ability to communicate feelings of anxiety [38, 39]. These data however are not conclusive
as another study found no correlation between IQ and anxiety [40]. Children with ASD and ID have
also been shown to have higher rates of anxiety than individuals with ID but without ASD [28, 41].
Finally, a meta-analysis of the anxiety prevalence data indicates that higher mean IQ and anxiety are
correlated only for specific disorders, i.e., OCD and separation anxiety disorder, where as a lower mean
IQ is associated with a higher prevalence of anxiety in general and with social anxiety disorder [23].
The severity of ASD symptoms may also relate to anxiety. Mazurek and Kanne reported that chil-
dren with fewer ASD symptoms are at greater risk for anxiety [38]. Others however have reported that
greater ASD severity may increase risk for anxiety [19] or that ASD severity does not relate to anxiety
[40]. More research on these relationships is clearly needed.
A few studies have examined the issue of age-related differences in anxiety prevalence, but the
findings have been mixed. Using a cross-sectional design, Davis et al. examined age-related patterns
in anxiety symptoms from infancy to adulthood. The findings showed that anxiety increased from
toddlerhood to childhood, decreased through young adulthood, and then increased in older age (over
50 years old) [42]. Several limitations were noted, including the cross-sectional methodology, differ-
ent informants and instruments across the age groups, and lack of an adolescent group. Strang et al.
conducted a case-control study examining the influence of age (6–11 and 12–18 years) and IQ on
emotional symptoms in youth with HFA [40]. Results showed that levels of anxiety were unaffected
by age, IQ, ASD severity, or their interaction. Limitations of this study include its small sample size
and lack of control group. A recent meta-analysis found that anxiety was positively correlated with
age for anxiety disorders as a group and more specifically for generalized anxiety disorders [23];
lower mean age was associated with higher rates of OCD and separation anxiety disorder.
Aside from the correlates discussed above, there is little evidence that suggests other factors are
related to anxiety in individuals with ASD. Thus far, the prevalence data do not indicate a relationship
between anxiety in children with ASD and gender, race, or socioeconomic status. Additionally, very
little research has examined the relationship between anxiety and other psychiatric disorders in chil-
dren with ASD. In typically developing children, anxiety disorders frequently co-occur with depres-
sion and ADHD. In children with ASD, there is some evidence indicating that anxiety may be
associated with externalizing disorders [2, 19, 25, 43, 44]; however, further research investigating
these patterns is needed.
Etiology
There are currently no established etiological models that explain the development of anxiety in chil-
dren with ASD. Several hypothetical models that are beginning to gain empirical support are dis-
cussed below.
Neuropsychological
Weak central coherence theory, which was an early theory of ASD, may contribute to anxiety [45].
This theory postulates that children with ASD tend to overfocus on small details and have difficulty
seeing “the big picture” and that this underlying piecemeal approach may relate to differences in
visual attention [46]. This compromised ability to integrate multiple sources of information may lead
to confusion and distress in certain situations. Children may subsequently perceive certain situations
as scary [47]. The data on weak central coherence theory as a contributing factor to ASD however is
equivocal, with some data showing group differences [48, 49] on central coherence tasks between
ASD and typically developing children and others finding no difference [50, 51].
Neurobiological
A wealth of literature indicates that the amygdala plays a critical role in the pathophysiology of both
adult [52–54] and child anxiety disorders [55–58]. Together with influence from other brain regions
such as the orbitofrontal cortex and anterior cingulate cortex, this region regulates an individual’s
responses to incoming emotional stimuli [59–62]. Functional magnetic resonance imaging (fMRI)
data show that children and adolescents with anxiety disorders exhibit increased activation of the
amygdala compared to typically developing youth when performing a variety of threat processing
tasks, usually involving responses to facial expressions of fear and anger [63].
There has been enthusiasm for an “amygdala theory of autism” implicating this region in the
underlying social cognitive impairments of the disorder including difficulties with the perception of,
recognition of, and memory for emotion in facial expressions [64–66]. Empirical support for amygdala
dysfunction in ASD however has yielded some inconsistent findings. For example, several postmor-
tem studies report decreased cell size and increased cell density in this region [67, 68]. However, a
later study reported fewer neurons in the amygdala of individuals with ASD compared to controls
[69]. Volumetric studies have also reported inconsistent results with some data showing increased
amygdala volumes [70–74] and other data reporting decreased [75–77] or no difference [78, 79] in
amygdala volumes compared to control subjects. Finally, fMRI data report increases [80], decreases
[77, 81], or no differences [82–84] in amygdala function between individuals with ASD and control
subjects during tasks involving emotional displays. Methodological differences across the imaging
studies may account for the discrepant findings, including differences in the types of cognitive tasks
and the degree to which attention was manipulated [84].
Very few studies have examined amygdala function in relation to anxiety in individuals with ASD.
Juranek et al. examined a heterogeneous group of youth with ASD [85]. Positive correlations were
reported between increased total and right amygdala volume and scores on the child behavior check-
list anxious/depressed scale in children with ASD. In a study of adults with ASD, the level of self-
reported social anxiety as measured by the social avoidance and distress scale (SADS) was positively
correlated with right amygdala activation, indicating that the neural response to emotional faces in
ASD may be mediated by the degree of social anxiety [86]. Further research on the neural underpin-
nings of anxiety and its impact on social functioning is needed in children with ASD.
Genetic
Anxiety and depression are frequently comorbid and transmissible disorders [87, 88]. Therefore, high
rates of these disorders in family members of children with ASD, particularly first-degree relatives,
may confer risk for anxiety disorders in the offspring with ASD. Research on the relationship between
familial psychopathology and proband anxiety is important for early prevention, treatment of affected
individuals, as well as providing insight into potential genetic and environmental mechanisms of anxi-
ety in children with ASD [34].
The literature shows that parents and relatives of children with ASD have higher levels of anxiety
and mood disorders compared to family members of children with other developmental disabilities,
such as Down’s syndrome [89–91]. The majority of parents of children with ASD report the onset of
their emotional disorders prior to having any children [89–92] indicating that caregiver stress is not
the sole contributor to anxiety disorders in the parents.
Studies comparing the prevalence of emotional disorders in children with ASD and their relatives
are gradually emerging. Mazefsky et al. examined the prevalence of emotional disorders in a sample
of 17 adults with ASD and their first-degree relatives [92]. Results showed that 88 % of probands had
a mood or anxiety disorder. Higher rates of mood disorders were present in probands who had moth-
ers with depressive disorders compared to probands who had mothers without a mood disorder (80 %
versus 16 %). Associations between anxiety disorders in the proband and parent however were not
found due to the low rate of parental anxiety disorders. The results were viewed as preliminary due to
the study’s small sample size.
In a later study, Mazefsky et al. examined the relationship between emotional symptoms in adoles-
cents with HFA (n = 38) and their mother’s mood symptoms [34]. Anxiety and depression were present
in 39 % and 32 % of the adolescents, respectively. Maternal phobic anxiety and hostility were significant
predictors of adolescent anxiety. The researchers interpreted these data as preliminary due to the small
sample size as well as lack of structured diagnostic interviews to measure psychopathology.
A small body of research has explored the hypothesis that maternal mood disorders predict a
specific subtype of ASD that is characterized by higher cognitive functioning and the presence of co-
occurring internalizing disorders. DeLong proposed two “taxa” of ASD: one that is higher function-
ing, associated with comorbid anxiety and mood disorders, and linked to a family history of mood
disorder and another that is lower functioning and not linked to a family history of mood disorder
[93]. Cohen and Tsiouris found that recurrent maternal depression was associated with higher cogni-
tive and adaptive functioning, increased behavior problems, and an internalizing behavioral style in
offspring with ASD [94]. All mothers with recurrent major depression reported onset of their mood
disorder prior to having children, providing support for the hypothesis that depression in mothers of
children with ASD may result from genetic contributions rather than solely from caregiver stress.
Another study found that boys with high activity of the monoamine oxidase A (MAOA) gene were
more likely to exhibit fears and rituals as well as aggression if their mother had certain homozygous
compared to heterozygous MAOA alleles [95]. These preliminary findings suggest that certain com-
binations of maternal–child genotypes may influence the expression of anxiety in the child.
Environmental Factors
Wood and Gadow hypothesized that the interaction between ASD symptoms and several environmen-
tal stressors may increase risk for anxiety [3]. Specific stressors include increased academic demands,
expectations to focus on assigned activities rather than preferred interests, hypersensitivity to sensory
stimuli, and teasing and bullying. The transition to middle and high school can be a particularly stress-
ful time, especially for children and adolescents with HFA who are integrated in mainstream educa-
tional settings. This transition requires adjustment to a larger academic setting with a greater number
and diversity of students [96]. Academic demands suddenly increase and can be associated with
diminished environmental supports. Social interactions become more complex and individuals with
ASD may have difficulty navigating these challenges due to their core ASD impairments, including
communication deficits and limited theory of mind capabilities. As a result, ASD youth may experi-
ence academic deterioration, negative peer interactions, victimization, and social isolation, all of
which can increase risk for anxiety and depression [96–99].
Assessment
General Considerations
Multimodal and multi-informant approaches are generally recommended for assessing child anxiety
in typically developing youth and children with ASD [3, 4]. Anxiety is generally thought to include
behaviors from multiple domains, specifically behavioral, physiological, verbal/cognitive, and affec-
tive [100]. Multimodal assessment includes direct observation of behavior as well as self-report of
cognitions, affective states, and sometimes physiological responses evoked by feared stimuli [101,
102]. However, for individuals with ASD, cognitive and communication deficits may make the assess-
ment of cognitions, and affective and physiological states through self-report challenging, and in
some cases not possible [103].
Thus, multi-informant assessment is recommended. The tendency for clinicians to attribute symp-
toms of psychopathology to the cognitive deficits of the individual, a phenomenon known as diagnos-
tic overshadowing [104], makes accurate diagnosis of anxiety in individuals with ASD who also have
ID challenging. Additionally, parental reporting may be biased if a parent attributes certain symptoms
to anxiety or if the parent experiences his/her own anxiety [105–107]. Previous studies among the
general population [108, 109] and in children with ASD [35, 110] have also found low parent–child
agreement on specific measures of anxiety. Concordance between parent and teacher report of inter-
nalizing symptoms is also low [111]. Some authors have argued that parent report may be more valid
among children with ASD given children’s difficulties with emotional insight [19, 35], whereas others
have stressed the importance of obtaining data from multiple sources and contexts using different
types of assessment methods [111]. In summary, while multi-informant methods have been recom-
mended, issues related to informant selection have not yet been fully resolved.
Another issue that complicates the assessment of anxiety is determining whether behavioral
difficulties or negative emotional states are due to anxiety or some other type of problem. Great cau-
tion must be taken in inferring the presence of anxiety in this population based primarily on the obser-
vation of behavioral avoidance and apparent negative emotional states. Individuals with ASD may
display negative emotional behaviors and behavioral avoidance when encountering situations that are
simply non-preferred as opposed to aversive situations that induce fear. Functional behavioral assess-
ment of avoidant behavior can help make this distinction [112]. For example, demands to complete
academic tasks, removal of preferred items, or transitions from higher to lower preferred activities
have been shown to elicit problem behavior and negative emotional responses in this population. In
the case of noncompliance, avoidance may occur as a function of the individual lacking the necessary
skills, insufficient reinforcement to support the desired response, or the failure to discriminate what
response is expected. Avoidance and escape of academic demand situations through the display of
problem behavior is one of the more commonly observed operant functions of problem behavior [112]
in children with ASD. In the case of competing reinforcement, the individual may avoid a situation
because there is relatively more reinforcement associated with an alternative response that competes
with the one being prompted (e.g., the individual refuses to go to school because there is more rein-
forcement available at home) [113].
Despite these caveats, the presence of avoidance in combination with other indicators of fear
including fearful facial expressions and intense physiological arousal should alert the clinician to the
possible presence of anxiety. In addition to the intensity of the emotional response, the continued
display of fearful responses long after the eliciting stimulus has been removed might also suggest
anxiety. In contrast, avoidant behavior related to noncompliance or decrements in reinforcer density
may not be associated with extremely intense or lengthy displays of the classic indicators of fear, but
often quickly abate once the eliciting stimulus conditions are removed. Such observations in combi-
nation with other sources of assessment data (interviews, rating scales, and other observational data)
can be important to differential diagnosis.
Described below are methods for assessment that are aimed at overcoming some of these assess-
ment challenges. Methods that will be discussed include screening and diagnostic instruments, behav-
ioral interviews, direct observation of behavior, and physiological measures.
Screening and Diagnostic Instruments
In general, there are two categories of instruments available for the assessment of anxiety in individu-
als with ASD. These include (1) instruments designed to assess a broad range of psychopathology,
including anxiety disorders, in individuals with ASD and (2) instruments originally designed to assess
anxiety in typically developing individuals, which have been extended to individuals with ASD.
Instruments Designed to Assess a Broad Spectrum of Psychopathology

