Nonhuman and human studies have documented the adverse effects of early life stress (ELS) on emot... more Nonhuman and human studies have documented the adverse effects of early life stress (ELS) on emotion regulation and underlying neural circuitry. Less is known about how these experiences shape social processes and neural circuitry. In this study, we thus investigated how ELS affects children's perception of, and neural response to, negative social experiences in a social exclusion paradigm (Cyberball). Twenty-five foster or adopted children with ELS (age 10.6 ± 1.8 years, 13 male and 12 female) and 26 matched nonseparated controls (age 10.38 ± 1.7 years, 12 male and 14 female) took part in a Cyberball paradigm during functional magnetic resonance imaging (fMRI). During peer rejection, children with ELS reported significantly more feelings of exclusion and frustration than nonseparated controls. On the neural level, children with ELS showed reduced activation in the dorsal anterior cingulate cortex (dACC) and dorsolateral prefrontal cortex (dlPFC), and reduced connectivity between dlPFC-dACC, areas previously implicated in affect regulation. Conversely, children with ELS showed increased neural activation in brain regions involved in memory, arousal, and threat-related processing (middle temporal gyrus, thalamus, ventral tegmental area) relative to controls during social exclusion. The number of separation experiences before entering the permanent family predicted reductions in fronto-cingulate recruitment. The relationship between early separations and self-reported exclusion was mediated by dlPFC activity. The findings suggest that ELS leads to alterations in neural circuitry implicated in the regulation of socioemotional processes. This neural signature may underlie foster children's differential reactivity to rejection in everyday life and could increase risk for developing affective disorders.
Attention-deficit/hyperactivity disorder (ADHD) is the most common behavioral disorder in childho... more Attention-deficit/hyperactivity disorder (ADHD) is the most common behavioral disorder in childhood with substantial heritability. Pharmacological and molecular genetic studies as well as characterization of animal models have implicated serotonergic dysfunction in the pathophysiology of ADHD. Here, we investigated the effect of polymorphic variants in the gene of the tryptophan hydroxylase-2 (TPH2), the rate-limiting enzyme of serotonin (5-HT) synthesis in the
BACKGROUND: The developmental course of children with conduct disorder (CD) is heterogeneous. Esp... more BACKGROUND: The developmental course of children with conduct disorder (CD) is heterogeneous. Especially children who exhibit symptoms early in their lifetimes are characterized by a negative outcome. Neurobiological aspects of CD have been investigated in these children but little is known about structural and functional brain aberrations. METHODS: We describe the developmental taxonomy of children with CD and focus on those with the early onset subtype. Structural MRI data of these children and antisocial adults are recapitulated. The impact of investigating neurobiological underpinnings of antisocial behavior and how this might contribute to future forensic and psychiatric assessments is discussed. RESULTS/ CONCLUSION: Children display similar structural aberrations of fronto-limbic structures to adults with antisocial behavior, and amygdala dysfunction might be closely related to dysregulated emotions. Though the investigation of biological factors in antisocial subjects has mad...
Journal of the American Academy of Child and Adolescent Psychiatry
Children with the early-onset type of conduct disorder (CD) are at high risk for developing an an... more Children with the early-onset type of conduct disorder (CD) are at high risk for developing an antisocial personality disorder. Although there have been several neuroimaging studies on morphometric differences in adults with antisocial personality disorder, little is known about structural brain aberrations in boys with CD. Magnetic resonance imaging and voxel-based morphometry were used to assess abnormalities in gray matter volumes in 23 boys ages 12 to 17 years with CD (17 comorbid for attention-deficit/hyperactivity disorder) in comparison with age- and IQ-matched controls. Compared with healthy controls, mean gray matter volume was 6% smaller in the clinical group. Compared with controls, reduced gray matter volumes were found in the left orbitofrontal region and bilaterally in the temporal lobes, including the amygdala and hippocampus on the left side in the CD group. Regression analyses in the clinical group indicated an inverse association of hyperactive/impulsive symptoms a...
