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This article reviews the role of neuropeptide Y (NPY) in the pathophysiology of post-traumatic stress disorder (PTSD) and gastrointestinal disorders such as irritable bowel syndrome (IBS) with which PTSD is highly comorbid. NPY is low in... more
This article reviews the role of neuropeptide Y (NPY) in the pathophysiology of post-traumatic stress disorder (PTSD) and gastrointestinal disorders such as irritable bowel syndrome (IBS) with which PTSD is highly comorbid. NPY is low in the cerebrospinal fluid and plasma of male combat veterans with PTSD and correlates negatively with sympathetic nervous system (SNS) hyperreactivity, PTSD symptoms and time to recovery. NPY regulation has not yet been evaluated in women with PTSD. NPY levels in bowel tissue are low in IBS with diarrhea (IBS-D) versus IBS with constipation. The density of ghrelin containing cells of the gastric oxyntic mucosa is markedly increased in IBS-D. PTSD-related SNS hyperreactivity may interact with this substrate to increase ghrelin release, which activates receptors in the lumbosacral spinal cord and basolateral amygdala to increase colonic motility and amygdala hyperreactivity, respectively. Loss of function gene polymorphisms in adrenergic α2-autoreceptor...
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Preclinical and clinical research supports a role for neuroactive steroids in the pathophysiology of posttraumatic stress disorder (PTSD). We investigated ganaxolone (a synthetic 3β-methylated derivative of allopregnanolone, a GABAergic... more
Preclinical and clinical research supports a role for neuroactive steroids in the pathophysiology of posttraumatic stress disorder (PTSD). We investigated ganaxolone (a synthetic 3β-methylated derivative of allopregnanolone, a GABAergic neuroactive steroid) for treatment of PTSD in a proof-of-concept, multisite, double-blind, placebo-controlled trial. Veteran and non-veteran participants (n = 112) were randomized to ganaxolone or placebo at biweekly escalating doses of 200, 400, and 600 mg twice daily for 6 weeks. During an open-label 6-week extension phase, the initial ganaxolone group continued ganaxolone, while the placebo group crossed over to ganaxolone. Eighty-six and 59 participants, respectively, completed the placebo-controlled and open-label phases. A modified intent-to-treat mixed model repeated measures analysis revealed no significant differences between the effects of ganaxolone and placebo on Clinician Administered PTSD Symptom (CAPS) scores, global well-being, negati...
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Prepulse inhibition (PPI) is an automatic and preattentive process, whereby a weak stimulus attenuates responding to a sudden and intense startle stimulus. PPI is a measure of sensorimotor filtering, which is conceptualized as a mechanism... more
Prepulse inhibition (PPI) is an automatic and preattentive process, whereby a weak stimulus attenuates responding to a sudden and intense startle stimulus. PPI is a measure of sensorimotor filtering, which is conceptualized as a mechanism that facilitates processing of an initial stimulus and is protective from interruption by a later response. Impaired PPI has been found in (a) healthy women during the luteal phase of the menstrual cycle, and (b) individuals with types of psychopathology characterized by difficulty suppressing and filtering sensory, motor, or cognitive information. In the current study, 47 trauma-exposed women with or without posttraumatic stress disorder (PTSD) completed a PPI session during two different phases of the menstrual cycle: the early follicular phase, when estradiol and progesterone are both low, and the midluteal phase, when estradiol and progesterone are both high. Startle stimuli were 100 dB white noise bursts presented for 50 ms, and prepulses were...
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To investigate the relative contributions of depression and dissociation, as well as posttraumatic stress disorder (PTSD), to physical health symptoms and to examine the relationships among somatic symptoms, PTSD, depression, and... more
To investigate the relative contributions of depression and dissociation, as well as posttraumatic stress disorder (PTSD), to physical health symptoms and to examine the relationships among somatic symptoms, PTSD, depression, and dissociation in relation to childhood and adult trauma exposure. Cross-sectional data are from 132 female rape survivors with PTSD assessed before engaging in a study of trauma-focused cognitive therapy for PTSD. Measures included the Pennebaker Inventory of Limbic Languidness, Clinician Administered PTSD Scale, Beck Depression Inventory, Trauma Symptom Inventory-Dissociation Subscale, Childhood Sexual Abuse Exposure Questionnaire, and Assessing Environments-III-Physical Punishment Scale. Hierarchical regression analyses revealed that only dissociative and depression symptoms contributed significantly to physical health symptoms. Similarly, among the subsample of women with either childhood sexual or physical abuse, depression and dissociation were signific...