in Individuals with ASD
There are only a few instruments that have been developed specifically for the ASD population. These
involve both semi-structured interviews and rating scales. All of these instruments are in their infancy
and require additional study of their psychometric properties.
The Autism Comorbidity Interview—Present and Lifetime Version (ACI—PL) [11] is a semi-
structured diagnostic interview based on the Kiddie Schedule for Affective Disorders and Schizophrenia
(KSADS) [114]. It was modified to make it appropriate for use with individuals with ASD. For each
psychiatric disorder, additional screening questions are included which ask about common observable
features and presenting concerns of parents of children with ASD with each comorbid disorder.
Additional questions ascertain whether the child with ASD understands the emotion being assessed
before inquiring about specific symptoms. This instrument also has the ability to distinguish whether
impairment is due to the comorbid psychiatric disorder or due to the core features of ASD. Thus far,
the ACI—PL has found to be reliable and valid only for certain psychiatric disorders, with OCD as
the only anxiety disorder [11].
A few studies have used modified versions of other instruments designed for typically developing
children by removing symptoms that overlap between anxiety and ASD [17, 19] as well. The Autism
Spectrum Disorders—Comorbidity for Children (ASD—CC) [115] and the Baby and Infant Screen
for Children with Autism Traits (BISCUIT—Part 2) [116] are informant-based rating scales used to
examine comorbid conditions, including anxiety, in children with ASD. Parents or other caregivers
are asked to endorse items on a 3-point Likert scale. The ASD—CC was designed for children with
ASD ages 2–16, and the BISCUIT was designed for toddlers with ASD ages 17–37 months. Both
scales have good reliability [115, 116] and the ASD—CC has good validity [117].
Instruments Designed for Typically Developing Children and Extended

to Individuals with ASD
There are several well-established instruments developed to assess anxiety in typically developing chil-
dren. Although these instruments have been extended to individuals with ASD, none have been tested
for reliability or validity in this population. These instruments involve semi-structured interviews, infor-
mant-based rating scales, and self-report measures. The Anxiety Disorders Interview Schedule—Child
and Parent Version (ADIS—C/P) [118] is a semi-structured interview based on DSM-IV criteria. Its
reliability and validity are well established with typically developing children [119, 120]. Additionally,
there are many rating scales available for the assessment of anxiety in typically developing children, but
the most widely used include the Multidimensional Anxiety Scale for Children (MASC) [121], Revised
Children’s Manifest Anxiety Scale (RCMAS) [122], Spence Children’s Anxiety Scale (SCAS) [123],
and Screen for Child Anxiety and Related Emotional Disorders (SCARED) [124]. The latter two scales
also have parent versions available. Although these scales generally have good psychometric properties
for typically developing children [125], the use of self- report measures with children with ASD is cau-
tioned [34]. These instruments have been described in more detail in chapter “Assessment of Anxiety
Disorders: Categorical and Dimensional Perspectives.”
Behavioral Interviews
Interviews should be conducted with individuals with ASD to the extent possible with consideration
of the individual’s cognitive and language capabilities. Interviewing care providers (parents, teachers,
and support staff) may be the primary source of information about anxiety-related behaviors in some
cases. Information should be gathered on the nature of the anxiety response, the relevant antecedents
that occasion anxiety, as well as the consequences the behavior produces.
When interviewing care providers, it is important to distinguish between the respondent’s observa-
tion of events versus his or her interpretation of what the individual with ASD may be experiencing
and why. While care providers’ own hypotheses about the individual’s anxiety may be useful, the
clinician must also gather descriptive information and form his or her own hypotheses. In particular,
it is important to identify what particular situations or stimuli are avoided by the child, elicit escape,
and occasion negative emotional states suggesting anxiety, e.g., fearful facial expressions, crying,
shaking, and panic-like states. For young children and individuals with ASD who may be unable to
verbally express fear or their desire to avoid a situation, avoidance sometimes co-occurs with other
responses such as aggression, property destruction, and self-injury—particularly when initial attempts
to avoid or escape are ineffective [126, 127]. Although avoidant and escape responses are generally
maintained by negative reinforcement (i.e., escape or avoidance of the feared stimulus), it is important
to identify how care providers respond (or what other events occur) after the individual displays anx-
ious or avoidant behavior. Reactions on the part of care providers, including attention (in the form of
consoling the individual or talking about their anxiety) as well as access to preferred activities, can
inadvertently reinforce these behaviors.
The interview can also provide information about how the individual’s anxiety affects the care
provider. For many parents, observing one’s child in an anxious or upset state is often unpleasant and
anxiety inducing. Reacting in a way that reduces child anxiety (e.g., by permitting the child to avoid
the feared situation) also reduces the parent’s anxiety and thus reinforces these parent behaviors.
Understanding these interactions is important for understanding the broader context in which anxiety
occurs and has important implications for designing treatment. For example, different treatments
would be indicated in a case where the parent has a very low tolerance for his/her child becoming
anxious versus one where the parent has a higher threshold and shows little anxiety.
Direct Observation of Behavior
Direct observation of behavior can be more effortful and time-consuming than other methods of
assessment because the conditions that induce anxiety must be present. This is accomplished either by
observing the child in the natural environment or by simulating those conditions in the clinic setting.
Therefore, information obtained via interviews of the individual and care providers and findings
obtained from self- and other-report should be used to guide initial behavioral observations.
Determining whether the stimuli that induce anxiety can be precisely identified and presented in a
controlled manner is critical to designing formalized behavior observational procedures. For example,
some studies have described cases in which anxiety was elicited by specific stimuli such as water,
needles, or dental care [128–130]. Certain anxiety disorders, such as specific phobias, OCD, social
phobia, and separation anxiety disorder, are characterized by anxiety that is often elicited by a specific
stimulus or classes of stimuli. In these cases, presentation of the anxiety-inducing stimulus in a con-
trolled fashion may be possible. In other cases, however, the stimuli that occasion anxiety may be
difficult to identify or control. For example, individuals with generalized anxiety disorder may not be
able to identify specific stimuli that reliably elicit fear. In other cases, stimuli may be identifiable but
difficult to present and terminate with the level of control required in treatment—such as the behavior
of peers and certain internal stimuli (e.g., physiological sensations).
Naturalistic Behavioral Observation and Behavioral Monitoring
In cases where the anxiety-inducing stimulus cannot be readily presented in a controlled manner,
direct observations in the settings where the anxious behavior has been known to occur can be helpful
at various points in the assessment and treatment process. In cases where this is impractical (e.g., the
behavior is infrequent or unpredictable), enlisting care providers to monitor anxious behavior may
yield the most complete information. In contrast to self- and other-report measures, which involve the
retrospective reporting of behavioral patterns or tendencies, behavioral monitoring involves the obser-
vation and recording of discrete behaviors in real time or within a brief time frame. For example,
behavioral monitoring may involve a mother recording each time she observes her child checking to
see if a door is locked along with any observable antecedents and consequences for this behavior.
Parents can also provide ratings of subjective distress based on observable indices of affect such as
crying, trembling, or facial expressions. In addition to helping identify antecedents and consequences
during the assessment phase, data obtained using behavioral monitoring can be used to establish a
pretreatment baseline and evaluate treatment effects. Parental monitoring of anxiety in children with-
out ASD has been reported in several studies [131–133]. Although all of these examples involved
children without ASD, a similar type of monitoring can also be used with children with ASD and, in
some cases, may be the best source of data.
Behavioral Avoidance Test
In cases where the anxiety-inducing stimulus is identifiable and can be presented in a controlled fash-
ion, it is possible to arrange conditions to directly observe the anxious response in vivo. A Behavioral
Avoidance Test (BAT) [134] is a highly structured method of assessing avoidant behavior associated
with the feared stimulus. Generally, this procedure involves progressively exposing the individual to
the feared stimulus along some dimension (e.g., distance, time) and recording the point at which the
avoidant response is displayed. BATs can be highly individualized based on the specific stimuli that
elicit fear in the person being observed. In addition to the benefit of observing the anxiety responses
directly and in a controlled manner, one can use the same method of stimulus presentation during
graduated exposure treatment (see below). Although the BAT has been a widely utilized observational
measure for assessing certain anxiety disorders across populations, it may be especially important to
include a BAT in the assessment of anxiety disorders in individuals with ASD given that self-report
and interview data may be limited. Many of the available clinical case studies that report on the
assessment and treatment of anxiety in this population describe the use of a BAT [135, 136].
Physiological Measures
The use of psychophysiological measurement for the assessment of anxiety is commonly recom-
mended by researchers [101, 137] but rarely used. Although only a couple of studies [138, 139] have
included physiological measures for assessing anxiety in individuals with ASD, these studies demon-
strate the potential feasibility of this method. Both of these studies utilized store-bought heart rate
monitors and were able to appreciate differentiated results across conditions. However, knowledge is
still limited with regard to the selection of measures, appropriate conditions under which to measure
physiological responding, and the validity of this measure [140]. Moreover, for some individuals with
ASD, physiological measurement may be even more challenging because they may have difficulty
tolerating the equipment and procedures. Despite these limitations, the potential use of physiological
measures should continue to be explored as these could provide additional information regarding the
situations that cause increased arousal in individuals with ASD, especially for those individuals who
are unable to reliably verbalize or report this information due to language deficits.
Treatment
Treating anxiety disorders in children with ASD can be a challenge given the paucity of the research
in this area, despite an extensive body of research on the treatment of anxiety in typically developing
children. As described below, there are some promising treatment options, but caution needs to be
taken when recommending these treatments until more evidence of their efficacy has been established
for children with ASD. These treatment options include (1) behavioral treatment, which is aimed at
treating specific phobia; (2) cognitive behavioral treatment (CBT) for children with HFA, which is
aimed at treating a wide range of anxiety disorders; and (3) pharmacological treatment for repetitive
and ritualistic behaviors. Unfortunately, there are not many rigorous studies on specific anxiety disor-
ders or symptoms in this population. Therefore, the treatments described are limited to the anxiety
disorders for which there is the most research, and some of our conclusions are drawn from the litera-
ture on both individuals with ID and typically developing children.
Behavioral Treatment
A recent review by Jennett and Hagopian identified behavioral treatment as an evidence-based treat-
ment for specific phobia in individuals with ID [141]. The authors identified 38 studies published over
a 35-year time period. These studies were mainly case reports, single-case experimental designs
[142], as well as some uncontrolled group studies. Among the studies were 12 well-designed single-
case experimental studies that met the American Psychological Association (APA) Divisions 12 and
16 criteria for empirically supported treatments. Participants in the reviewed studies varied widely in
their demographics, with approximately 30 % also having an ASD diagnosis and representing the full
range of impaired intellectual functioning (i.e., mild to profound). In addition, a wide variety of age
groups from childhood to adulthood were represented. A significant proportion of these studies
described the clinical nature of the problems in detail, but failed to include formal DSM diagnoses.
However, most of the clinical problems described involved avoidance of feared situations or stimuli,
such as dogs, needles, or water, and could be characterized as specific phobia. This review revealed
that behavioral treatment, involving the use of graduated exposure and reinforcement, has been
sufficiently researched to characterize this class of interventions as a “well-established” evidence-
based treatment for individuals with ID. This finding is consistent with literature on the treatment of
specific phobias in typically developing children [143]. Although there is not much research specifically
on the use of behavioral treatment for individuals with ASD, it is reasonable to believe that this inter-
vention may be efficacious for this population based on the research support in both typically devel-
oping children and individuals across the range of intellectual functioning.
The main components of behavioral treatment are graduated exposure and reinforcement. These
components are also among the main components in CBT (as described below) and, therefore, can be
applied to both low functioning individuals (i.e., IQ < 70) with ASD and those with HFA. If a child
needs help understanding or participating in the exposure, supplemental behavioral components such
as prompting, modeling, response prevention, or the use of distracting stimuli can be used in order to
facilitate it. The determination of whether these components are necessary should be based on the
needs and functioning level of the individual requiring treatment, but may be used as part of any treat-
ment package utilizing graduated exposure.
Graduated Exposure
As described in chapter “Cognitive-Behavioral Treatment for Pediatric Anxiety Disorders,” graduated