The International Journal of Neuropsychopharmacology
Deficiencies in serotonergic (5-HT) neurotransmission have frequently been linked to altered atte... more Deficiencies in serotonergic (5-HT) neurotransmission have frequently been linked to altered attention and memory processes. With attention deficit hyperactivity disorder (ADHD) being associated with impaired attention and working memory, this study investigated the effects of a diminished 5-HT turnover achieved by rapid tryptophan depletion (RTD) on attentional performance in children and adolescents with ADHD. Twenty-two male patients with ADHD (aged 9-15 yr) received the RTD procedure Moja-De and a tryptophan (Trp)-balanced placebo (Pla) in a randomized, double-blind, within-subject crossover design on two separate study days. Lapses of attention (LA) and phasic alertness (PA) were assessed within the test battery for attentional performance under depleted and sham-depleted conditions 120 (T1), 220 (T2) and 300 (T3) min after intake of RTD/Pla. At T1 there was a significant main effect for RTD, indicating more LA under intake of a Trp-balanced Pla compared to diminished 5-HT neur...
Zeitschrift für Kinder- und Jugendpsychiatrie und Psychotherapie, 2014
Psychiatric disorders in childhood and adolescence, in particular attention deficit disorder or s... more Psychiatric disorders in childhood and adolescence, in particular attention deficit disorder or specific learning disorders like developmental dyslexia and developmental dyscalculia, affect academic performance and learning at school. Recent advances in neuroscientific research have incited an intensive debate both in the general public and in the field of educational and instructional science as well as to whether and to what extent these new findings in the field of neuroscience might be of importance for school-related learning and instruction. In this review, we first summarize neuroscientific findings related to the development of attention, working memory and executive functions in typically developing children and then evaluate their relevance for school-related learning. We present an overview of neuroimaging studies of specific learning disabilities such as developmental dyslexia and developmental dyscalculia, and critically discuss their practical implications for educatio...
Zeitschrift für Kinder- und Jugendpsychiatrie und Psychotherapie, 2008
Anorexia nervosa and Bulimia nervosa are common chronic psychiatric diseases afflicting in partic... more Anorexia nervosa and Bulimia nervosa are common chronic psychiatric diseases afflicting in particular female adolescents. During the acute phase of starvation a number of hormonal, neuropsychological and cerebral morphological changes occur. Some of these abnormalities are only partly reversible. Psychiatric comorbidities complicate the clinical picture and aggravate appropriate therapeutic interventions. The following review describes in detail the neuropsychological impairments in eating disorders, potential factors influencing cognitive performance, and resulting implications for clinical every day life.
Despite growing evidence for an association between overweight and attention-deficit/hyperactivit... more Despite growing evidence for an association between overweight and attention-deficit/hyperactivity disorder (ADHD), still little is known about the mechanisms underlying this relationship. Within a two (no ADHD, ADHD) × two (normal weight, overweight) factorial design (n = 94) we tested disordered eating behaviour in a laboratory breakfast procedure as well as delay aversion (DA) in male children aged 7-15 years. While children with ADHD tended to eat above the normal level particularly at the beginning of the meal, children with overweight tended to eat above the normal level throughout the whole meal. Furthermore, preference for immediately available food was predicted by parental ratings of inattention and neuropsychological measures of DA in overweight children, and by impulsivity in children with ADHD. Our results suggest distinct neuropsychopathological pathways to abnormal eating in ADHD and overweight. Thus, children with overweight might benefit more from specialized treatment programmes that aim at improving attention functions while in children with ADHD the treatment should focus on impulsivity.
