Biomedical subjects

B Herpertz-Dahlmann

Publications and source records attributed to B Herpertz-Dahlmann.

At least 19 recordsLinked to original sources

PubMed2007

No evidence for preferential transmission of common valine allele of the Val66Met polymorphism of the brain-derived neurotrophic factor gene (BDNF) in ADHD.

Attention deficit/hyperactivity disorder (ADHD) is a highly heritable common neurodevelopmental disorder with onset in childhood. A coding SNP (rs6265, Val66Met) of the brain-derived neurotrophic factor gene (BDNF) has recently been associated with ADHD. More specifically, paternal over-transmission of the common Val66 allele to affected children had been observed. We aimed to confirm these findings in a large, sufficiently powered, and well characterized German ADHD family sample. The Val66Met polymorphism of BDNF was genotyped in 294 families comprising one or more affected sibs (468 children). Contrary to previous reports, we did not observe over-transmission of the common Val66 allele, from either parent to affected children. We did not find support for an involvement of the Val66 allele of the Val66Met polymorphism of BDNF in the pathogenesis of ADHD in our sample.

Attention Deficit Disorder with Hyperactivity↗

PubMed2006

Weight gain associated with clozapine, olanzapine and risperidone in children and adolescents.

The study was aimed at the evaluation of weight gain associated with atypical antipsychotics and its clinical risk factors in children and adolescents. Weight and body mass index (BMI) of initially hospitalised patients treated with clozapine (n = 15), olanzapine (n = 15), and risperidone (n = 15) were prospectively monitored on a weekly basis for the first 6 weeks. Different clinical risk factors were tested for their association with weight gain in the three groups. All three groups experienced significant weight gain between baseline and endpoint (p < 0.0001). For all weight measures, planned comparisons were all significant between olanzapine vs. clozapine and risperidone, respectively. Average weight gain was significantly higher for the olanzapine group (mean = 4.6 kg, SD = 1.9) than for the risperidone (mean = 2.8 kg, SD = 1.3) and clozapine (mean = 2.5 kg, SD = 2.9) groups. Olanzapine and risperidone, but not clozapine, caused a disproportionately higher weight gain in children and adolescents in comparison to adults.

Adolescent↗

PubMed2006

Family-based association study of serotonergic candidate genes and attention-deficit/hyperactivity disorder in a German sample.

Alterations in the serotonergic pathway have been implicated in the pathogenesis of attention-deficit/hyperactivity disorder (ADHD). The aim of this study was to investigate seven genetic variants in three genes (serotonin transporter (5-HTT), serotonin receptor 1B (5-HTR1B) and serotonin receptor 2A (5-HTR2A)), which have previously been shown to be associated with ADHD. The polymorphisms under investigation were the 5-HTTLPR, the VNTR in intron 2 and the 3'UTR SNP in 5-HTT, the 5-HTR1B variations 861G>C and 102T>C, and the 5-HTR2A variations His452Tyr and 1438G>A. We genotyped these variants in a sample of 102 families with 229 children with ADHD according to DSM-IV criteria. Among the affected children, 69% fulfilled criteria for the combined type, 27% for the predominantly inattentive type, and 4% for the predominantly hyperactive-impulsive type. Associations were tested by the pedigree transmission disequilibrium test (PDT). All investigated polymorphisms in serotonergic candidate genes showed no association to ADHD in our sample. Earlier studies of these polymorphisms had also shown inconsistent results, with some studies reporting significant associations and others demonstrating no association. This discordance between studies may reflect variation in patient ascertainment criteria, genetic heterogeneity, too low statistical power for the expected effects or false positive results in the initial reports. We cannot rule out the possibility that other variations in the investigated genes contribute to the etiology of ADHD.

Adult↗

PubMed2006

The role of leptin in anorexia nervosa: clinical implications.

Leptin is a hormone with pleiotropic functions affecting several tissues. Because leptin has a crucial role in the adaptation of an organism to semi-starvation, anorexia nervosa (AN) serves as a model disorder to elucidate the functional implications of hypoleptinaemia; vice versa, several symptoms in patients with this eating disorder are related to the low leptin levels, which are characteristic of acute AN. Weight gain in AN patients can induce relative hyperleptinaemia in comparison to controls matched for body mass index; circulating leptin concentrations in AN patients thus transverse from subnormal to supranormal levels within a few weeks. We review findings on leptin secretion in AN and focus on implications, particularly for the hypothalamus-pituitary-gonadal axis, bone mineral density and physical hyperactivity. Undoubtedly, the elucidation of leptin's function as a trigger of diverse neuroendocrine adaptations to a restricted energy intake has substantially advanced our knowledge of the pathogenesis of distinct symptoms of AN, including amenorrhoea that represents one of the four diagnostic criteria. The fact that hypoleptinaemia can induce hyperactivity in a rat model for AN has led to a series of studies in AN patients, which support the notion that application of leptin to severely hyperactive patients might prove beneficial.