Research Interests: Psychology, Clinical Psychology, Sexual Abuse, Rape, Adolescent, and 15 moreMedicine, Comorbidity, Humans, Female, Young Adult, Dissociative disorders, Depressive Disorder, Physical Abuse, Beck Depression Inventory, Health Status, Psychological Trauma, Aged, Middle Aged, Adult, and Cross Sectional Studies
Current clinical practice guidelines (CPGs) for posttraumatic stress disorder (PTSD) offer contradictory recommendations regarding use of medications or psychotherapy as first-line treatment. Direct head-to-head comparisons are lacking.... more
Current clinical practice guidelines (CPGs) for posttraumatic stress disorder (PTSD) offer contradictory recommendations regarding use of medications or psychotherapy as first-line treatment. Direct head-to-head comparisons are lacking. Systemic review of Medline, EMBASE, PILOTS, Cochrane Central Register of Controlled Trials, PsycINFO, and Global Health Library was conducted without language restrictions. Randomized clinical trials ≥8 weeks in duration using structured clinical interview-based outcome measures, active-control conditions (e.g. supportive psychotherapy), and intent-to-treat analysis were selected for analyses. Independent review, data abstraction, and bias assessment were performed using standardized processes. Study outcomes were grouped around conventional follow-up time periods (3, 6, and 9 months). Combined effect sizes were computed using meta-analyses for medication versus control, medication pre-/posttreatment, psychotherapy versus control, and psychotherapy p...
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The propensity to acquire and retain conditioned fear responses may contribute to the risk of developing and maintaining posttraumatic stress disorder (PTSD) following a traumatic event. There is growing evidence that the gonadal hormones... more
The propensity to acquire and retain conditioned fear responses may contribute to the risk of developing and maintaining posttraumatic stress disorder (PTSD) following a traumatic event. There is growing evidence that the gonadal hormones estrogen and progesterone are associated with how well women retain extinction of previously conditioned fear responses. Thus, sex steroid effects may contribute to the increased prevalence of PTSD in women. For the current study, 32 nonmedicated female trauma survivors with and without PTSD completed a differential fear conditioning task both during the early follicular phase of the menstrual cycle when estradiol and progesterone levels are low, and during the midluteal phase when estradiol and progesterone levels are high. Skin conductance served as the measure of conditioned fear. Women with PTSD, compared to those without, showed impaired retention of extinction learning in the midluteal phase of the menstrual cycle. Therefore, the impact of me...
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Epidemiological research has demonstrated that tobacco use and posttraumatic stress disorder (PTSD) frequently co-occur and are highly prevalent among Veterans; research with female Veterans is limited. Given the increasing numbers of... more
Epidemiological research has demonstrated that tobacco use and posttraumatic stress disorder (PTSD) frequently co-occur and are highly prevalent among Veterans; research with female Veterans is limited. Given the increasing numbers of women deployed to combat zones in recent conflicts, the objective of the current study was to examine gender-specific associations between deployment stress, tobacco use and postdeployment PTSD symptoms. Two thousand thirteen Veterans deployed to Afghanistan and Iraq (50.9% female; mean age = 35.53) completed a postdeployment, mailed survey that assessed tobacco use before, during, and after deployment, deployment stressors, and postdeployment PTSD symptoms. Warfare stress was associated with initiation and increases in tobacco use during deployment in both men and women, whereas harassment stress was associated with initiation and increases in tobacco use in women only. Only among women was continued postdeployment tobacco use associated with postdepl...