Attentional dysfunction in children after corrective cardiac surgery in infancy has rarely been e... more Attentional dysfunction in children after corrective cardiac surgery in infancy has rarely been evaluated and is the topic of the present work. Forty unselected children, 20 with tetralogy of Fallot and hypoxemia and 20 with ventricular septal defect and cardiac insufficiency, operated on at a mean age 0.7 (SD 0.3) years with deep hypothermic circulatory arrest and low flow cardiopulmonary bypass, were evaluated at mean age 7.4 (SD 1.6) years by the computerized form of the Attention Network Test providing performance measures of three networks of attention: alerting, orienting, and executive control. Parental ratings of attentional dysfunction were derived from the Child Behavior Checklist. Results were compared with healthy controls, between patient groups, and correlated with perioperative risk factors and current neurodevelopmental status. Executive control was reduced in the tetralogy of Fallot group, alerting and orienting were found normal and not different between patient groups. Durations of aortic cross clamping inversely correlated with orienting; durations of cardiopulmonary bypass correlated with mean reaction time and inversely correlated with executive control. Motor function and acquired abilities correlated with executive control and orienting. Parent-reported problems on the Child Behavior Checklist inversely correlated with executive control and mean accuracy. Children with preoperative hypoxemia in infancy due to cyanotic cardiac defects are at increased risk for attentional dysfunction in the field of executive control, compared with normal children and with those who have acyanotic heart defects. Besides unfavorable perioperative influences, preoperative hypoxemia is considered responsible for additional damage to the highly oxygen sensitive regions of the prefrontal cortex and striate body assumed to be associated with the executive control network of attention.
Although attention deficit hyperactivity disorders (ADHD) and autism spectrum disorders (ASD) sha... more Although attention deficit hyperactivity disorders (ADHD) and autism spectrum disorders (ASD) share certain neurocognitive characteristics, it has been hypothesized to differentiate the two disorders based on their brain's reward responsiveness to either social or monetary reward. Thus, the present fMRI study investigated neural activation in response to both reward types in age and IQ-matched boys with ADHD versus ASD relative to typically controls (TDC). A significant group by reward type interaction effect emerged in the ventral striatum with greater activation to monetary versus social reward only in TDC, whereas subjects with ADHD responded equally strong to both reward types, and subjects with ASD showed low striatal reactivity across both reward conditions. Moreover, disorder-specific neural abnormalities were revealed, including medial prefrontal hyperactivation in response to social reward in ADHD versus ventral striatal hypoactivation in response to monetary reward in ...
This study reports the outcomes of childhood and adolescent eating-disordered behaviour on the de... more This study reports the outcomes of childhood and adolescent eating-disordered behaviour on the development of body mass index (BMI) and psychological functioning in young adulthood in a population-based sample in Germany (the BELLA study). Information at baseline and follow-up was obtained through a telephone interview and mailed self-report questionnaires. At both measurement points, BMI, eating disorder symptoms (SCOFF questionnaire), and symptoms of depression and anxiety were assessed in the same cohort of 771 participants (n = 420 females, n = 351 males). The age range at baseline was 11-17 years, and the age range at follow-up was 17-23 years. High scores for eating-disordered behaviour in childhood or adolescence significantly predicted eating-disordered behaviour in young adulthood (multiplicative effect estimate: 1.31; 95 % CI: 1.2-1.42, p < 0.0001), although there was a decline in prevalence (from 19.3 to 13.8 %, p = 0.002) and severity (mean decrease in SCOFF 0.07, 95 % CI: -0.01-0.14, p = 0.06). After accounting for potentially confounding variables at baseline (SES, probands' BMI, parental BMI, depressive symptoms), participants with more eating disorder symptoms at baseline had a higher risk of developing overweight (odds ratio (OR): 1.58; 95 % CI: 1.19-2.09, p = 0.001), obesity (OR = 1.67; 95 % CI: 1.03-2.66, p = 0.03), and depressive symptoms at follow-up (additive effect estimate: 0.45; 95 %CI: 0.19-0.7, p = 0.0006). Early symptoms of depression showed a significant relationship with extreme underweight in young adulthood (OR = 1.13; 95 %CI: 1.01-1.25, p = 0.02). The high stability of eating disorder symptoms and the significant association with overweight and worse mental health in adulthood underscore the need for early detection and intervention during childhood and adolescence. Youth with depression should be monitored for the development of restrictive eating disorders.