Animals↗

PubMed2006

[Predictors of antisocial behaviour. Peripheral psychophysiological findings in children and adults with conduct disorder].

Many studies have shown that psychophysiological parameters of processing emotional stimuli are associated with different personality traits in children, adolescents, and adults. Individuals with low autonomic baseline arousal, low orienting reaction, accelerated habituation, and reduced excitability particularly to punishing stimuli are characterised by a reduced experience of anxiety, decreased behaviour inhibition, and increased sensation seeking. These characteristics seem to raise the likelihood of dis-social behavior and are perceived as prognostically favourable for the development of antisocial personality disorders in childhood and adolescence. In contrast, an increased disposition towards anxiety, which is associated with increased autonomic reactivity, is recognised as a protective factor. Current data have shown that through special training, child and adolescent autonomic reactivity could be enhanced. Due to its versatility, this biological marker might be used for prevention in children at greater risk of developing antisocial behaviour.

Adult↗

PubMed2006

A genome-wide scan for attention-deficit/hyperactivity disorder in 155 German sib-pairs.

Three groups have previously performed genome scans in attention-deficit/hyperactivity disorder (ADHD); linkage to chromosome 5p13 was detected in all of the respective studies. In the current study, we performed a whole-genome scan with 102 German families with two or more offspring who currently fulfilled the diagnostic criteria for ADHD. Including subsequent fine mapping on chromosome 5p, a total of 523 markers were genotyped. The highest nonparametric multipoint LOD score of 2.59 (empirical genome-wide significance 0.1) was obtained for chromosome 5p at 17 cM (according to the Marshfield map). Subsequent analyses revealed (a) a higher LOD score of 3.37 at 39 cM for a quantitative severity score based on symptoms of inattention than for hyperactivity/impulsivity (LOD score of 1.11 at 59 cM), and (b) an HLOD of 4.75 (empirical genome-wide significance 0.001) based on a parametric model assuming dominant inheritance. The locus of the solute carrier 6A3 (SLC6A3; dopamine transporter 1; DAT1) localizes to 5p15.33; the gene has repeatedly been implicated in the etiology of ADHD. However, in our sample the DAT1 VNTR did not show association with ADHD. We additionally identified nominal evidence for linkage to chromosomes 6q, 7p, 9q, 11 q, 12q and 17p, which had also been identified in previous scans. Despite differences in ethnicity, ascertainment and phenotyping schemes, linkage results in ADHD appear remarkably consistent.

Adolescent↗

PubMed2005

Oculomotor inhibition in children with and without attention-deficit hyperactivity disorder (ADHD).

The aim of the present study was to distinguish between a general deficit in oculomotor control and a deficit restricted to inhibitory functions in children with attention deficit hyperactivity disorder (ADHD). In addition, we were interested in differentiating between a general inhibition deficit and deficient subfunctions of inhibition. We used a prosaccade task to measure general oculomotor abilities in 22 children with ADHD and in age- and gender-matched healthy controls. A fixation, an antisaccade and a countermanding saccade task were used to measure specific aspects of oculomotor inhibition. Two major results were obtained: First, our prosaccade task suggests similar saccadic response preparation and saccadic accuracy in the ADHD compared to the control children. Secondly, the fixation and the countermanding saccade task indicate deficits on measures of oculomotor inhibition in the ADHD group. While patients were specifically impaired in stopping an already initiated response or in suppressing exploratory saccades in a novel situation, inhibition of a prepotent response was not deficient. Our data thus indicate an underlying impairment in cognitive inhibition in ADHD that has been associated with prefrontal lobe functions. More specifically, as the anterior cingulate gyrus has been associated with the countermanding saccade task and group differences were most pronounced in this paradigm our data are in line with imaging data stressing the importance of this cortical structure in the pathophysiology of ADHD.