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Preclinical and clinical studies demonstrate a hyperactivity of the norepinephrine system in patients with posttraumatic stress disorder (PTSD). a(2) adrenergic agonists have been shown to ameliorate symptoms of PTSD, likely because of... more
Preclinical and clinical studies demonstrate a hyperactivity of the norepinephrine system in patients with posttraumatic stress disorder (PTSD). a(2) adrenergic agonists have been shown to ameliorate symptoms of PTSD, likely because of their ability to dampen noradrenergic tone. This study tests the ability of the a(2) adrenergic agonist, guanfacine, to reduce the symptoms of PTSD. Patients with chronic PTSD were randomized (1:1) to an 8-week double-blind, placebo-controlled treatment of guanfacine followed by a 2 month open label extension phase. Patients were maintained on their stable doses of allowed antidepressants during the trial. Efficacy was measured by the following assessment scales: Clinician Administered PTSD Scale (CAPS), Montgomery Asberg Depression Rating Scale (MADRS), Clinical Global Impression-Severity (CGI-S), Clinical Global Impression-Improvement (CGI-I), and Davidson Trauma Scale (DTS, self-report). There were no significant differences in the drug versus plac...
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An appreciation for the potential role of anomalous neurobiologic processes in the etiology of childhood psychiatric illness did not emerge as a consistent theme of clinical research until the early 1960s. Before that time, etiologic... more
An appreciation for the potential role of anomalous neurobiologic processes in the etiology of childhood psychiatric illness did not emerge as a consistent theme of clinical research until the early 1960s. Before that time, etiologic constructs were premised on an interaction between psychodynamic factors and poorly defined constitutional factors. However, observation of the powerful effects of neuropharmacologic agents on behavior and growing knowledge of the functional neuroanatomy of neurotransmitter systems provided a strong impetus to biologically oriented research in the area of child and adolescent psychiatry. Since then, a pattern has emerged whereby clinical investigators incorporate newly identified and measurable components of the neural substrate into heuristic schemes of causation, in an attempt to advance our understanding of the pathophysiology of child psychiatric disorders.
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Research Interests: Psychiatry, Mental Health, Primary Health Care, Depression, Eating Disorders, and 15 moreMedicine, Comorbidity, Population, Humans, Female, Depressive Disorder, Boston, Aged, Prevalence, Middle Aged, Adult, Retrospective Studies, Military Women and Veterans, Psychology and Cognitive Sciences, and Medical and Health Sciences
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Research Interests: Endocrinology, Depression, Fear, Neuropsychopharmacology, Medicine, and 15 moreHippocampus, Internal Medicine, Cues, Animals, Male, Neuronal Plasticity, Neurons, Dentate Gyrus, Neurotrophic Factors, Hippocampal formation, Acoustic Stimulation, Avoidance Learning, Medical and Health Sciences, Male rat, and Electric stimulation
Individuals with post-traumatic stress disorder (PTSD) show a cognitive bias for threatening information, reflecting dysregulated executive control for affective stimuli. This study examined whether comorbid mild Traumatic Brain Injury... more
Individuals with post-traumatic stress disorder (PTSD) show a cognitive bias for threatening information, reflecting dysregulated executive control for affective stimuli. This study examined whether comorbid mild Traumatic Brain Injury (mTBI) with PTSD exacerbates this bias. A computer-administered Affective Go/No-Go task measured reaction times (RTs) and errors of omission and commission to words with a non–combat-related positive or negative valence in 72 deployed United States service members from the wars in Iraq and Afghanistan. Incidents of military-related mTBI were measured with the Boston Assessment of Traumatic Brain Injury-Lifetime. PTSD symptoms were measured with the Clinician-Administered PTSD Scale. Participants were divided into those with (mTBI+,n= 34) and without a history of military-related mTBI (mTBI−,n= 38). Valence of the target stimuli differentially impacted errors of commission and decision bias (criterion) in the mTBI+ and mTBI− groups. Specifically, withi...
Research Interests: Psychology, Traumatic Brain Injury, Cognition, Attention, Medicine, and 15 moreComorbidity, Executive Function, Military, Affect, Humans, United States, Female, Male, Veterans, Deployment, Adult, Task Performance and Analysis, Brain injuries, Psychology and Cognitive Sciences, and Medical and Health Sciences
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As smoking rates in the general population continue to fall in response to new information and changing social values, the continued high rate of smoking among persons with psychiatric disorders has caught the attention of society at many... more
As smoking rates in the general population continue to fall in response to new information and changing social values, the continued high rate of smoking among persons with psychiatric disorders has caught the attention of society at many levels: public health officials, medical and mental health care providers, and concerned family members alike. As a consequence, research studies aimed at quantifying the problem and understanding its cause have increased dramatically over the past several years. The following review first examines epidemiological studies that have revealed a bidirectional causal relationship between tobacco dependence and posttraumatic stress disorder (PTSD), one of several mental health disorders in which tobacco dependence remains prevalent and resistant to intervention. Second, we use a translational neuroscience perspective to discuss possible neurobiological mediators of the relationship between PTSD and tobacco dependence, hoping to spur further human and an...