exposure is most appropriate for anxiety disorders in which there is a specific stimulus that the indi-
vidual is attempting to avoid and, therefore, is most applicable to disorders such as specific phobia,
social phobia, and OCD. With typically developing individuals, graduated exposure involves devel-
oping a fear hierarchy ranging from least to most feared stimuli based on the individual’s verbal
report. The individual is gradually exposed from lesser to more feared stimuli while maintaining
appropriate approach responses and low levels of anxiety. For individuals with ASD who may not be
able to generate a fear hierarchy based on verbal report, the hierarchy may be developed based on the
results of a BAT (as described above) or derived by the therapist based on other assessment findings.
In the latter case, the therapist may generate a range of stimulus variations by altering the feared
stimulus along a physical dimension, such as its distance from the individual, the duration of contact,
or size of the stimulus. Regardless of how the hierarchy is developed, graduated exposure involves
systematically exposing the participant to variations of the feared stimulus that progress to closer
approximations of the actual feared stimulus. Progression along the hierarchy is based on the partici-
pant successfully completing the previous step, ideally with minimal anxiety. Based on the partici-
pant’s progress, the hierarchy can be changed by including intermediate stimulus variations.
Based on the basic learning process of extinction, exposure aims to extinguish any associations
between the feared stimulus and aversive events (such as intense physiological arousal) by presenting
the feared stimulus in the absence of those aversive events. Consequently, for this approach to suc-
cessfully result in extinction, it is critical that exposure to the feared stimulus not be paired with any
aversive events (including extreme anxiety), or result in escape/avoidance from the stimulus that
could strengthen avoidance and produce counter-therapeutic effects. Ideally, the exposure session
should be arranged to minimize the likelihood that the target stimulus will be avoided by (1) gradually
progressing from lesser to more anxiety-provoking stimuli and (2) programming reinforcement for
successful approach during stimulus presentations.
For example, if a child is fearful of dogs, the hierarchy should involve exposing the child to a dog
starting at a distance that is comfortable and then progressively getting closer to the dog until the child
is within arm’s reach or is able to touch it [135, 138]. Reinforcement should be programmed for suc-
cessfully completing the steps of the hierarchy (see below for more information). If no starting dis-
tance is comfortable, the first step may involve showing the child a picture or video of a dog or having
the child observe a dog behind a gate (these variations will largely be a function of the child’s indi-
vidual ability to understand symbols or representations of feared stimuli). The progression through
the hierarchy should be based on the child’s pace so that avoidance or escape from the dog is not
reinforced and low levels of anxiety can be maintained throughout the exposure. For example, if the
child resists the next step of the hierarchy, he or she should be allowed to back up to a distance that is
more comfortable but should not be allowed to leave the situation entirely. If a particular step remains
difficult, such that the child is always resisting, an intermediate step can be programmed and/or the
reinforcement for approach behavior can be modified or increased.
Reinforcement
In addition to systematically exposing the individual to the feared situation, treatment should involve
reinforcement for approach responses. In anxiety disorders, the maintaining consequence for avoidant
behavior is typically negative reinforcement, in the form or either avoidance or escape from the feared
situation. Therefore, it is important to impose reinforcement procedures targeting approach responses
that are strong enough to counter or compete with the negative reinforcement maintaining escape or
avoidance. Although typically developing individuals may be able to identify powerful reinforcers
based on verbal report, for lower functioning individuals with ASD, a systematic preference assess-
ment (based on nonverbal choice responses) should be conducted to identify preferred items that may
potentially serve as reinforcers. Hagopian et al. provide a comprehensive review of the preference
assessment procedures for individuals with ASD and other developmental disabilities [144].
Reinforcers are typically delivered using response contingent schedules. For example, in a study
by Hagopian and colleagues, tokens were provided every 10 s during participation in each step of a
hierarchy for a blood draw for an individual with ID [126]. The tokens were then traded in at the
completion of the session for preferred items or activities that were identified via a preference assess-
ment. Tangible reinforcers, such as toys or preferred snacks, may also be used to reinforce approxima-
tions of the approach response [142].
Other Behavioral Treatment Components
Other behavioral components, based on the principles of learning, may be necessary to help the child
to cooperate with or understand the exposure. Some children, including those with lower functioning
ASD, may learn how to participate in the graduated exposure simply through learning the contin-
gency that approximations of an approach response lead to reinforcement. For other children, addi-
tional treatment components may be needed to facilitate this process.
Prompting may be included in the treatment package as way to assist the child to comply with the
steps of the exposure hierarchy and come into contact with the reinforcement contingencies in place.
This may especially be important when he or she is exhibiting intense anxiety or not approximating the
targeted approach response. Prompting involves supporting the child in performing the desired task, in
this case, approaching the feared stimulus. It may involve telling the child what to do in order to
approach the feared stimulus, showing the child how to approach the feared stimulus, or physically
helping the child to approach the feared stimulus. For example, in a study by Runyan and colleagues, a
least-to-most prompting hierarchy was used to help the participants complete the steps of the hierarchy
in order to successfully ride an escalator [145]. The prompting sequence consisted of a model (e.g.,
showing the participant how to step on the escalator), verbal prompt (e.g., telling the participant, “step
up”), physical prompt (e.g., touching elbow or holding hands to help the participant to step on the esca-
lator), and finally manually guiding the participant’s body through the step. A wide variety of prompt-
ing methods are available and routinely used with individuals with ASD [146], although the prompts
used may depend on the individual’s functioning level and ability to perform the required task.
Modeling involves arranging for the participant to observe another person (model) engaging with
or approaching the feared stimulus appropriately. Models may either be live [142] or observed via
video [128]. In a study by Love and colleagues, two young children with ASD were treated for fear
and avoidance of going outside and running water [142]. Prior to prompting each participant to engage
in an approach step of the exposure hierarchy, their mothers would model the step and verbalize their
lack of fear. Similarly, in a study by Erfanian and Miltenberger, two adults diagnosed with moderate
to profound ID were treated for fear of dogs: prior to exposure along the hierarchy, each participant
would engage in a preferred activity with the therapist at a far distance from a dog while observing
another adult interact positively with the dog [135].
Response prevention is another component that is sometimes used in conjunction with prompting
or modeling in order to ensure that the individual comes into contact with the feared stimulus.
Response prevention is typically done in order to implement extinction, which may involve prevent-
ing an escape response or prompting a behavior that is incompatible with avoidance (e.g., approach).
In either case, it typically involves not allowing the individual to leave the feared situation until the
targeted step is completed. For example, Rapp and colleagues treated an adolescent with ASD and
severe ID for self-injurious behaviors, elopement, and dropping associated with the avoidance of
swimming pools [129]. The participant was physically guided to approach and then occupy the pool.
Attempts to drop or elope were blocked by prompting the participant to sit in a rolling chair. Two
therapists physically guided her toward the pool by rolling the chair. When she reached the pool,
another therapist provided her with edible reinforcement. Although this study describes an effective
response prevention procedure, most studies published to date that describe the behavioral treatment
of anxiety in individuals with ASD do not include response prevention or escape extinction [141].
That is, in most cases, the individual is permitted to escape or avoid the situation. However, not
enough research has been conducted to determine whether this component should be routinely
included as part of a treatment package.
Finally, use of distracting stimuli is another component that may be used in conjunction with gradu-
ated exposure and reinforcement. This involves the noncontingent access to items during exposure,
ostensibly as a means of providing alternative reinforcement of responses incompatible with avoid-
ance. Luscre and Center incorporated distracting stimuli along with an exposure hierarchy, modeling,
and reinforcement for the treatment of children with autism displaying anxiety and resistance during
dental exams [147]. Each participant was provided with access to items such as music and preferred
toys with the intent to promote relaxation. The intervention was effective for all cases; however, data
on the participants’ level of relaxation were not reported (nor is it possible to determine the contribu-
tion of each treatment component). Although providing distracting stimuli during exposure is rela-
tively easy and a seemingly benign component, it is possible that free reinforcement can weaken the
effects of contingent reinforcement provided for successful approach behavior. Additional research is
needed before the routine use of distracting stimuli can be recommended.
Although there is not much research to date specifically on the use of graduated exposure and
reinforcement with individuals with ASD, the collective findings that it is a well-established treatment
for both individuals with and without cognitive limitations with specific phobia [141, 143] may be
sufficient evidence for the use of this treatment with individuals throughout the ASD population.
Behavioral treatment, as described above, can be highly individualized based the functioning level
and needs of the individual, utilizing additional treatment components when necessary.
Cognitive Behavioral Treatment
Recently, there has been an increase in research on the treatment of anxiety disorders specifically for
individuals with HFA. Lang and colleagues identified nine studies on modified CBT for anxiety in
individuals with ASD [148]. These studies include a range of experimental and nonexperimental
designs, with five studies that included a waitlist control group [149]. The majority of participants
across the reviewed studies were diagnosed with Asperger’s disorder, and few participants were
diagnosed with PDD-NOS or high functioning autism. The ages of the participants ranged from
preadolescence to postadolescence. Finally, the majority of studies included individuals with multi-
ple anxiety diagnoses, including OCD, GAD, separation anxiety disorder, panic disorder, social pho-
bia, and specific phobia. CBT has been classified as an evidence-based treatment for social phobia,
OCD, school refusal, and general anxiety symptoms for typically developing children [150, 151]
according to guidelines established by the APA Division 12. Thus, in the absence of other informa-
tion, and coupled with the promising preliminary evidence from investigations of CBT with indi-
viduals with HFA, it is reasonable to believe that this type of treatment may also be efficacious for
this population.
All of the research studies published to date on the use of CBT with individuals with ASD have
used a manualized approach based on commonly used treatments for typically developing children
with anxiety disorders that has been modified based on the characteristics of individuals with ASD
(see Table 2 for more information on each study) [20, 32, 110, 149, 152–162]. Most of the treatment
manuals describe the steps for individual CBT, including “Building Confidence” [159], “Coping Cat”
[160], and the manual developed by March and Mulle for OCD [161]. One describes the steps for a
group CBT approach (“Cool Kids”) [162]. Finally, some researchers [39, 153, 155, 158] created their
own manuals specific to their studies. As described in chapter “Cognitive-Behavioral Treatment for
Pediatric Anxiety Disorders,” manualized CBT for typically developing children usually involves
(1) affect recognition, (2) coping strategies, (3) cognitive restructuring, and (4) graduated exposure.
The adapted manuals for individuals with ASD include these components as well, but with modifications
such as increased structure during sessions, use of visual cues to teach key concepts, use of persevera-
tive interests and behavioral reward systems to increase motivation for participation, and simplified
cognitive restructuring [20, 32, 149, 152, 155, 156]. The majority of manuals have also been modified
to include more parent involvement in the treatment sessions. In addition, a few studies have investi-
gated the efficacy of CBT plus skills training that focus on areas of deficit commonly seen in individu-
als with ASD such as social skills or daily living skills [39, 149, 158].
Table 2 Cognitive behavioral treatment in children with autism spectrum disorders
Author (year) N Sample characteristics Anxiety diagnoses Type of treatment Treatment manual Control group Treatment outcomes
Chalfant 47 HFA (n = 13), AS SAD (n = 8), GAD 12-week group CBT with Adapted “Cool Kids” Waitlist control 71.4 % of treatment group
et al. [32] (n = 34); age 8–13 (n = 14), SP concurrent parent Program (Lyneham (random no longer met DSM-IV
(n = 20), SpP sessions et al. [162]) assignment) criteria for anxiety
(n = 3), PD disorder (vs. 0 % in
(n = 2) control group)
Lehmkuhl 1 HFA; age 12 OCD 10 sessions individual Adapted manual by March N/A Subject no longer endorsed
et al. [152] CBT with parent and Mulle [161] clinically significant
involvement symptoms of OCD on
Y-BOCS
Reaven et al. 33 ASD (n = 15), GAD (n = 22), SAD 12-week group CBT with Original treatment manual Waitlist control Parents of children in
[153] PDD-NOS (n = 4), (n = 6), SP concurrent parent written by authors treatment group
AS (n = 14); age (n = 5) sessions reported significant
8–14 decrease in severity of
anxiety symptoms
according to SCARED
(vs. no reported
decrease in control
group)
Reaven and 1 AS; age 7 OCD 14 sessions individual Adapted manual by March N/A 65 % decrease in
Hepburn CBT with parent and Mulle [161] parent-reported
[20] involvement (sertraline symptoms on
was initiated during CY-BOCS after
treatment) treatment
Schleismann 1 AS, age 6 SP 12 sessions individual Adapted “Coping Cat” N/A Subject no longer met
and Gillis CBT with parent manual (Kendall diagnostic criteria for
[154] involvement [160]) social phobia (based on
clinical judgment)
Sofronoff 71 AS; age 10–12 PD, OCD, SP, SAD, 6-week group CBT or Study-specific manual Waitlist control Significant decrease in
et al. [155] GAD (n’s not 6-week group CBT (random parent-reported anxiety
reported) with parent assignment) symptoms (according
involvement to SCAS-P) in both
groups, but greater
improvement with
parental involvement
363
(continued)
Table 2 (continued)
364
Author (year) N Sample characteristics Anxiety diagnoses Type of treatment Treatment manual Control group Treatment outcomes
Sze and Wood 1 HFA; age 11 SAD, GAD, OCD 16-week individual CBT Adapted “Building N/A Subject no longer met
[156] with parent Confidence” program diagnostic criteria for
involvement (Wood and McLeod SAD, GAD, or OCD
[159]) (according to
ADIS-C/P)
Sze and Wood 1 AS; age 10 GAD, SP Not reported Adapted “Building N/A Subject no longer met
[157] Confidence” program diagnostic criteria for
(Wood and McLeod GAD or SP (according
[159]) to ADIS-C/P)
White et al. 4 AS (n = 3), PDD-NOS GAD (n = 3), SP 12–13 sessions individual Manual created by authors N/A Three of the four subjects
[158] (n = 1); age 12–14 (n = 3), SpP CBT with parent “Multimodal Anxiety no longer met
(n = 2) involvement + 5 and Social Skills diagnostic criteria for
sessions group social Intervention” (MASSI; targeted anxiety
skills training White et al. [110]) disorder. Variable
improvement in social
competence based on
parent report (accord-
ing to SRS)
Wood et al. 40 AS (n = 3), ASD SP (n = 35), SAD 16-week individual CBT Adapted “Building Waitlist control 64.3 % of treatment
[149] (n = 20), PDD- (n = 24), OCD with parent Confidence” program (blinding, completers no longer
NOS (n = 17); age (n = 17), GAD involvement (Wood and McLeod random met diagnostic criteria
7–11 (n = 19) [159]) assignment) for anxiety disorders
(vs. 9.1 % of control
group)
H. Jennett et al.
Affect Recognition
Affect recognition involves identifying physiological symptoms or behaviors that occur when one is
anxious. The goal of this step is to increase self-awareness of symptoms or situations that may lead
to anxious feelings. Emotion recognition is impaired in some individuals with ASD [163–165]. In
order to decrease the communication demands and possible challenges with emotion recognition,
Reaven modified this step by presenting a written menu of possible physical symptoms and allowing
the participant to choose from among them instead of asking him to generate this information on his
own [166].
Acquisition and Use of Coping Strategies
After the individual is able to identify his or her physical symptoms of anxiety, coping strategies are
taught so that he or she has the tools to manage anxiety when confronted with a feared situation. The
most commonly used coping strategy for individuals with ASD is behavioral relaxation. Behavioral
relaxation usually involves progressive muscle relaxation and deep breathing. Some modified CBT
programs [32] devote the most time to teaching relaxation skills since it is a concrete exercise and
does not rely on the child’s communication skills. Other commonly taught coping strategies involve
the use of positive self-statements (see below) and distraction [20]. The majority of studies have
enhanced skills training with visual supports. For example, in a case study, Reaven and Hepburn’s
participant made a “toolbox” with cutout “tools” that were each labeled with a coping strategy and
could be used as a visual reminder to utilize that strategy during exposure sessions [20]. Other case
studies describe the use of social stories which outline the coping strategies that can be used when
facing a fear [20, 154].
Cognitive restructuring involves recognizing and challenging negative automatic thoughts. For indi-
viduals with ASD, this typically involves replacing negative automatic thoughts with more helpful
statements. For example, a child with social phobia may be taught to replace the negative automatic
thought “Those kids think I’m stupid because I don’t know what to say” with the statement “Everyone
has something interesting to say.” For individuals who are unable to identify automatic thoughts,
generic positive self-statements can be offered, such as “Nothing bad will happen” or “It’s no big
deal.” Chalfant et al. used worksheets with lists of helpful and unhelpful thoughts that the participants
could choose from rather than relying on their limited communication skills to generate them on their
own [32]. Sze and Wood also relied on visual materials, rather than spoken language, and included a
participant’s special interests to facilitate learning of these skills [156]. In particular, the participant
was allowed to draw her favorite cartoon characters and then wrote “icky” and “calm” thoughts into
thought bubbles. Across all studies of individuals with ASD, cognitive restructuring was significantly
simplified and typically was conceptualized as affect recognition and positive coping statements, as
described above [32, 152].
Graduated Exposure
Graduated exposure, as described in the behavior treatment section, is a main component of CBT.
Individuals with HFA can take a more active role in creating the hierarchy of anxiety-provoking
situations. Some of the original treatment manuals [160, 161] include visual cues such as “fear
thermometers” to assess the level of anxiety experienced throughout the exposure, and similar to
typically developing children, this strategy is effective in many of the HFA case studies as well
[154]. When engaging in exposure tasks, individuals are reminded to use their coping techniques
and report the levels of anxiety at different points in the exercise using these visual cues. As described
above, reinforcement is a necessary component to increase motivation and adherence to the expo-
sure exercises and in some cases involves the use of the child’s perseverative interests [153, 156].
For example, in one case [156], a points system was used to keep track of homework completion,
and the child was rewarded with access to activities and movies with which she was preoccupied.
Parent Involvement
Parent involvement generally involves (1) psychoeducation about the nature of anxiety and basic
principles of CBT, including how to facilitate appropriate extinction of avoidance behaviors and rein-
force appropriate alternative behaviors, and (2) homework assignments for which the parents com-
plete exposure exercises with their children outside of therapy sessions. In most cases, parent
involvement is woven throughout all therapy sessions [20, 39, 153, 158] in order to enhance general-
ization of the skills learned in session. Parents may be involved in the development of fear hierarchies
and coping skills training and then given coaching by the therapist to implement exposure sessions
with their children. Subsequent homework assignments are given where parents are asked to practice
systematically exposing their child to items on the fear hierarchy outside of the therapy session so that
the gains made by the child in the session are generalized to the natural setting. Studies have found
that CBT with parental involvement is an important component for individuals with ASD and leads to
more treatment gains compared to child-focused CBT [149, 155].
Skills Training
Skills training involves a focus on deficits specific to children with ASD that may impact the efficacy
of CBT. White and colleagues have hypothesized that social deficits in individuals with HFA may
contribute to the promotion of social anxiety in this population [39, 158]. Adolescents with HFA may
develop and maintain social anxiety because of their awareness of their own social difficulties. As a
result, they may avoid social situations and, therefore, have few opportunities to practice appropriate
social skills. Based on this hypothesis, a multicomponent manual-based program was developed
which targets both anxiety and social deficits as reciprocal influences on one another. This treatment
package includes individualized CBT, group social skills training, and parent education/involvement.
It contains the components described above plus the use of social skills training through the use of
modeling, feedback, and reinforcement. Social skills that may be targeted include initiating with
peers, conversational skills, flexibility, recognizing the cues of others, and handling rejection; see
Table 2 for more information on outcomes. Other researchers have preliminarily focused on other
areas of skill deficit, such as self-help skills and the presence of circumscribed interests [149].
Despite the promising results in the literature to date, there still remain several questions regarding
the use of CBT with individuals with HFA. More research needs to be conducted in order to determine
the contribution of the cognitive components of this treatment with this population. According to Lang
and colleagues, the fundamental mechanism of action in CBT involves a correction of dysfunctional
cognitions and a reliance on introspection [148]. However, most of the modifications necessary to gear
this treatment to individuals with ASD have been behavioral in nature, and many of the cognitive
components have been significantly reduced. Therefore, it is possible that behavioral components
alone, as described above, would be sufficient and potentially more efficient for treating the HFA
population. Additionally, there still remain several questions concerning for whom this treatment
works best. As described above, the majority of the participants in the collective research to date have
been diagnosed with Asperger’s disorder, with only a few having high functioning autism or PDD-
NOS. Given the differences in communication and cognitive skills across these diagnoses, it should
not be assumed the CBT would be equally effective for all individuals in the higher range of function-
ing on the autism spectrum. Finally, since participants in these studies typically have more than one
anxiety disorder or the groups of participants have different anxiety diagnoses, it is unclear as to which
anxiety disorders are being treated or for which anxiety disorders these treatments are most effective.
Research on the pharmacological treatment of anxiety in children with ASD is relatively lagging in
comparison to studies in typically developing children. To date, there are no controlled studies of
medications for separation anxiety disorder, generalized anxiety disorder, social phobia, or OCD in
children and adolescents with ASD. The current literature focuses on the treatment of anxiety symp-
toms as well as repetitive and ritualistic behaviors in children and adolescents with ASD. Relevant
adult data are also presented to illustrate developmental differences in treatment response. This sec-
tion will focus primarily on data from open-label and controlled drug trials of anxiety and repetitive
behaviors. Select case report studies are presented if these are the only data available for a particular
medication; these data however should be interpreted cautiously until data from controlled trials are
available. The effects of each medication reported in this section are limited to anxiety and repetitive
behaviors and not inclusive of the full range of benefits of the drug.
Selective Serotonin Reuptake Inhibitors
The selective serotonin reuptake inhibitors (SSRIs) are the most commonly prescribed medications
for children with ASD [167, 168]. Three lines of evidence spark enthusiasm for using SSRIs in chil-
dren with ASD. First, serotonergic abnormalities have been implicated in the pathophysiology of
ASD [169]. Second, double-blind placebo-controlled trials have demonstrated the effectiveness of
multiple SSRIs in the treatment of anxiety disorders, including OCD, in typically developing chil-
dren [170, 171]. Although not yet known, it is possible that the clinical presentation and pathophysi-
ology of anxiety disorders may be similar in children with and without ASD [85, 172]. Lastly, SSRIs
have a relatively benign side profile compared to other psychotropic medications (e.g., risperidone)
that are often prescribed in children with ASD, making them a preferable first-line agent for treat-
ment for anxiety.
The data on SSRIs in the treatment of anxiety and repetitive behavior in children and adolescents
with ASD are mixed with some studies demonstrating efficacy of select SSRIs (fluoxetine), whereas
other SSRIs (citalopram) show no effect. The doses of SSRIs used in these studies are lower than the
doses typically used to treat emotional disorders in typically developing children and adolescents. For
example, the mean dose of citalopram used in children with ASD was 16.5 mg [173] compared to the
mean dose of 25 mg used to treat depression in typically developing children and adolescents [174].
Similarly, the mean doses of fluoxetine were 9.9 mg [175] and 20 mg [176] in children and adoles-
cents with ASD and a same age typically developing sample, respectively. Developmental differences
in dosing of SSRIs as is also present in ASD, with adults tolerating higher doses and demonstrating
greater efficacy than children [173, 177].
Findings from several case report studies suggest that sertraline may improve anxiety in children
with ASD. Ozbayrak reported an improvement in anxiety and repetitive behavior with sertraline in
two children with Asperger’s disorder [178]. One child was a 6-year-old boy who was described to
have anxiety, excessive clinginess, repetitive questioning, preoccupations with death and blood, and
physical aggression. His anxiety, clingy behavior, and questioning improved with 25 mg of sertraline.
He became hyperactive on 50 mg of sertraline. The second child was a 13-year-old boy with an
impairing compulsive counting ritual that responded to 50 mg of sertraline.
Results from a case study of nine children with ASD, ages 6–12 years, found that sertraline
25–50 mg was beneficial in reducing transition-related anxiety and agitation [179]. Three children
demonstrated relapse after 3–7 months, whereas six children demonstrated continued benefits for a
few months. Sertraline was generally well tolerated with one child developing stomachaches and two
children exhibiting agitation on 75 mg of sertraline.
Another case report documented improvement in separation anxiety in a school-age girl with ASD
who received 150 mg sertraline [180]. The child had classic DSM-IV symptoms of separation anxiety
as assessed by an established structured diagnostic interview. Symptoms included fear of her sister
being harmed, wanting to sleep near her sister, and anxiety and restlessness when separated from her
sister. Her symptoms resolved with 6 months of sertraline treatment.
The largest and most rigorous SSRI study in children with ASD is a multisite, double-blind, pla-
cebo-controlled 12-week trial of citalopram (mean dose of 16.5 mg) in 149 children with ASD. Results
showed no significant difference in repetitive behaviors between the citalopram (32.9 % responders)
and placebo groups (34.2 % responders) [173]. Significantly more side effects occurred in the citalo-
pram versus control group (97.3 % versus 86.8 %). In the citalopram group, the most common side
effects were increased energy, impulsivity, diminished concentration, hyperactivity, stereotypy, diar-
rhea, and insomnia. Two children in the study had seizures, one of whom had preexisting seizures.
Studies of fluvoxamine indicate beneficial effects in adults but not children. In a double-blind con-
trolled study of adults with ASD, fluvoxamine (mean dose 276.7 mg/day) was effective in reducing
repetitive behavior, maladaptive behavior, and repetitive speech in 8 of 15 (53 %) patients on active
drug compared to a 0 % response in the placebo group [181]. Side effects in adults taking fluvoxamine
were mild and transient. In contrast, a placebo-controlled trial of fluvoxamine (25–250 mg/day, mean
dose = 106.9 mg/day) in 18 of 34 children with PDD showed benefit in only one (6 %) subject [182].
Side effects emerged in 14 out of 18 children and most commonly included insomnia, hyperactivity,
agitation, and aggression. The high rate of side effects may have overshadowed any type of treatment
response. An open-label study of fluvoxamine (1.5 mg/kg/day, mean maximum dose = 66.7 mg) in 18
children and adolescents also showed a less robust response than in adults [183]. There were no dif-
ferences between the active drug and placebo groups on the primary and secondary outcome mea-
sures. However, 8 of the 18 (44 %) children were noted to exhibit a partial or complete response based
on the intent-to-treat analysis. Half of the children exhibited agitation, akathisia, or behavioral activa-
tion; three dropped out due to severe symptoms.
Unlike the findings from the fluvoxamine studies, data on fluoxetine indicate comparable responses
in both adults and children. In a pediatric double-blind study (n = 45), low-dose fluoxetine (mean dose
9.9 mg/day) was superior to placebo in reducing repetitive behaviors [175]. Side effects were compa-
rable between the two groups. Similarly, a recent double-blind study in adults with ASD (n = 37)
showed that fluoxetine (mean dose 64.8 mg/day) significantly decreased repetitive behaviors com-
pared to placebo [184].
There is one open-label trial of escitalopram (mean dose 11.1 mg) that showed some improvement
in stereotypies, as well as irritability and hyperactivity, in 28 children with ASD. Only five children
tolerated the highest possible dose of escitalopram (20 mg) without experiencing side effects. Dose-
related side effects emerged in 18 subjects and included irritability (n = 7), hyperactivity (n = 6), or
both (n = 5) [185].
Collectively, these data indicate that the SSRIs work differently in children, adolescents, and adults
with ASD. Children with ASD benefit from lower doses of medications when compared to doses given
to typically children with anxiety disorders and to adults with ASD and anxiety or repetitive behaviors.
Moreover, children with ASD are more susceptible to side effects such as behavioral activation.
Other Medications
Several other medications have been tested in either placebo-controlled or open-label trials for the
treatment of anxiety and repetitive behaviors. First, two atypical antipsychotics, risperidone and arip-
iprazole, which are FDA approved for the treatment of irritability in ASD, both have beneficial effects
on reducing stereotypies. Findings from the Research Units of Pediatric Psychopharmacology’s mul-
tisite double-blind placebo-controlled trial of risperidone (0.5–3.5 mg/day) in 101 children and ado-
lescents with ASD showed a reduction in stereotypic behavior, among other symptoms, in the active
drug compared to placebo group [186]. Weight gain (2.7 ± 2.9 kg in 8 weeks), fatigue, and drowsiness
were more prevalent in the active drug versus placebo group. Two double-blind controlled trials of
aripiprazole (Marcus et al. [187]: n = 218, 5–15 mg/day; Owen et al. [188]: n = 98, 5–15 mg/day)
showed a significant reduction in stereotypies compared to those receiving placebo [187, 188].
Aripiprazole resulted in less weight gain than risperidone (approximately 1.3 kg over 8 weeks in
Marcus et al. [187]; 2.0 kg over 8 weeks in Owen et al. [188]).
Second, there is one open-label trial of buspirone (mean dose 29.3 mg/day) that demonstrated a
moderate to significant reduction in anxiety and irritability in 16 of 22 children with ASD [189].
Buspirone was well tolerated except by one child who exhibited oral-lingual dyskinesia, which
resolved after the drug was discontinued.
Third, clomipramine may be effective in reducing repetitive behavior. A double-blind placebo-
controlled study of 24 children and adolescents with ASD indicated that clomipramine (mean dose
152 mg/day) was moderately effective in reducing anger and compulsive behaviors compared to
either desipramine or placebo [190]. A later double-blind placebo-controlled study in adults found
that clomipramine was superior to placebo in reducing stereotypies and irritability [191]. Side effects
of clomipramine in these studies included tachycardia, fatigue, and tremor [190, 191].
Fourth, in a double-blind, placebo-controlled study of 13 individuals with ASD, Divalproex (mean
dose 822.92 mg/day) was effective in improving repetitive behaviors. Divalproex was well tolerated,
with no subjects dropping out due to adverse events [192].
Finally, atypical antidepressants have been examined in open-label trials. In an open-label retro-
spective study of 10 youth and young adults, venlafaxine (mean dose 24.4 mg/day) was beneficial in
reducing repetitive behaviors, ADHD symptoms, and social deficits [193]. Similarly, mirtazapine
(30.3 mg/day) reduced anxiety, maladaptive behaviors, and irritability in an open-label naturalistic
study in 26 youth and young adults with ASD [194].
Case Follow-Up
Case 1: Before starting treatment, a behavioral avoidance task is done with Jessica. It reveals that she
is unable to approach a live dog behind a fence from 50 feet. Using this benchmark at a starting point,
a graduated hierarchy is developed to expose Jessica to the dog by slowly and systematically fading
the distance between her and the dog 5 feet at a time. Her preferences are assessed in order to identify
potential rewards for following the steps of the hierarchy. For the first step of the hierarchy, a marker
is placed at 45 feet from the dog and moved along the steps of the hierarchy when Jessica is success-
ful. For each step, she is prompted to approach the marker and, if she is successful, she is allowed to
play with her preferred toys at that distance. After systematically working through the hierarchy,
Jessica is successfully able to touch her neighbor’s dog briefly and no longer tries to run away when
leaving for school in the morning.
Case 2: After completing the assessment, Danny begins individual therapy sessions with his mother.
An individualized, manual-based treatment plan is created that includes both child-focused and
parent-focused components. During the first few sessions, Danny is introduced to the visual stimulus
of a “fear thermometer” to express his level of fear in different situations. He is also taught coping
skills such as behavioral relaxation and “talking back to the fear monster” using social stories and
picture schedules. Concurrent with this, his mother meets with the therapist to receive psychoeduca-
tion on the nature of anxiety and phobias. Using the fear thermometer, Danny and his mother assist
the therapist with creating a hierarchy. During therapy and for homework assignments, Danny and
his mother participate in the graduated exposure sessions. Danny receives rewards for using his fear
thermometer and coping skills. By the end of therapy, Danny is able to go out with his parents without
his teddy bear and is able to briefly approach peers at school.
Summary
Review of the existing literature suggests that many of the behavioral assessment strategies tradition-
ally employed with non-ASD populations may be applicable to individuals with ASD, despite the
communication deficits and problems with emotion recognition that may make self-report limited or
entirely unavailable. Direct behavioral observation via BATs and behavioral monitoring in natural
settings may be the primary sources of information during both the assessment and treatment evalua-
tion phases. Treatment should be individualized based on the characteristics and functioning level of
the individual. Behavioral treatment procedures consisting of graduated exposure and reinforcement
can be used across the spectrum. Data on modified CBT with adolescents with HFA is promising.
Pharmacological trials focus primarily on treatment of repetitive behaviors rather than DSM-IV anxi-
ety disorders; these data show differential responses across medications and age groups. Despite
significant gaps in the literature, research conducted thus far is sufficient to guide clinicians on how
to proceed clinically with assessment and treatment of anxiety in individuals with ASD. Nevertheless,
additional research designed to examine the presence of other types of anxiety disorders, to develop
additional assessment strategies, and to further examine treatment efficacy for anxiety in individuals
with ASD is needed.
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Index
A environmental events, 347