Adolescent↗

PubMed2005

Mutation screen of the brain derived neurotrophic factor gene (BDNF): identification of several genetic variants and association studies in patients with obesity, eating disorders, and attention-deficit/hyperactivity disorder.

Several lines of evidence indicate an involvement of brain derived neurotrophic factor (BDNF) in body weight regulation and activity: heterozygous Bdnf knockout mice (Bdnf(+/-)) are hyperphagic, obese, and hyperactive; furthermore, central infusion of BDNF leads to severe, dose-dependent appetite suppression and weight loss in rats. We searched for the role of BDNF variants in obesity, eating disorders, and attention-deficit/hyperactivity disorder (ADHD). A mutation screen (SSCP and DHPLC) of the translated region of BDNF in 183 extremely obese children and adolescents and 187 underweight students was performed. Additionally, we genotyped two common polymorphisms (rs6265: p.V66M; c.-46C > T) in 118 patients with anorexia nervosa, 80 patients with bulimia nervosa, 88 patients with ADHD, and 96 normal weight controls. Three rare variants (c.5C > T: p.T2I; c.273G > A; c.*137A > G) and the known polymorphism (p.V66M) were identified. A role of the I2 allele in the etiology of obesity cannot be excluded. We found no association between p.V66M or the additionally genotyped variant c.-46C > T and obesity, ADHD or eating disorders. This article contains supplementary material, which may be viewed at the American Journal of Medical Genetics website at http://www.interscience.wiley.com/jpages/0148-7299:1/suppmat/index.html.

Adolescent↗

PubMed2005

[Diagnosis and therapy of post-traumatic stress disorders in childhood and adolescence. Responsibilities of the child and adolescent psychiatric trauma outpatient clinic].

This article presents an overview of the etiology, clinical characteristics, assessment, and treatment of PTSD in children and adolescents. Diagnostic criteria of DSM-IV and ICD-10 for PTSD in adults may not adequately describe this disorder especially in toddlers and preschool children, because specific PTSD symptoms may vary according to the developmental stage of the child. Prevalence of PTSD in adolescence is similar to that in adulthood. Children who exhibit high degrees of psychopathology before traumatic exposure, who are exposed to high levels of trauma for an extended period, or who directly experienced the event face a high risk to develop PTSD and other later adverse outcomes. Parental support and other social factors also emerge as strong predictors of differential risk among traumatized children. Cognitive-behavioral therapy is a well-assessed intervention strategy recommended for children and adolescents with PTSD while there are no controlled trials of pharmacological treatments. The outpatient clinic for traumatized children and adolescents of the University Clinic of Aachen is introduced and clinical characteristics of children seeking help are described. In addition, the social network and cooperating services are illustrated.

Adolescent↗

PubMed2005

[Serotonin reuptake inhibitors in children. Warnings on the administration, results analysis, and recommendations].

Recent reports and recommendations from national and international health care regulatory authorities have informed us that serotonin reuptake inhibitors (SSRI) are contraindicated as new treatment for those under 18 years of age with depressive illness. They conclude that SSRI carry the risk of increased suicide-related behavior; although there was no completed suicide. The European Medicine Agency (EMEA) and German regulatory agency (BfArM) advise that these components generally should not be used in this age group except in their other, approved indications. However, it is acknowledged that they may sometimes be chosen, depending on individual clinical needs. Based on these data, the Commission for Child and Adolescent Developmental Psychopharmacology of the German Scientific Society for Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy is trying to give recommendations for the use of SSRI in clinical practice. Recent studies demonstrate that combining SSRI with psychological treatment such as cognitive behavioral therapy may reduce the risk of suicidal behavior in depressed children and adolescents.

Child↗

PubMed2005

Depression, anxiety, and obsessionality in long-term recovered patients with adolescent-onset anorexia nervosa.

