Beate Herpertz-Dahlmann

Sex Differences and the Impact of Steroid Hormones on the Developing Human Brain

Little is known about the hormonal effects of puberty on the anatomy of the developing human brain. In a voxel-based morphometry study, sex-related differences in gray matter (GM) volume were examined in 46 subjects aged 8-15 years. Males had larger GM volumes in the left amygdala, whereas females had larger right striatal and bilateral hippocampal GM volumes than males. Sexually dimorphic areas were related to Tanner stages (TS) of pubertal development and to circulating level of steroid hormones in a subsample of 30 subjects. Regardless of sex, amygdala and hippocampal volumes varied as a function of TS and were associated with circulating testosterone (TEST) levels. By contrast, striatal GM volumes were unrelated to pubertal development and circulating steroid hormones. Whole-brain regression analyses revealed positive associations between circulating estrogen levels and parahippocampal GM volumes as well as between TEST levels and diencephalic brain structures. In addition, a negative association was found between circulating TEST and left parietal GM volumes. These data suggest that GM development in certain brain regions is associated with sexual maturation and that pubertal hormones might have organizational effects on the developing human brain.

Dysfunctional Attentional Networks in Children with Attention Deficit/Hyperactivity Disorder: Evidence from an Event-Related Functional Magnetic Resonance Imaging Study

BACKGROUND Although there is evidence for attentional dysfunction in children with attention deficit/hyperactivity disorder (ADHD), the neural basis of these deficits remains poorly understood. METHODS We used event-related functional magnetic resonance imaging (fMRI) to investigate brain activations related to three particular aspects of attention: alerting, reorienting, and executive control. Sixteen medication-naive boys with ADHD and 16 healthy boys, aged 8 to 12 years, were studied. RESULTS Behaviorally, children with ADHD showed a significant impairment only in their executive control system compared to healthy subjects. Neurally, children with ADHD (relative to controls) recruited deviant brain regions for all three attentional networks: less right-sided activation in the anterior cingulate gyrus during alerting, more fronto-striatal-insular activation during reorienting, and less fronto-striatal activation for executive control. ADHD symptom severity was associated with dysregulation of the blood oxygen level dependent (BOLD) signal within the putamen during reorienting and executive control. CONCLUSIONS Our results demonstrated altered brain mechanism in ADHD associated with all three attentional networks investigated. For alerting and executive attention, our data indicate a deviant mechanism of cortical control, while ADHD children may have adopted altered strategies for reorienting of attention. Our results also stress the etiological role of functional abnormalities in the putamen in medication-naive ADHD.

Prospective 10‐year Follow‐up in Adolescent Anorexia Nervosa—Course, Outcome, Psychiatric Comorbidity, and Psychosocial Adaptation

The aim of the present study was to follow up the long-term course of adolescent-onset anorexia nervosa by repeated assessment, to analyze the association between the course of the eating disorder and psychiatric comorbidity, and to evaluate psychosocial outcome. The sample consisted of 39 inpatients who were reinvestigated 3, 7, and 10 years after discharge. The patients and 39 controls matched for age, gender, and occupational status were assessed with structured interviews on DSM-III-R eating disorders, additional axis I and axis II psychiatric disorders, and psychosocial functioning. Results showed that 69 % of the original subjects met the criteria for full recovery at the 10-year follow-up. One patient (3%) still exhibited the full syndrome of restrictive anorexia nervosa, two patients (5%) the full syndrome of bulimia nervosa. None of the patients had died. Of the subjects, 51% currently had an axis I psychiatric disorder and 23% met the full criteria for a personality disorder. Apart from the eating disorder, anxiety disorders and avoidant-dependent and obsessive-compulsive personality disorders were the most common psychiatric diagnoses. There was a significant association between psychiatric comorbidity and the outcome of the eating disorder and between outcome and psychosocial adaptation. With regard to psychiatric morbidity and psychosocial functioning, long-term recovered patients did not differ significantly from normal controls. It is concluded that in most patients adolescent anorexia nervosa takes a prolonged course, although it seems to be more favorable than in adult-onset forms. Those who achieve complete recovery from the eating disorder have a good chance of overcoming other psychiatric disorders and to adapt to social requirements.