Acute stress disorder (ASD) extinction-based therapies, 14
diagnosis, 178 fear-eliciting situations, 14
dissociative symptoms, 182 genetic markers, 347
DSM-V criteria, 178–181 grave emotional crisis, 347
pharmacological treatment, 197 indicators, 217
ADIS-C. See Anxiety Disorders Interview Schedule for OCD, 278–279
Children (ADIS-C) pediatric disorders (see Pediatric anxiety
Adolescence disorders)
amygdala activation, 30, 34 prevalence data, 350–351
anxiety, 26 PTSD, 280–281
BDNF gene, 33 repetitive and ritualistic behavior, 350
behavioral data, 31 sensitivity, 147
conditioning paradigm, 32 severity, 217
emotionality and cognitive-regulatory changes, 25 SM, 213–214
functional neuroimaging studies, 27, 33 social involvement, 216
GAD, SAD/SoPh, 25 SP, 276–278
striatal, 39 treatment (see Selective Mutism (SM))
Adolescent Panic Control Treatment with In Vivo tripartite model, 270
Exposures (APE), 151–152 Anxiety Disorders Interview Schedule for Children
Adolescents (ADIS-C), 103, 106
anxiety disorders (see Pediatric anxiety disorders) APD. See Avoidant personality disorder (APD)
drugs, adverse effect, 150 ASDs. See Autism spectrum disorders (ASDs)
GAD (see Generalized anxiety disorder (GAD)) Assessment
OCD (see Obsessive-compulsive disorder (OCD)) anxiety disorders (see Pediatric anxiety disorders)
PCT, 151 OCD
PDSS, 149 clinician-rated measures, 163
SCARED, 150 parent-and self-report measures, 163
Age of onset, 212 panic disorder
Anxiety. See also Pediatric anxiety disorders MASC, 149–150
age-related differences, 351 medical, 150
and chronic illness PDSS, 149
assessment, child, 319 SCARED, 150
biological response, 320 SCAS, 150
CHQ, 321 PTSD
direct physiological consequence, 320 symptoms, 188–191
gastrointestinal (GI) distress and cancer, 320 trauma exposure (see Trauma exposure)
IBD, 322 SAD
medical conditions, 320, 321 MASC, 134
medical diagnosis, 319 SAI, 135
cognitive-behavioral framework, 275 SCARED, 135
cognitive regulation, 12 SCAS, 135
disorders (see Pediatric anxiety disorders (PADs)) specific phobia, 117–118
DOI 10.1007/978-1-4614-6599-7, © Springer Science+Business Media New York 2013
380 Index
Asthma BI. See Behavioral inhibition (BI)