Research Interests: Psychology, Psychiatry, Psychopharmacology, Mental Health, Medicine, and 15 moreCortisol, Humans, Clinical research, Posttraumatic stress disorder, Nicotine, Animals, Psychological Intervention, HPA axis, Fear conditioning, Mental Health Care, Epidemiologic Studies, General Population, Psychology and Cognitive Sciences, Psychiatric disorder, and Medical and Health Sciences
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Research Interests: Endocrinology, Psychology, Cognitive Science, Medicine, Gene expression, and 15 moreAggressive Behavior, Internal Medicine, Mice, Animals, Enzyme, FLUOXETINE, Neuronal Activity, Receptor, Psychotic Disorders, Enzymatic Activity, Neurosciences, Selective serotonin reuptake inhibitor, GABAA receptor, Psychiatric disorder, and mRNA expression
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There are few topics in the field of traumatic stress studies that clinicians approach more ambivalently than considerations of genetic factors associated with vulnerability or resistance to traumatization. Historically, individuals... more
There are few topics in the field of traumatic stress studies that clinicians approach more ambivalently than considerations of genetic factors associated with vulnerability or resistance to traumatization. Historically, individuals suffering from combat-related posttraumatic stress disorder (PTSD) received diagnoses including "soldier's heart" or "neurocirculatory asthenia," and were frequently viewed as possessing characteristics that cast them in a disparaging light, such as "constitutional inferiority" and "lack of virility" (Campbell, 1918; see Krystal et al., 1989). Early studies implicated race as an important factor influencing the vulnerability to psychological stress (cf. Dunn, 1942). However, these studies attempted to use flawed clinical data to support widely held societal prejudices against minority groups, similar to early misguided efforts to characterize the inheritance of intelligence (Gould, 1981 ). Similarly, German aut...
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Substance use may influence study results in human subjects research. This study aims to report the concordance between self-report and biochemical assessments of substance use and test the effect of methods to reduce false reports of... more
Substance use may influence study results in human subjects research. This study aims to report the concordance between self-report and biochemical assessments of substance use and test the effect of methods to reduce false reports of abstinence in trauma-exposed women participating in a research study. In this pilot study, substance use was assessed during telephone prescreening and via self-report and biochemical verification (i.e., urine toxicology and alcohol breathalyzer tests) at an in-person evaluation. Due to the high number of participants who tested positive for substances despite self-reporting abstinence during prescreening, study procedures were modified to disincentivize false self-reports of substance use two thirds of the way through recruitment. New potential participants were explicitly informed during prescreening and informed consent that a positive drug or alcohol test during screening would result in exclusion from the study and withholding of payment. Prior to...
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3α-5α-Tetrahydroprogesterone, a progesterone metabolite also known as allopregnanolone, and 5α-androstane-3α,17β-diol, a testosterone metabolite also known as 3α-androstanediol, are neuroactive steroids and positive GABAA receptor... more
3α-5α-Tetrahydroprogesterone, a progesterone metabolite also known as allopregnanolone, and 5α-androstane-3α,17β-diol, a testosterone metabolite also known as 3α-androstanediol, are neuroactive steroids and positive GABAA receptor allosteric modulators. Both anorexia nervosa (AN) and obesity are complicated by affective comorbidities and hypothalamic-pituitary-gonadal dysregulation. However, it is not known whether neuroactive steroid levels are abnormal at the extremes of the weight spectrum. We hypothesized that serum allopregnanolone and 3α-androstanediol levels would be decreased in AN compared with healthy controls (HC) and negatively associated with affective symptoms throughout the weight spectrum, independent of body mass index (BMI). Thirty-six women were 1 : 1 age-matched across three groups: AN, HC, and overweight/obese (OW/OB). AN were amenorrheic; HC and OW/OB were studied in the follicular phase. Fasting serum neuroactive steroids were measured by gas chromatography/ma...