Nonhuman and human studies have documented the adverse effects of early life stress (ELS) on emot... more Nonhuman and human studies have documented the adverse effects of early life stress (ELS) on emotion regulation and underlying neural circuitry. Less is known about how these experiences shape social processes and neural circuitry. In this study, we thus investigated how ELS affects children's perception of, and neural response to, negative social experiences in a social exclusion paradigm (Cyberball). Twenty-five foster or adopted children with ELS (age 10.6 ± 1.8 years, 13 male and 12 female) and 26 matched nonseparated controls (age 10.38 ± 1.7 years, 12 male and 14 female) took part in a Cyberball paradigm during functional magnetic resonance imaging (fMRI). During peer rejection, children with ELS reported significantly more feelings of exclusion and frustration than nonseparated controls. On the neural level, children with ELS showed reduced activation in the dorsal anterior cingulate cortex (dACC) and dorsolateral prefrontal cortex (dlPFC), and reduced connectivity between dlPFC-dACC, areas previously implicated in affect regulation. Conversely, children with ELS showed increased neural activation in brain regions involved in memory, arousal, and threat-related processing (middle temporal gyrus, thalamus, ventral tegmental area) relative to controls during social exclusion. The number of separation experiences before entering the permanent family predicted reductions in fronto-cingulate recruitment. The relationship between early separations and self-reported exclusion was mediated by dlPFC activity. The findings suggest that ELS leads to alterations in neural circuitry implicated in the regulation of socioemotional processes. This neural signature may underlie foster children's differential reactivity to rejection in everyday life and could increase risk for developing affective disorders.
Attention-deficit/hyperactivity disorder (ADHD) is the most common behavioral disorder in childho... more Attention-deficit/hyperactivity disorder (ADHD) is the most common behavioral disorder in childhood with substantial heritability. Pharmacological and molecular genetic studies as well as characterization of animal models have implicated serotonergic dysfunction in the pathophysiology of ADHD. Here, we investigated the effect of polymorphic variants in the gene of the tryptophan hydroxylase-2 (TPH2), the rate-limiting enzyme of serotonin (5-HT) synthesis in the
BACKGROUND: The developmental course of children with conduct disorder (CD) is heterogeneous. Esp... more BACKGROUND: The developmental course of children with conduct disorder (CD) is heterogeneous. Especially children who exhibit symptoms early in their lifetimes are characterized by a negative outcome. Neurobiological aspects of CD have been investigated in these children but little is known about structural and functional brain aberrations. METHODS: We describe the developmental taxonomy of children with CD and focus on those with the early onset subtype. Structural MRI data of these children and antisocial adults are recapitulated. The impact of investigating neurobiological underpinnings of antisocial behavior and how this might contribute to future forensic and psychiatric assessments is discussed. RESULTS/ CONCLUSION: Children display similar structural aberrations of fronto-limbic structures to adults with antisocial behavior, and amygdala dysfunction might be closely related to dysregulated emotions. Though the investigation of biological factors in antisocial subjects has mad...
Journal of the American Academy of Child and Adolescent Psychiatry
Children with the early-onset type of conduct disorder (CD) are at high risk for developing an an... more Children with the early-onset type of conduct disorder (CD) are at high risk for developing an antisocial personality disorder. Although there have been several neuroimaging studies on morphometric differences in adults with antisocial personality disorder, little is known about structural brain aberrations in boys with CD. Magnetic resonance imaging and voxel-based morphometry were used to assess abnormalities in gray matter volumes in 23 boys ages 12 to 17 years with CD (17 comorbid for attention-deficit/hyperactivity disorder) in comparison with age- and IQ-matched controls. Compared with healthy controls, mean gray matter volume was 6% smaller in the clinical group. Compared with controls, reduced gray matter volumes were found in the left orbitofrontal region and bilaterally in the temporal lobes, including the amygdala and hippocampus on the left side in the CD group. Regression analyses in the clinical group indicated an inverse association of hyperactive/impulsive symptoms a...