anxiety treatment, children, 324 Biomarkers, 47–48
chronic inflammatory condition, lungs, 323 Blood oxygen level-dependent (BOLD), 5, 10
episodic attacks, 323 Body-dysmorphic disorder (BDD), 159
psychoeducational asthma management plans, 324 BOLD. See Blood oxygen level-dependent (BOLD)
psychological reaction, 323 Brain Derived Neurotrophic Factor (BDNF) gene, 33
Autism spectrum disorders (ASDs) Brain function
anxiety (see Anxiety) adolescent samples, 25
assessment anxiety diagnoses and symptoms, 26–28
BAT, 358 attention orienting, 28–30
behavioral interviews, 356–357 face emotion processing, 32–34
broad spectrum, psychopathology, 355–356 fMRI, 26
developing children to individual, 356 genetic, maturational, and environmental
direct observation, behavior, 357 influences, 26
environmental factors, 354 reward processing, 35–36
fearful facial expressions, 355 social evaluation processing, 34–35
intense physiological arousal, 355 threat learning, 30–32
multimodal and multi-informant approach, 354 Bravery-Directed Integration (BDI) phase, 137
naturalistic behavioral observation and behavioral Buspirone
monitoring, 357–358 adverse effects, 299
negative emotional behaviors, 355 pharmacological effects, 299
physiological response, 354
comorbid psychiatric disorder, 346
definition, 347 C
diagnostic criteria, 347–349 CAMS. See Child Adolescent Anxiety Multimodal Study
dimensional classification system, 347 (CAMS)
etiology Carbon dioxide sensitivity, 148–149
environmental factors, 354 CBGT-A. See Cognitive-behavioral group therapy for
genetic, 353–354 adolescents (CBGT-A)
neurobiological, 352–353 CBT. See Cognitive-behavioral therapy (CBT)
neuropsychological, 352 CCC-2. See Children’s Communication Checklist
neurodevelopmental disorders, 346 (CCC-2)
psychiatric concerns, 346 CDI phase. See Child-Directed Interaction (CDI) phase
repetitive and ritualistic behavior, 350 Child Adolescent Anxiety Multimodal Study
social and communication skills, 346 (CAMS), 303
treatment, 358–369 Child and parent anxiety
Avoidant personality disorder (APD), 96 clinician rating scales, 250–251
convergent and divergent validity, 247
discriminant validity, 247–249
B measuring treatment effects, 250
BATs. See Behavioral approach tasks (BATs) rating scales, 239–243
BDD. See Body-dysmorphic disorder (BDD) RCADS, 244
BDI. See Bravery-Directed Integration (BDI) phase RCMAS, 245
Behavioral approach tasks (BATs) reliability, 246–247
modeling and participant modeling, 120 SCARED, 244
reinforced practice, 119–120 screening, 249–250
systematic desensitization, 119 STAIC, 246
Behavioral assessment, 370 Child-Directed Interaction (CDI) phase, 137
Behavioral inhibition (BI), 49–50, 215 Child Health Questionnaire (CHQ), 321
Behavioral treatment Childhood
distracting stimuli, 361–362 anxiety disorders, 31
graduated exposure, 359–361 behavioral studies, 31
modeling, 361 functional neuroimaging work, 26, 27
prompting, 361 GAD, 25
reinforcement, 360 striatum, 35
response prevention, 361 Childhood-specific phobia
Benzodiazepines OST, 121–122
adverse effects, 298–299 reinforced practice, 119–120
pharmacological effects, 298 Child maltreatment, 196
Index 381
Children tripartite model, 270