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Stress analysis by FLIR (forward-looking infrared) evaluation (SAFE) has been demonstrated to monitor sweat pore activation (SPA) as a novel surrogate measure of sympathetic nervous system (SNS) activity in a normal population. SNS... more
Stress analysis by FLIR (forward-looking infrared) evaluation (SAFE) has been demonstrated to monitor sweat pore activation (SPA) as a novel surrogate measure of sympathetic nervous system (SNS) activity in a normal population. SNS responses to a series of 15 1-s, 82 dB, white noise bursts were measured by skin conductance (SC) and SAFE monitoring of SPA on the fingers (FiP) and face (FaP) in 10 participants with posttraumatic stress disorder (PTSD) and 16 trauma-exposed participants without PTSD (Mage = 48.92 ± 12.00 years; 26.9% female). Within participants, SC and FiP responses across trials were strongly correlated (r = .92, p < .001). Correlations between SC and FaP (r = .76, p = .001) and between FiP and FaP (r = .47, p = .005) were smaller. The habituation of SNS responses across the 15 trials was substantial (SC: d = -2.97; FiP: d = -2.34; FaP: d = -1.02). There was a strong correlation between habituation effects for SC and FiP (r = .76, p < .001), but not for SC and...
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Allopregnanolone and its equipotent stereoisomer, pregnanolone (together termed ALLO), are neuroactive steroids that positively and allosterically modulate the action of gamma-amino-butyric acid (GABA) at GABAA receptors. Levels of ALLO... more
Allopregnanolone and its equipotent stereoisomer, pregnanolone (together termed ALLO), are neuroactive steroids that positively and allosterically modulate the action of gamma-amino-butyric acid (GABA) at GABAA receptors. Levels of ALLO are reduced in the cerebrospinal fluid of female premenopausal patients with post-traumatic stress disorder (PTSD), a severe, neuropsychiatric condition that affects millions, yet is without a consistently effective therapy. This suggests that restoring downregulated brain ALLO levels in PTSD may be beneficial. ALLO biosynthesis is also decreased in association with the emergence of PTSD-like behaviors in socially isolated (SI) mice. Similar to PTSD patients, SI mice also exhibit changes in the frontocortical and hippocampal expression of GABAA receptor subunits, resulting in resistance to benzodiazepine-mediated sedation and anxiolysis. ALLO acts at a larger spectrum of GABAA receptor subunits than benzodiazepines, and increasing corticolimbic ALLO ...
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Chronic pain and posttraumatic stress disorder (PTSD) are disabling conditions that affect biological, psychological and social domains of functioning. Clinical research demonstrates that patients who suffer from chronic pain and PTSD in... more
Chronic pain and posttraumatic stress disorder (PTSD) are disabling conditions that affect biological, psychological and social domains of functioning. Clinical research demonstrates that patients who suffer from chronic pain and PTSD in combination experience greater pain, affective distress, and disability than patients with either condition alone. Additional research is needed to delineate the interrelated pathophysiology of chronic pain and PTSD, with the goal of facilitating more effective therapies to treat both conditions more effectively; current treatment strategies for chronic pain associated with PTSD have limited efficacy and place a heavy burden on patients, who must visit various specialists in order to manage these conditions separately. This article focuses on neurobiological factors that may contribute to the co-prevalence and synergistic interactions of chronic pain and PTSD. First we outline how circuits that mediate emotional distress and physiological threat, in...
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There are few topics in the field of traumatic stress studies that clinicians approach more ambivalently than considerations of genetic factors associated with vulnerability or resistance to traumatization. Historically, individuals... more
There are few topics in the field of traumatic stress studies that clinicians approach more ambivalently than considerations of genetic factors associated with vulnerability or resistance to traumatization. Historically, individuals suffering from combat-related posttraumatic stress disorder (PTSD) received diagnoses including “soldier’s heart” or “neurocirculatory asthenia,” and were frequently viewed as possessing characteristics that cast them in a disparaging light, such as “constitutional inferiority” and “lack of virility” (Campbell, 1918; see Krystal et al., 1989). Early studies implicated race as an important factor influencing the vulnerability to psychological stress (cf. Dunn, 1942). However, these studies attempted to use flawed clinical data to support widely held societal prejudices against minority groups, similar to early misguided efforts to characterize the inheritance of intelligence (Gould, 1981). Similarly, German authorities abused genetic arguments to justify denying the claims of Jewish survivors of the Nazi concentration camps for reparation for long-term psychiatric sequelae of their traumatization (Eisler, 1963/1964, 1967; Kestenberg, 1980). The relatively greater progress made in characterizing the environmental factors that influence subsequent stress response, such as the importance of early childhood trauma (Herman, 1992; Krystal, 1988) and the impact of parental traumatization on parent—child relationships (Danieli, 1980; Oliver, 1993; Rosenheck, 1986), further compounds concerns about overestimating genetic factors associated with PTSD.