The International Journal of Neuropsychopharmacology
Deficiencies in serotonergic (5-HT) neurotransmission have frequently been linked to altered atte... more Deficiencies in serotonergic (5-HT) neurotransmission have frequently been linked to altered attention and memory processes. With attention deficit hyperactivity disorder (ADHD) being associated with impaired attention and working memory, this study investigated the effects of a diminished 5-HT turnover achieved by rapid tryptophan depletion (RTD) on attentional performance in children and adolescents with ADHD. Twenty-two male patients with ADHD (aged 9-15 yr) received the RTD procedure Moja-De and a tryptophan (Trp)-balanced placebo (Pla) in a randomized, double-blind, within-subject crossover design on two separate study days. Lapses of attention (LA) and phasic alertness (PA) were assessed within the test battery for attentional performance under depleted and sham-depleted conditions 120 (T1), 220 (T2) and 300 (T3) min after intake of RTD/Pla. At T1 there was a significant main effect for RTD, indicating more LA under intake of a Trp-balanced Pla compared to diminished 5-HT neur...
Zeitschrift für Kinder- und Jugendpsychiatrie und Psychotherapie, 2014
Psychiatric disorders in childhood and adolescence, in particular attention deficit disorder or s... more Psychiatric disorders in childhood and adolescence, in particular attention deficit disorder or specific learning disorders like developmental dyslexia and developmental dyscalculia, affect academic performance and learning at school. Recent advances in neuroscientific research have incited an intensive debate both in the general public and in the field of educational and instructional science as well as to whether and to what extent these new findings in the field of neuroscience might be of importance for school-related learning and instruction. In this review, we first summarize neuroscientific findings related to the development of attention, working memory and executive functions in typically developing children and then evaluate their relevance for school-related learning. We present an overview of neuroimaging studies of specific learning disabilities such as developmental dyslexia and developmental dyscalculia, and critically discuss their practical implications for educatio...
Zeitschrift für Kinder- und Jugendpsychiatrie und Psychotherapie, 2008
Anorexia nervosa and Bulimia nervosa are common chronic psychiatric diseases afflicting in partic... more Anorexia nervosa and Bulimia nervosa are common chronic psychiatric diseases afflicting in particular female adolescents. During the acute phase of starvation a number of hormonal, neuropsychological and cerebral morphological changes occur. Some of these abnormalities are only partly reversible. Psychiatric comorbidities complicate the clinical picture and aggravate appropriate therapeutic interventions. The following review describes in detail the neuropsychological impairments in eating disorders, potential factors influencing cognitive performance, and resulting implications for clinical every day life.
Despite growing evidence for an association between overweight and attention-deficit/hyperactivit... more Despite growing evidence for an association between overweight and attention-deficit/hyperactivity disorder (ADHD), still little is known about the mechanisms underlying this relationship. Within a two (no ADHD, ADHD) × two (normal weight, overweight) factorial design (n = 94) we tested disordered eating behaviour in a laboratory breakfast procedure as well as delay aversion (DA) in male children aged 7-15 years. While children with ADHD tended to eat above the normal level particularly at the beginning of the meal, children with overweight tended to eat above the normal level throughout the whole meal. Furthermore, preference for immediately available food was predicted by parental ratings of inattention and neuropsychological measures of DA in overweight children, and by impulsivity in children with ADHD. Our results suggest distinct neuropsychopathological pathways to abnormal eating in ADHD and overweight. Thus, children with overweight might benefit more from specialized treatment programmes that aim at improving attention functions while in children with ADHD the treatment should focus on impulsivity.