anxiety disorders (see Cognitive-behavioral Cognitive regulation, 11–12
treatments (CBTs)) Cognitive restructuring, 220
anxiety related emotional disorders, 135 Communication disorders, 214–215
“clingy”, 130 Concordance, 114–115
GAD (see Generalized anxiety disorder (GAD)) Conditioning
hypersensitivity to CO2, 148 contextual, 6–7
MASC, 134, 149–150 Pavlovian cued conditioning, 4–6
OCD (see Obsessive-compulsive disorder (OCD)) Contingency management, 219
PDSS, 149 Course, SAD
SAD, 148 anxiety disorders, 131
SAI, 135 panic disorder, 131–132
SCARED, 150
SCAS, 135, 150
school refusal and separation anxiety, 148 D
SSRI, 138 D-cycloserine (DCS), 122–123
Children’s Communication Checklist (CCC-2), 218 Demographic distribution, 212
CHQ. See Child Health Questionnaire (CHQ) Development
Chronic medical illness anxiety disorders, 47, 48
asthma, 322–324 internalizing disorders, 53
child’s developmental level, 318 pediatric anxiety disorders, 47, 49
comorbidity of anxiety and chronic illness, 319–322 social anxiety, 50, 52
cystic fibrosis, 317 social wariness, 49
FGID, 329–333 Disorder-specific questionnaires, 217–218
functional gastrointestinal disorders, 329–333 Disruptive behavior, 214
headache, 324–326 dlPFC. See Dorsolateral prefrontal cortex (dlPFC)
IBD, 326–329 Dorsolateral prefrontal cortex (dlPFC), 9, 11
illness experience, 318 Dysregulated fear
impact, development, 318–319 behavioral inhibition, 51, 52
oncology, 333–335 distress, 50
Clinical phenomenology. See Specific Phobia fearful children, 50
Cognitive-behavioral group therapy for adolescents toddlers, 50, 51
(CBGT-A), 105, 107
Cognitive-behavioral therapy (CBT)
adolescents and children, 106 E
CBGT-A, 105 Elimination disorder, 214
childhood social anxiety, 104 Emotion regulation, 11
and GAD, 84–85 Empirically-supported treatment (EST), 276
parental involvement, 106 Environmental vulnerability, 216
pediatric anxiety, 39 ERP. See Exposure and response prevention (ERP)
and SAD, 136 EST. See Empirically-supported treatment (EST)
and SASS, 106 Etiology
and SET-C, 104, 105 OCD
and SST, 104 biological, 161–162
Cognitive-behavioral treatments (CBTs) cognitive behavioral, 162
acquisition and use, coping strategies, 365 pediatric autoimmune neuropsychiatric disorders,
affect recognition, 365 Streptococcus, 162
anxiety disorders, 362 panic disorder
children, ASD, 362, 363–364 anxiety sensitivity, 147
cognitive restructuring, 271–272, 365 carbon dioxide sensitivity, 148–149
delivery format, 275 childhood separation anxiety disorder, 148
exposure tasks, 272–273 genetics, 147
graduated exposure, 365–366 SAD
parent involvement, 366 early developmental factors, 134
problem solving, 272 genetic and biological vulnerabilities, 133
psychoeducation, 270–271 parenting, 133–134
psychological disorders, 269 specific phobias
relapse prevention, 274 genetics, 116
relaxation/somatic management, 271 learning, 116
skills training, 366–367 nonassociative, 117
therapist characteristics, 274 parenting, 116
382 Index
Evidence base Fluoxetine, 152