Social class, parental education, and obesity prevalence in a study of six-year-old children in Germany

OBJECTIVE:To assess the association between socioeconomic status (SES) and childhood obesity, and which factor in particular stands out in relation to obesity.METHODS:When 2020 children attended their obligatory health exam prior to school entry in the City of Aachen, Germany, 1979 parents (97.9%) filled out a questionnaire on their childs weight development and on indicators of their familys SES in a cross-sectional survey. In addition, standardized measures of weight and height were taken. More detailed information on several different SES variables, such as parental education, occupation, income, family constellation, single parenthood, and the location and size of the family residence was obtained by personal interviews in a subsample of all native German speaking children with a BMI≥85th percentile, defined as cases (n=146), and with a BMI between the 40th and 60th percentile, defined as controls (n=221).RESULTS:The indicators of parental education were most strongly associated with childrens obesity. There was a strong dose–response relationship between a composed index of social class and obesity. Children of the lowest social status had a more than three-fold risk to be obese than children of the highest social status in the screening population (OR: 3.29, CI: 1.92–5.63).CONCLUSIONS:The findings established a strong relationship between parental years of education and childhood obesity. Prevention and treatment programs should endeavor to better target undereducated parents and their young children at high risk.

Development of attentional networks: an fMRI study with children and adults.

Data on the development of the attentional systems remain scarce. We used structural and event-related functional magnetic resonance imaging to investigate differences in the neural mechanisms associated with alerting, reorienting, and executive control of attention between children (ages 8 to 12 years) and adults, while controlling for effects of performance and brain morphology. Behaviorally, children exhibited a numerically smaller alerting effect and significantly larger invalidity (reorienting) and interference (executive control of attention) effects. Neurally, children showed significantly reduced brain activation in a priori defined regions-of-interest in right-sided frontal-midbrain regions during alerting, in the right-sided temporo-parietal junction during reorienting of attention, and in the dorsolateral prefrontal cortex during executive control of attention. In addition, children activated significantly more brain regions outside the a priori defined regions-of-interest, such as the superior frontal gyrus during reorienting and the superior temporal gyrus during executive control of attention. Functional group differences overlapped with structural group differences in gray matter volume in particular within the frontopolar areas. The data suggest that there is a transition from functional yet immature systems supporting attentional functions in children to the more definitive adult networks and that the differences observed may reflect both developmental changes in cognitive strategies and morphology.

Morphometric brain abnormalities in boys with conduct disorder.

OBJECTIVE 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. METHOD 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. RESULTS 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 and widespread gray matter abnormalities in the frontoparietal and temporal cortices. By contrast, CD symptoms correlated primarily with gray matter reductions in limbic brain structures. CONCLUSIONS The data suggest that boys with CD and comorbid attention-deficit/hyperactivity disorder show brain abnormalities in frontolimbic areas that resemble structural brain deficits, which are typically observed in adults with antisocial behavior.

Hyperactivity in patients with anorexia nervosa and in semistarved rats: evidence for a pivotal role of hypoleptinemia.

Patients with anorexia nervosa (AN) often show normal to elevated physical activity levels despite severe weight loss and emaciation. This is seemingly in contrast to the loss of energy and fatigue characteristic of other starvation states associated with weight loss. Despite the fact that historical accounts and clinical case studies of AN have regularly commented on the elevated activity levels, the behavior has become only recently the subject of systematic study. Because rodents and other species increase their activity upon food restriction leading to weight loss when given access to an activity wheel--a phenomenon referred to as activity-based anorexia or semi-starvation-induced hyperactivity (SIH)-it has been proposed that the hyperactivity in AN patients may reflect the mobilization of phylogenetically old pathways in individuals predisposed to AN. Exogeneous application of leptin in this animal model of AN has recently been shown to suppress completely the development of SIH. Hypoleptinemia, as a result of the food restriction, may represent the initial trigger for the increased activity levels in AN patients and in food-restricted rats. In the first and second parts of our review, we will summarize the relevant findings pertaining to hyperactivity in AN patients and in the rat model, respectively. We conclude with a synopsis and implications for future research.

Structured Interview for Anorexic and Bulimic disorders for DSM-IV and ICD-10: updated (third) revision.