Attentional dysfunction in children after corrective cardiac surgery in infancy has rarely been e... more Attentional dysfunction in children after corrective cardiac surgery in infancy has rarely been evaluated and is the topic of the present work. Forty unselected children, 20 with tetralogy of Fallot and hypoxemia and 20 with ventricular septal defect and cardiac insufficiency, operated on at a mean age 0.7 (SD 0.3) years with deep hypothermic circulatory arrest and low flow cardiopulmonary bypass, were evaluated at mean age 7.4 (SD 1.6) years by the computerized form of the Attention Network Test providing performance measures of three networks of attention: alerting, orienting, and executive control. Parental ratings of attentional dysfunction were derived from the Child Behavior Checklist. Results were compared with healthy controls, between patient groups, and correlated with perioperative risk factors and current neurodevelopmental status. Executive control was reduced in the tetralogy of Fallot group, alerting and orienting were found normal and not different between patient groups. Durations of aortic cross clamping inversely correlated with orienting; durations of cardiopulmonary bypass correlated with mean reaction time and inversely correlated with executive control. Motor function and acquired abilities correlated with executive control and orienting. Parent-reported problems on the Child Behavior Checklist inversely correlated with executive control and mean accuracy. Children with preoperative hypoxemia in infancy due to cyanotic cardiac defects are at increased risk for attentional dysfunction in the field of executive control, compared with normal children and with those who have acyanotic heart defects. Besides unfavorable perioperative influences, preoperative hypoxemia is considered responsible for additional damage to the highly oxygen sensitive regions of the prefrontal cortex and striate body assumed to be associated with the executive control network of attention.
Although attention deficit hyperactivity disorders (ADHD) and autism spectrum disorders (ASD) sha... more Although attention deficit hyperactivity disorders (ADHD) and autism spectrum disorders (ASD) share certain neurocognitive characteristics, it has been hypothesized to differentiate the two disorders based on their brain's reward responsiveness to either social or monetary reward. Thus, the present fMRI study investigated neural activation in response to both reward types in age and IQ-matched boys with ADHD versus ASD relative to typically controls (TDC). A significant group by reward type interaction effect emerged in the ventral striatum with greater activation to monetary versus social reward only in TDC, whereas subjects with ADHD responded equally strong to both reward types, and subjects with ASD showed low striatal reactivity across both reward conditions. Moreover, disorder-specific neural abnormalities were revealed, including medial prefrontal hyperactivation in response to social reward in ADHD versus ventral striatal hypoactivation in response to monetary reward in ...
This study reports the outcomes of childhood and adolescent eating-disordered behaviour on the de... more This study reports the outcomes of childhood and adolescent eating-disordered behaviour on the development of body mass index (BMI) and psychological functioning in young adulthood in a population-based sample in Germany (the BELLA study). Information at baseline and follow-up was obtained through a telephone interview and mailed self-report questionnaires. At both measurement points, BMI, eating disorder symptoms (SCOFF questionnaire), and symptoms of depression and anxiety were assessed in the same cohort of 771 participants (n = 420 females, n = 351 males). The age range at baseline was 11-17 years, and the age range at follow-up was 17-23 years. High scores for eating-disordered behaviour in childhood or adolescence significantly predicted eating-disordered behaviour in young adulthood (multiplicative effect estimate: 1.31; 95 % CI: 1.2-1.42, p < 0.0001), although there was a decline in prevalence (from 19.3 to 13.8 %, p = 0.002) and severity (mean decrease in SCOFF 0.07, 95 % CI: -0.01-0.14, p = 0.06). After accounting for potentially confounding variables at baseline (SES, probands' BMI, parental BMI, depressive symptoms), participants with more eating disorder symptoms at baseline had a higher risk of developing overweight (odds ratio (OR): 1.58; 95 % CI: 1.19-2.09, p = 0.001), obesity (OR = 1.67; 95 % CI: 1.03-2.66, p = 0.03), and depressive symptoms at follow-up (additive effect estimate: 0.45; 95 %CI: 0.19-0.7, p = 0.0006). Early symptoms of depression showed a significant relationship with extreme underweight in young adulthood (OR = 1.13; 95 %CI: 1.01-1.25, p = 0.02). The high stability of eating disorder symptoms and the significant association with overweight and worse mental health in adulthood underscore the need for early detection and intervention during childhood and adolescence. Youth with depression should be monitored for the development of restrictive eating disorders.
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