methods and instruments, 231 FSSC-R. See Fear Survey Schedule for Children-Revised
non-OCD anxiety disorders, 302–306 (FSSC-R)
OCD, 300–302 Functional gastrointestinal disorders (FGID)
pharmacological augmentation strategies, 290 biological inflammatory markers, 331
Executive processes, 47–48 etiology, 330
Exposure and response prevention (ERP), 278 explanatory physical syndrome, 330
Exposure treatment, 219 parental psychopathology, 333
Extinction psychological treatment, 332
amygdala–prefrontal subnetworks control, 10 psychotropic medications, 331
animal models, 9 and TAPS, 332
cognitive-behavioral therapy, 10 Functional magnetic resonance imaging (fMRI), 26, 30,
conditioned stimulus (CS), 8 32, 34
hippocampus, 10
neuroimaging study, 10
pharmacological agents, 11 G
vmPFC, 9–10 GAD. See Generalized anxiety disorder (GAD)
GCBT. See Group cognitive-behavior therapy (GCBT)
Generalized anxiety disorder (GAD)
F adolescents, 25, 36
Familial/genetic vulnerability, 215–216 assessment tools, 80, 81
Family components-behavior therapy (FCBT), 136 course, 75–76
FCBT. See Family components-behavior therapy (FCBT) data revealing, 74
Fear, 114 description, 72
Fearful temperament diagnostic criteria, 72, 73
attachment relationship, 59 differential diagnosis, 76
attentional bias, threat, 55 etiology
behavioral inhibition, 49–50 cognitive factors, 78–79
biological correlates and mechanisms heritability, 78
autonomic reactivity, 53–54 model, 76, 77
cortisol, 53 parenting and parent–child relationship, 79–80
internalizing disorders, 53 vulnerability, 77
neural correlates, 54–55 insomnia, 71
conceptual and methodological issues, 48 and IUSC, 82
dysregulated fear (see Dysregulated fear) and NCS, 72, 74
genetics, 55–56 and OAD, 72
inhibited/fearful children develop anxiety, 52 prevalence
intrusive parenting, 58 age, 74–75
parenting behavior and inhibition, 59–61 clinical samples, 74
protective parenting, 58–59 community samples, 74
sensitive parenting, 56–58 gender, 75
social anxiety disorder, 47 race/ethnicity, 75
Fear models and PSWQ, 80
active coping, 12–14 psychiatric disorder, 72
anxiety disorders, 16 and RCMAS, 80
cognitive regulation, 11–12 and RSFC, 38
contextual conditioning, 6–7 sertraline, 85
cross-species research, 16 treatment
description, 3 CBT studies, 84–85
extinction (see Extinction) pharmacological studies, 83–84
neural mechanisms, 8, 9 and WIC, 83
Pavlovian cued conditioning, 4–6 Worry Scale, 82
reconsolidation, 14–16 and WSC, 82
social learning, 7–8 youth, 25
Fear Survey Schedule for Children-Revised Generalized social phobia, 93, 95, 96, 99
(FSSC-R), 117 Graduated exposure, 219
FGID. See Functional gastrointestinal disorders (FGID) Group cognitive-behavior therapy (GCBT), 136
Index 383
H N
Headache Neural connectivity, 38
antidepressant medications, 325 Neuroimaging, 26, 27, 30, 33, 35
behavioral interventions, 326 Neurotransmitters, 290–291
CBT, 325 Nonassociative model, fear acquisition, 117
neurologic medications, 325 Nondirective supportive therapy (NST), 193
Hypersensitivity. See Panic disorder (PD) Non-OCD anxiety disorders
CAMS, 303
GAD, 304
I panic disorder, 305
IBD. See Inflammatory bowel disease (IBD) PTSD, 305–306
ICBT. See Individual cognitive-behavior school refusal, 305
therapy (ICBT) selective mutism, 304–305
ID. See Intellectual disability (ID) social phobia, 304
Individual cognitive-behavior therapy (ICBT), 136 symptomatology, 302–303
Inflammatory bowel disease (IBD) Novel behavioral treatments
adolescents, 328 PCIT, 136–137
Crohn’s disease, 327 summer camp, 137
group psychoeducational interventions, 329 NST. See Nondirective supportive therapy (NST)
immunologic reaction, 327
nutritional therapy, 327
pharmacologic treatments, 329 O
pro-inflammatory cytokines, 329 OAD. See Overanxious disorder (OAD)
treatment for anxiety, children, 328 Obsessive-compulsive disorder (OCD)
Intellectual disability (ID), 347 adult disability, 158
Intensive treatment protocol, 151–152 alternative delivery formats, 279
Intercalated cell masses (ITC), 9, 10 anxiety-provoking stimuli, 278
Interviews, 217 assessment, 163
Intolerance of Uncertainty Scale for Children augmenting and alternative agents, 301–302
(IUSC), 82 characteristic obsessions and compulsions, 278
ITC. See Intercalated cell masses (ITC) chronic and disabling neuropsychiatric disorder, 158
IUSC. See Intolerance of Uncertainty Scale for Children classification, 159
(IUSC) comorbidity, 160
differential diagnosis, 160
effectiveness, 279
L and ERP, 278
Language problem etiology, 161–162
assessment, 218 excessive/ritualized cleaning, 158
familial/genetic vulnerability, 215–216 functional impairment, 279
SM population, 214–215 genetic factors, 159
neuropsychiatric syndrome, 169
primary pharmacological treatments, 300–301
M symptom profile, 158
MASC. See Multidimensional Anxiety Scale for treatment, 164–168
Children (MASC) Obsessive-compulsive-related disorders (OCRDs), 159
Maternal overprotection, 58, 60 OCD. See Obsessive-compulsive disorder (OCD)
Mental health concerns in chronically ill children OCRDs. See Obsessive-compulsive-related disorders
anxiety disorders, 319 (OCRDs)
PTSD, 334 Oncology
Middle-ear acoustic reflex (MEAR) thresholds, 212 behavioral therapy, 334
Mirtazapine management, anxiety, 334
adverse effects, 300 PAT, 335
pharmacological effects, 300 One-session treatment (OST), 121–122
Modeling and participant modeling, 120 OST. See One-session treatment (OST)
Multidimensional Anxiety Scale for Children (MASC), Overanxious disorder (OAD)
134, 149–150 epidemiological studies, 74
Multiple learning pathways, 116 and GAD, 72, 74
384 Index
P clinical cognitive neuroscience, 39, 40

PADs. See Pediatric anxiety disorders (PADs) deficit hyperactivity disorder and autism, 23
Panic control treatment (PCT), 151 dimensional severity ratings, 259
Panic disorder (PD) evidence-based methods, 231
agoraphobia, 144 fearful temperament (see Fearful temperament)
assessment functional connectivity
MASC, 149–150 RSFC, 37–39
medical, 150 TDFC, 36–37
PDSS, 149 GAD, SoPh and SAD, 24
SCARED, 150 global psychopathology scales, 251–254
SCAS, 150 interview schedules, 258–259
children (see Children) multi-method and multisource assessment, 232–233
comorbidity, 146 objective measures, 256–258
course, 146 physiological assessment, 259
differential diagnosis, 145 preschool assessment, 254–256
disorder description, 144–145 psychological processes, 40
etiology rating scales (see Child and parent anxiety)
anxiety sensitivity, 147 semi-structured and structured diagnostic interview
carbon dioxide sensitivity, 148–149 schedules, 233–239
childhood separation anxiety disorder, 148 striatal, 39
genetics, 147 vlPFC, 39
prevalence, 145–146 Pediatric Anxiety Rating Scale (PARS), 250
and SAD, 131–132 Pediatric GAD. See Generalized anxiety disorder (GAD)
and SSRIs, 152 Pediatric SP. See Social phobia (SP)
treatment Penn State Worry Questionnaire for children (PSWQ-C),
CBT, 151 80, 82
novel behavioral treatments, 151–152 Performance anxiety, 93, 105–106
pharmacological, 152 Pervasive developmental disorders (PDDs), 96, 347
Panic Disorder Severity Scale (PDSS), 149 Pharmacokinetics
Parent–child interaction therapy (PCIT), 136–137 drug metabolism, 291
Parent-Directed Interaction (PDI) phase, 137 drugs concentration, 291
Parenting, 116 fluoxetine, 292
Parent training, 220 inhibitors and inducers, 292
PARS. See Pediatric Anxiety Rating Scale (PARS) P450 enzymes, 291
Participant modeling, 120 Pharmacological treatment
PAT. See Psychosocial assessment tool (PAT) aripiprazole, 369
PCIT. See Parent–child interaction therapy (PCIT) atypical antidepressants, 369
PCT. See Panic control treatment (PCT) buspirone, 369
PD. See Panic disorder (PD) clomipramine, 369
PDDs. See Pervasive developmental disorders (PDDs) divalproex, 369
PDSS. See Panic Disorder Severity Scale (PDSS) placebo-controlled/open-label trials, 369
PE. See Prolonged exposure (PE) SSRIs, 367–368
Peabody Picture Vocabulary Test (PPVT-IV), 218 Phenomenology, 159
Pediatric Phobia acquisition, 116
anxiety clinical trials, 256 Post-traumatic stress disorder (PTSD)
anxiety disorders (see Pediatric anxiety disorders alternative delivery formats, 280–281
(PADs)) and ASD, 178–181
OCD (see Obsessive-compulsive disorder (OCD)) assessment (see Assessment)
PTSD (see Post-traumatic stress disorder (PTSD)) avoidance symptoms, 181–182
Pediatric anxiety disorders (PADs). See also benign hyperarousal items, 188
Psychopharmacology, PAD caregiver report forms, 190
assessment approaches., 232 effectiveness, 281
behavioral and neural responses, 24 etiology and prognosis
brain genetic risk, 186
adolescence, 25 neurobiological correlates, 186–187
amygdala, 25 posttrauma factors, 185
fear processing, 24–25 trauma characteristics, 185
function (see Brain function) exposure-based CBT, 280
categorical perspective, assessment, 233 hyperarousal symptoms, 182
CBT, 39 imaginal exposures, 273
Index 385
prevalence, 182–183 SASS. See Skills for Academic and Social Success
proposed DSM-V criteria, preschool children, 182 (SASS)
psychiatric comorbidity and differential diagnosis, SCARED. See Screen for Child Anxiety Related
183–184 Emotional Disorders (SCARED)
psychometrically sound measures, 191 SCAS. See Spence Children’s Anxiety Scale (SCAS)
reexperiencing symptoms, 178, 181 School Speech Questionnaire (SSQ), 217
symptomatology, children, 188 Screen for Child Anxiety Related Emotional Disorders
treatment (see Treatment) (SCARED)
PPVT-IV. See Peabody Picture Vocabulary Test convergent and divergent validity, parent, 253
(PPVT-IV) internal consistency and retest reliability, 253
Prolonged exposure (PE), 193–194 pediatric anxiety clinical trials, 250
PSWQ-C. See Penn State Worry Questionnaire for Selective mutism (SM)
children (PSWQ-C) assessment
Psychopharmacology, PAD disorder-specific questionnaires, 217–218
benzodiazepines, 298–299 interviews, 217
buspirone, 299 observational methods, 216–217
discontinuation, medication, 309 speech-language assessment, 218
dosing, 308 comorbidity
evidence base (see Evidence base) anxiety, 213–214
initiating medication, 307–308 communication disorders, 214–215
maintenance treatment, 309 disruptive behavior, 214
mirtazapine, 300 elimination disorder, 214
neurotransmitters, 290–291 disorder description
partial/nonresponse, 308–309 impairment, 211
pharmacokinetics, 291–292 physiological findings, 211–212
pharmacological treatments, 300 social skills deficits, 211
PTSD, 290 speech problem, 210
SNRIs, 295–296 speech variability, 211
SSRIs (see Selective serotonin reuptake inhibitors etiology
(SSRIs)) behavioral inhibition, 215
TCAs, 296–298 environmental vulnerability, 216
Psychosocial assessment tool (PAT), 335 familial/genetic vulnerability, 215–216
Psychotropic medication in medical illness, 331 prevalence and course
PTSD. See Post-traumatic stress disorder (PTSD) age of onset, 212
demographic distribution, 212
treatment
R comparative studies, 223
Randomized Clinical Trials (RCTs), 276 pharmacologic, 221–223
RCADS. See Revised Child Anxiety and Depression psychosocial, 218–221
Scale (RCADS) Selective Mutism Questionnaire (SMQ), 217
RCMAS. See Revised Children’s Manifest Anxiety Scale Selective serotonin reuptake inhibitors (SSRIs)
(RCMAS) adverse effects, 293–295
Receiver operating characteristic (ROC) analyses, 249, 250 Asperger’s disorder, 367
Reinforced practice, 119–120 pharmacological effects, 292–293
Resting state functional connectivity (RSFC), 37–39 serotonergic abnormalities, 367
Revised Child Anxiety and Depression Scale (RCADS) sertraline treatment, 368
anxiety rating scales, 247 SM patients treatment, 222, 223
cutoff scores, 250 Self-modeling, 220
Revised Children’s Manifest Anxiety Scale (RCMAS) Separation anxiety disorder (SAD)
anxiety rating scales, 249 assessment, 134–135
assessment and treatment evaluation research, 245 childhood, 148
clinical trials, 250 comorbidity, 132
performance anxiety, 245 course, 131–132
treatment evaluation, 250 disorder description, 130–131
RSFC. See Resting state functional connectivity (RSFC) etiology, 133–134
and panic disorder, 131–132
prevalence, 131
S school refusal behavior, 132
SAD. See Separation anxiety disorder (SAD) treatment, 135–138
SAI. See Separation Anxiety Inventory (SAI) Separation Anxiety Inventory (SAI), 135
386 Index
Serotonin norepinephrine reuptake inhibitors (SNRIs) etiology