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Post Traumatic Stress Disorder (PTSD) sometimes develops following exposure to very stressful or traumatic events such as motor vehicle accidents, rape, and war. It is arguably the signature injury of the conflicts in Iraq and... more
Post Traumatic Stress Disorder (PTSD) sometimes develops following exposure to very stressful or traumatic events such as motor vehicle accidents, rape, and war. It is arguably the signature injury of the conflicts in Iraq and Afghanistan. Previous studies have ...
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Although many people are exposed to trauma, only some individuals develop posttraumatic stress disorder; most do not. It is possible that humans differ in the degree to which stress induces neurobiological perturbations of their threat... more
Although many people are exposed to trauma, only some individuals develop posttraumatic stress disorder; most do not. It is possible that humans differ in the degree to which stress induces neurobiological perturbations of their threat response systems, which may result in a differential capacity to cope with aversive experiences. This study explored the idea that differences in the neurobiological responses of individuals exposed to threat are significantly related to psychological and behavioral indices. Individual differences in neurohormonal, psychological, and performance indices among 44 healthy subjects enrolled in US Army survival school were investigated. Subjects were examined before, during, and after exposure to uncontrollable stress. Stress-induced release of cortisol, neuropeptide Y, and norepinephrine were positively correlated; cortisol release during stress accounted for 42% of the variance in neuropeptide Y release during stress. Cortisol also accounted for 22% of the variance in psychological symptoms of dissociation and 31% of the variance in military performance during stress. Because dissociation, abnormalities in the hypothalamic-pituitary-adrenocortical axis, and catecholamine functioning have all been implicated in the development of stress disorders such as posttraumatic stress disorder, these data suggest that some biological differences may exist before index trauma exposure and before the development of stress-related illness. The data also imply a relationship among specific neurobiological factors and psychological dissociation. In addition, the data provide clues about the way in which individuals&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39; psychobiological responses to threat differ from one another.
Research Interests: Medicine, Psychosomatic Medicine, Humans, Male, Dissociative disorders, and 12 morePsychosomatic, Adult, Neuropeptide Y, Catecholamines, Psychological Stress, Cognition disorders, Severity of Illness Index, Neuropsychological Tests, Recovery of Function, Psychology and Cognitive Sciences, hydrocortisone, and Medical and Health Sciences
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To assess baseline and modulated acoustic startle responses in adolescent girls with posttraumatic stress disorder (PTSD). Twenty-eight adolescent girls with PTSD and 23 healthy control girls were recruited for participation in the study.... more
To assess baseline and modulated acoustic startle responses in adolescent girls with posttraumatic stress disorder (PTSD). Twenty-eight adolescent girls with PTSD and 23 healthy control girls were recruited for participation in the study. Acoustic stimuli were bursts of white noise of 104 dB presented biaurally through headphones. Baseline startle responses as well as prepulse inhibition, a 1,000-Hz prestimulation tone presented 120 milliseconds before the startle stimulus for 30 milliseconds, and prepulse facilitation, a 1000-Hz prestimulation tone presented continuously for 2, 000 milliseconds before the startle stimulus, were compared in these two groups of girls. At baseline and under neutral testing conditions, the magnitude of the startle response (eye blink) did not differ significantly between girls with PTSD and healthy control girls. There were no significant differences in the degree of prepulse inhibition or facilitation between the two groups of girls. Unlike combat veterans with PTSD, adolescent girls with PTSD who report exaggerated startle may not have exaggerated baseline acoustic startle responses in the laboratory. Further research should explore whether girls with PTSD demonstrate altered startle responses under stress and/or evidence of other types of psychophysiological abnormalities.