OBJECTIVES Earlier versions of the Structured Interview for Anorexic and Bulimic Disorders (SIAB) were modified in order to include new research findings and to update the expert rating interview to the diagnostic criteria of DSM-IV and ICD-10. The semistandardized interview was developed for reliable and valid assessment of the specific as well as the general psychopathology of eating disorders. METHOD Data from SIAB-EX interviews (current and past/lifetime symptom expression) were available from three samples: (a) 330 eating-disordered patients assessed at the start of treatment, (b) 148 former eating-disordered patients with anorexia nervosa (AN) or bulimia nervosa (BN) assessed at follow-up, and (c) 111 community controls. Sixty-one of the 87 items of the SIAB-EX with a 5-point scale were factor analyzed. RESULTS Principal components analyses with varimax rotation produced the following six components of the SIAB-EX (lifetime): (I) Body Image and Slimness Ideal; (II) General Psychopathology; (III) Sexuality and Social Integration; (IV) Bulimic Symptoms; (V) Measures to Counteract Weight Gain, Fasting, and Substance Abuse; and (VI) Atypical Binges. The factor solution for the current symptom expression was very similar to that based on lifetime symptom expression. Average item and factor scores are given for six groups of eating-disordered patients and controls. High interrater reliability was established for both current and the past symptom expression. Cronbachs alpha coefficients indicated good internal consistency for five of the six components of the SIAB-EX. DSM-IV and ICD-10 diagnoses for eating disorders can be derived directly or by using a computer algorithm from the SIAB-EX. A detailed 90-page manual facilitates the training of interviewers. CONCLUSION The 87-item SIAB-EX was originally developed for detailed assessment of eating disorders cross-sectionally and longitudinally. The updated version which allows for diagnosis according to DSM-IV and ICD-10 is described here.

Prevalence of mental health problems among children and adolescents in Germany: results of the BELLA study within the National Health Interview and Examination Survey.

BackgroundOver the past decades the public health relevance of mental health conditions in children and adolescents has been of growing concern. However, so far no detailed epidemiological data has been available for a representative national sample in Germany.ObjectivesThe present paper reports prevalence rates of general and specific mental health problems among children and adolescents in Germany and describes the link between symptoms and impairment as well as the treatment situation.MethodsThe mental health module (BELLA study) examines mental health problems in a representative sub-sample of 2,863 families with children aged 7–17 from the National Health Interview and Examination Survey among Children and Adolescents (KiGGS). Mental health problems were determined using the extended version of the strengths and difficulties questionnaire (SDQ). Further standardised screening measures were employed to screen for anxiety disorders (SCARED), conduct disorder (CBCL), attention deficit-/hyperactivity disorder (FBB-HKS, Conners’ Scale) and depressive disorders (CES-DC). Furthermore, substance abuse and suicidal tendencies were assessed. Health-related quality of life (HRQoL) and health care use were determined.ResultsOverall, 14.5% of the children and adolescents aged 7–17 fulfilled the criteria for at least one specific mental health problem associated with impairment, or had an overall mental health problem indicated by an abnormal SDQ score and present impairment. However, high comorbidity was found in the children concerned. Symptoms of overall mental health problems were present in 8.6% of the children and 6.6% of the adolescents. This number was reduced to prevalence rates of 6.3 and 4.9% when additional impairment was taken as a criterion. Irrespective of the type of disorder, fewer than half of the children affected were reported as receiving treatment. However, for those suffering from mental health problems, large impairments in HRQoL were observed.ConclusionsThe observed prevalence of mental health problems as well as their large impact on well-being and functioning calls for early prevention. This is especially important with regard to the large decrease in HRQoL in the children and adolescents affected.

Differential Effects of Methylphenidate on Attentional Functions in Children With Attention-Deficit/Hyperactivity Disorder

OBJECTIVE To examine the effects of methylphenidate on different attentional functions and behavior in children with attention-deficit/hyperactivity disorder (ADHD). METHOD A total of 60 ADHD children aged between 8 and 12 years completed a randomized, double-blind, placebo-controlled, within-subject crossover trial with two doses of methylphenidate (0.25 and 0.5 mg/kg body weight) and placebo. A comprehensive neuropsychological test battery was applied, including tests of alertness and sustained, focused, and divided attention as well as two executive tests, the stop-signal paradigm and a visual set-shifting task. RESULTS A linear improvement was identified for both medication conditions in the alertness and focused and sustained attention task, but no significant improvement was found for divided attention. Quadratic trends were found for both executive tasks. Responders defined by behavior ratings did not differ from nonresponders. CONCLUSIONS Results indicate that attentional functions are influenced differentially by methylphenidate: intensity-dimension functions are best influenced by higher doses, executive functions by moderate doses, and selectivity-dimension functions by variable doses. In addition, divergent results from behavior rating scales and from attentional paradigms emphasize that clinicians have to decide what constitutes an appropriate clinical response. A more comprehensive assessment of attention may help to find an individually optimal dose for the treatment of attentional dysfunctions.