adverse effects, 296 genetics, 116
broader spectrum, receptor activity, 295 learning, 116
pharmacological effects, 295–296 nonassociative, 117
SET-C. See Social Effectiveness Therapy for Children parenting, 116
(SET-C) Lang’s tripartite model, 114
Shyness, 91, 94, 95, 106 prevalence and course, 115
Skills for Academic and Social Success (SASS), 106 SSRIs, 122
SM. See Selective mutism (SM) treatment
SMQ. See Selective Mutism Questionnaire (SMQ) behavioral techniques, 119–120
SNRIs. See Serotonin norepinephrine reuptake inhibitors OST, 121–122
(SNRIs) pharmacological treatments, 122–123
Social anxiety. See Social phobia (SP) Speech
Social Effectiveness Therapy for Children (SET-C), inabilities, 210
104, 105, 107, 220–221 language assessment, 218
Social phobia (SP) variability, 211
and ADIS-C, 103 Spence Children’s Anxiety Scale (SCAS), 135, 150
adolescent psychiatric disorders, 108 Spider fear score (SPQ-C), 117
alternative delivery formats, 277–278 Spider phobia questionnaire for children, 117
and APD, 96 SSQ. See School Speech Questionnaire (SSQ)
assessment tools, 101 SSRIs. See Selective serotonin reuptake inhibitors
and BATs, 103 (SSRIs)
behavioral withdrawal and mood symptoms, 97 SST. See Social skills training (SST)
and CBT, 104–106 STAIC. See State-Trait Anxiety Inventory for Children
childhood anxiety disorders, 104 (STAIC)
comorbidity, 94–95 State-Trait Anxiety Inventory for Children (STAIC)
course, 94 chronic and acute symptoms, 246
depressive disorder, 97 clinical symptoms, 246
DSM-5, 93 discriminant validity, 248
dysthymia, 107 parent rating scales, 247
effects, comorbidity, 276–277 Systematic desensitization, 119
etiology
biopsychosocial model, 101, 102
cognitive-behavioral model, 100–101 T
environment/parenting, 99–100 TAPS. See Treatment for anxiety and physical symptoms
genetics, 97 (TAPS)
neurobiology, 98–99 Task-dependent functional connectivity (TDFC), 36–37
peer victimization, 100 TCAs. See Tricyclic antidepressants (TCAs)
temperament, 97–98 TDFC. See Task-dependent functional connectivity
fear and avoidance, 96 (TDFC)
generalized vs. non-generalized subtypes, 92 TF-CBT. See Trauma-focused cognitive behavioral
mental health, 95 therapy (TF-CBT)
panic disorder, agoraphobia, 96 Trauma exposure
PDD/ASD, 96–97 active avoidance symptoms, 187
pharmacotherapy, 106–107 children, 188, 189
physiological symptoms, anxiety, 92 child welfare system, 187
prevalence, 93 comprehensive self-report instruments, 188
rating scales, 102–103 psychiatric diagnoses, 187–188
RCTs, 276 Trauma-focused cognitive behavioral therapy (TF-CBT)
separation anxiety disorder, 96 clinical training, 191
“shyness”, 91 community-based mental health systems, 193
“social anxiety”, 92 functional behavioral analysis, 192
and SSRI, 107 measures, symptoms, 191
Social skills deficits, 211 and NST, 193
Social skills training (SST), 104, 106 Trauma-focused therapy, 186, 196
SP. See Social phobia (SP) Treatment
Specific phobia ASD
assessment, 117–118 behavioral, 359–361
comorbidity, 115 repetitive and ritualistic behavior
disorder description, 114–115 (see Pharmacological treatment)
Index 387
CBTs (see Cognitive-behavioral treatments (CBTs)) behavioral techniques, 119–120

OCD OST, 121–122
cognitive behavioral therapy, 166–168 pharmacological treatments, 122–123
novel treatments, 168 Treatment for anxiety and physical symptoms
pediatric autoimmune neuropsychiatric disorders, (TAPS), 332
Streptococcus, 168 Tricyclic antidepressants (TCAs)
pharmacotherapy, 164–165 adverse effects, 298
panic disorder indications, dosing and metabolism, 296, 297
CBT, 151 pharmacological effects, 296
novel behavioral treatments, 151–152
pharmacological, 152
pharmacologic V
fluoxetine, 222 Ventilatory physiology, 132
paroxetine, 222–223 Ventrolateral prefrontal cortex (vlPFC), 11, 29, 30
phenelzine, 223 Ventromedial prefrontal cortex (vmPFC)
sertraline, 222 amygdala neurocircuitry, 11
psychosocial and BOLD, 10
cognitive restructuring, 220 and dlPFC, 12
contingency management, 219 extinction memory, 9
graduated exposure, shaping, and stimulus hippocampus, 10
fading, 219 stressor-evoked behavior, 13
innovative psychosocial strategies, 220–221 vlPFC. See Ventrolateral prefrontal cortex (vlPFC)
parent training, 220 vmPFC. See Ventromedial prefrontal cortex (vmPFC)
relaxation training and systematic
desensitization, 220
self-modeling, 220 W
PTSD Why Worry Questionnaire (WWQ), 82
group therapy, 194 WIC. See Worry Interview for Children (WIC)
integrative approaches, 195–196 Worry
PE, 193–194 child and adolescent, 80
preventative approaches, 195 “excessive” criterion, 72
psychopharmacological intervention, 197–198 GAD, 75
relationship-based therapy, 194 metacognitive models, 78
TF-CBT (see Trauma-focused cognitive WIC, 83
behavioral therapy (TF-CBT)) WSC, 82
SAD WWQ, 82
CBT, 136 Worry Interview for Children (WIC), 83
novel behavioral treatments, 136–137 Worry Scale for Children (WSC), 82
psychopharmacological treatment, 137 WSC. See Worry Scale for Children (WSC)
specific phobia WWQ. See Why Worry Questionnaire (WWQ)

Anxiety Disorder

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Anxiety Disorder

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Current Clinical Psychiatry

Series Editor: Jerrold F. Rosenbaum

For further volumes:

Pediatric Anxiety Disorders

ISBN 978-1-4614-6598-0 ISBN 978-1-4614-6599-7 (eBook)

Library of Congress Control Number: 2013935498

© Springer Science+Business Media New York 2013

Printed on acid-free paper

Humana Press is a brand of Springer

Baltimore, MD, USA Roma A. Vasa

Part I Neurobiology and Temperament

Fear Models in Animals and Humans ....................................................................................... 3

Part II Anxiety Disorders

Generalized Anxiety Disorder in Children and Adolescents ................................................... 71

Part III Assessment and Treatment

Assessment of Anxiety Disorders: Categorical and Dimensional Perspectives ..................... 231

Part IV Special Topics

Anxiety in Children with Chronic Medical Illness .................................................................. 317

Index ............................................................................................................................................. 379

Nicholas W. Affrunti Department of Psychological and Brain Sciences, University of Louisville,

Catherine A. Hartley and Elizabeth A. Phelps

Keywords Fear • Conditioning • Extinction • Emotion regulation • Anxiety

Pavlovian Cued Conditioning

Social Learning of Fear

a Fear Extinction b Cognitive Regulation

Sensory Input Fear Expression Sensory Input Fear Expression

c Active Coping d Reconsolidation

Sensory Input Fear Expression Sensory Input Fear Expression

Amanda E. Guyer, Carrie L. Masten, and Daniel S. Pine

Keywords Anxiety • Adolescence • Childhood • Neuroimaging • Brain structure • Brain function

A.E. Guyer (*)

Brain Regions Implicated in Fear Processing

Facets of Brain Development Relevant to Pediatric Anxiety

Adolescence is a period of heightened emotionality and cognitive-regulatory changes driven in part

Brain Function in Pediatric Anxiety

Ventromedial Attention Orienting

Circuit Social Phobia

Maturational and environmental influences

Social–Emotional Information Processing

Face Emotion Processing

Social Evaluation Processing

Functional Connectivity in Pediatric Anxiety

Task-Dependent Functional Connectivity

Resting State Functional Connectivity

Treatment of Pediatric Anxiety: Implications for the Brain

role of anxiety in the reward-related pathophysiology of adolescent depression, which underscores

Conclusions and Future Directions

Kristin A. Buss and Elizabeth J. Kiel

Keywords Fearful temperament • Behavioral inhibition • Dysregulated fear • Maternal overprotection

K.A. Buss (*)

Overview of the Fearful Temperament Literature

Fear Levels as a Function of Threat

Proportion of Fear Behavior Observed

How Does Fearful Temperament Become a Disorder?

Biological Correlates and Mechanisms

Attentional Bias to Threat

Fig. 2 A conceptual graph of

Influences on Parenting Behaviors

Golda S. Ginsburg and Nicholas W. Affrunti