Research Interests: Psychology, Perception, Electrophysiology, Cognition, Stress, and 15 moreAdolescent, Comparative Study, Medicine, Startle Reflex, Prepulse Inhibition, Humans, Child, Posttraumatic stress disorder, Female, Facilitation, Adult, Blinking, Acoustic Stimulation, Psychology and Cognitive Sciences, and Medical and Health Sciences
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Allopregnanolone and pregnanolone—neurosteroids synthesized from progesterone in the brain, adrenal gland, ovary and testis—have been implicated in a range of neuropsychiatric conditions including seizure disorders, post-traumatic stress... more
Allopregnanolone and pregnanolone—neurosteroids synthesized from progesterone in the brain, adrenal gland, ovary and testis—have been implicated in a range of neuropsychiatric conditions including seizure disorders, post-traumatic stress disorder, major depression, post-partum depression, pre-menstrual dysphoric disorder, chronic pain, Parkinson’s disease, Alzheimer’s disease, neurotrauma, and stroke. Allopregnanolone and pregnanolone equipotently facilitate the effects of gamma-amino-butyric acid (GABA) at GABAA receptors, and when sulfated, antagonize N-methyl-D-aspartate receptors. They play myriad roles in neurophysiological homeostasis and adaptation to stress while exerting anxiolytic, antidepressant, anti-nociceptive, anticonvulsant, anti-inflammatory, sleep promoting, memory stabilizing, neuroprotective, pro-myelinating, and neurogenic effects. Given that these neurosteroids are synthesized de novo on demand, this review details the molecular steps involved in the biochemica...
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The mesoprefrontal dopamine neurons are sensitive to physical, pharmacological and psychological stressors. In this report, the role of these neurons in the response to classical fear conditioning was investigated. 6-Hydroxydopamine... more
The mesoprefrontal dopamine neurons are sensitive to physical, pharmacological and psychological stressors. In this report, the role of these neurons in the response to classical fear conditioning was investigated. 6-Hydroxydopamine lesions to the medial prefrontal cortex reduced dopamine levels to about 13% of controls but did not alter behavior during the acquisition of fear conditioning. As expected, conditioned fear increased dopamine metabolism (3,4-dihydroxyphenylacetic acid/dopamine ratio) in the nucleus accumbens in sham-lesion rats. The medial prefrontal 6-hydroxydopamine lesions did not alter this effect. During the expression, however, lesioned rats demonstrated a delayed extinction of the conditioned response without an overall increase in the initial conditioned response. This effect was consistent in rats receiving 6-hydroxydopamine lesions before or after the acquisition period. The calculated rates of extinction showed that the 6-hydroxydopamine lesioned rats had a r...
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Exposure to mild stress is known to activate dopamine (DA), serotonin (5-HT), and norepinephrine (NE) metabolism in the anteromedial prefrontal cortex (m-PFC). Neuroanatomical site(s) providing afferent control of the stress activation of... more
Exposure to mild stress is known to activate dopamine (DA), serotonin (5-HT), and norepinephrine (NE) metabolism in the anteromedial prefrontal cortex (m-PFC). Neuroanatomical site(s) providing afferent control of the stress activation of the m-PFC monoaminergic systems is at present unknown. The present study used a conditioned stress model in which rats were trained to fear a substartle-threshold tone paired previously with footshock and assessed for behavioral, neuroendocrine, and neurochemical stress responses. Bilateral NMDA-induced excitotoxic lesioning of the basolateral and central nuclei of the amygdala was performed before or after training. Pretraining amygdala lesions blocked stress-induced freezing behavior, ultrasonic vocalizations, adrenocortical activation, and dopaminergic metabolic activation in the m-PFC. Post-training amygdala lesions blocked stress-induced m-PFC DA, 5-HT, and NE metabolic activation. Post-training amygdala lesions also blocked stress-induced fre...
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Animals confronting threatening stimuli respond with a coordinated set of autonomic, neuroendocrine, neurochemical, and behavioral responses that constitute the stress response. The role of the NMDA receptor and its glycine modulatory... more
Animals confronting threatening stimuli respond with a coordinated set of autonomic, neuroendocrine, neurochemical, and behavioral responses that constitute the stress response. The role of the NMDA receptor and its glycine modulatory site was investigated in a rat conditioned stress model. Behavioral, neuroendocrine, and neurochemical analyses were conducted. Regional dopamine (DA) and serotonin (5-HT) utilization was assessed by postmortem tissue measurements of metabolite-to-parent neurotransmitter ratios. Rats were conditioned to fear a tone previously paired with footshock. The following day, rats were systemically administered saline or the NMDA glycine site antagonist (+)-HA-966 before exposure to thirty minutes of conditioned stress. Conditioned stress resulted in a selective increase in medial prefrontal cortical DA and 5-HT utilization, elevation in serum corticosterone, and freezing behavior in control animals. The conditioned stress-induced increase in DA utilization in ...
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Chapter Six Neuropsychological Underpinnings of PTSD in Children and Adolescents Helen Z. MacDonald, Iennifer I. Vasterling, and Ann ... Neuropsychological Underpinnings of PTSD 117 Although there are exceptions (Bonne et al., 2001;... more
Chapter Six Neuropsychological Underpinnings of PTSD in Children and Adolescents Helen Z. MacDonald, Iennifer I. Vasterling, and Ann ... Neuropsychological Underpinnings of PTSD 117 Although there are exceptions (Bonne et al., 2001; Gilbertson et al., 2002; Schore, 2001 ...
Serotonergic 5-HT1a agonists have recently been suggested to be effective in the treatment of human anxiety disorders. The neural mechanisms responsible for their clinical efficacy are unknown. In this study, we investigated the effects... more
Serotonergic 5-HT1a agonists have recently been suggested to be effective in the treatment of human anxiety disorders. The neural mechanisms responsible for their clinical efficacy are unknown. In this study, we investigated the effects of +/-8-hydroxy-2(di-n-propylamino)tetralin [+/-8-OH-DPAT], a serotonergic 5-HT1a agonist, on basal and stress-induced changes in dopamine utilization and release in selected forebrain dopamine terminal fields in the rat. Dopamine utilization and release were respectively assessed by neurochemical analysis of ex vivo brain tissue and by microdialysis in the freely moving animal. Systemic +/-8-OH-DPAT at doses below 225 micrograms/kg had not effect in any region except to slightly decrease dopamine utilization in the nucleus accumbens. However, at a dose of 225 micrograms/kg, +/-8-OH-DPAT significantly increased basal dopamine utilization and release in the medial prefrontal cortex, while simultaneously decreasing serotonin release in this area. By contrast, the same dose of +/-8-OH-DPAT decreased extracellular dopamine in the striatum. The effect of +/-8-OH-DPAT on the response of the dopamine system to mild footshock stress was also assessed. This 5-HT1a agonist diminished the magnitude of footshock-induced increases in prefrontal cortical dopamine utilization. These data suggest that 5-HT1a agonists may dose-dependently modulate both basal and stress-induced changes in dopamine utilization in the medial prefrontal cortex. The possible relevance of these findings to the observed clinical efficacy of 5-HT1a agonists in anxiety disorders is discussed.
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Previous studies have shown that the intravenous administration of yohimbine, an alpha 2 antagonist, increases norepinephrine turnover and has related anxiogenic effects in humans. We herein report that yohimbine also increases plasma... more
Previous studies have shown that the intravenous administration of yohimbine, an alpha 2 antagonist, increases norepinephrine turnover and has related anxiogenic effects in humans. We herein report that yohimbine also increases plasma neuropeptide Y (NPY) in healthy human subjects. This finding is consistent with previous reports in animals, but contrasts with a previously reported study in humans. NPY is a 36 amino acid peptide neurotransmitter located in sympathetic and nonsympathetic nerve fibers, as well as in brain structures such as the locus coeruleus, where it is colocalized with norepinephrine. NPY has been shown to inhibit locus coeruleus neuronal firing, decrease norepinephrine release, and increase postsynaptic noradrenergic signal transduction. When administered centrally, NPY also has anxiolytic properties. This study therefore suggests that yohimbine challenge may be useful in assessing NPY and noradrenergic system interactions in neuropsychiatric disorders such as panic disorder or post traumatic stress disorder in which noradrenergic system dysfunction has been observed.