Anorexia nervosa (AN) is frequently associated with symptoms of depression, anxiety, and obsessive-compulsive behavior which also develop secondary to semistarvation. It is less certain if these symptoms persist after recovery. A few studies have already reported on high prevalence rates of anxious, depressive, and obsessive features in long-term recovered patients with AN, but several of these so called "long-term" recovered patients had only maintained weight restoration for six to twelve months. The aim of this study was to determine whether depressive, anxious, and obsessive-compulsive symptoms persist in truly long-term recovered patients (BMI 20.3+/-2.5 kg/m(2)) who no longer had any eating disorder symptoms (including weight phobia) for at least 3 years. Seventeen subjects of an AN sample (n=39) previously described in a 10-year follow-up met our strict criteria of at least 3 years of complete recovery of AN. In comparison to 39 age-, sex-, and occupation-matched healthy subjects without a history of psychiatric or eating disorder, long-term recovered patients had higher levels of depressive (p=0.002), anxious (p=0.006), and obsessive-compulsive (p=0.015) features but did not differ with regard to psychiatric morbidity and psychosocial adaptation. In conclusion, depressive, anxious, and obsessive-compulsive symptoms may be personality traits in subjects with former adolescent anorexia nervosa.

Adolescent↗

PubMed2005

A retrospective study of SSRI treatment in adolescent anorexia nervosa: insufficient evidence for efficacy.

Although selective-serotonin-reuptake-inhibitors (SSRI) have been of limited efficacy in the treatment of eating disorder psychopathology and comorbid symptoms of malnourished patients with anorexia nervosa (AN), there is recent data suggesting that SSRI may play a role in preventing relapse among weight-restored patients. Though some previous studies included patients in late adolescence, the vast majority of investigated subjects have been adults. The aim of our retrospective study was to assess the effects of SSRI treatment in partially weight-restored children and adolescents with AN. Thirty two females with AN (mean 14.5+/-1.4 years) were investigated three times during inpatient treatment and at 3- and 6-month follow-up for BMI, eating disorder psychopathology, depressive symptomology, and obsessive-compulsive symptomology. Medication history during inpatient and outpatient treatment was reconstructed at the 6-month follow-up. Nineteen patients received SSRI treatment, while 13 subjects were non-medicated. In comparison to the non-SSRI group, the SSRI group had similar BMI and obsessive-compulsive scores, but higher levels of core eating disorder psychopathology and depressive symptoms at the start of medication. Rates of re-admissions were similar in both groups (SSRI group: 36%, non-SSRI group: 31%, Phi: p=0.72). Repeated measures ANOVA revealed no significant group with time interactions for BMI-SDS (p=0.84), core eating disorder symptoms (ANIS, p=0.79), depression (DIKJ, p=0.75), and obsessive-compulsive (CY-BOCS, p=0.40) scores indicating minimal or no effects of SSRI medication on the course of these variables. In conclusion, our results challenge the efficacy of SSRI medication in the treatment of eating disorder psychopathology as well as depressive and obsessive-compulsive comorbidity in adolescent AN. Clinicians should be chary in prescribing SSRI in adolescent AN unless randomized controlled trials have proofed the benefit of these drugs.

Adolescent↗

PubMed2005

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 child's weight development and on indicators of their family's 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 > or = 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 children's 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.

Body Mass Index↗

PubMed2005

Transmission disequilibrium of polymorphic variants in the tryptophan hydroxylase-2 gene in attention-deficit/hyperactivity disorder.

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 brain, in children and adolescents with ADHD. We analyzed three single nucleotide polymorphisms (SNPs) in and downstream of the transcriptional control region of the TPH2 gene in 103 families with 225 affected children. Allelic association in families with more than one affected child was assessed using the pedigree disequilibrium test. Preferential transmissions were detected for the two SNPs in TPH2's regulatory region (rs4570625, P=0.049; rs11178997, P=0.034), but not for the third SNP in intron 2 (rs4565946, P=0.3517). Haplotype analysis revealed a strong trend of association between the regulatory region SNPs (rs4570625, rs11178997) and ADHD (P=0.064). Our results link potentially functional TPH2 variations to the pathophysiology of ADHD, and further support the relevance of 5-HT in disorders related to altered motor activity and cognitive processes.

Adolescent↗

PubMed2005

Major differences in prevalence of overweight according to nationality in preschool children living in Germany: determinants and public health implications.

AIMS: To investigate the prevalence of overweight according to nationality in preschool children living in Germany, and to establish the determinants responsible for differences in body mass index. METHODS: The study was performed within the context of the 2001/2002 obligatory health examination before school entry in the city of Aachen, Germany. Of 2020 eligible children 1979 children were recruited (participation rate: 98%). Children's height and weight were measured using a standardised protocol. The parents completed a standardised questionnaire on sociodemographic factors and possible determinants of nutritional status. Being overweight was defined according to age and sex specific reference values for German children as well as according to international reference values. RESULTS: The study population included 452 (22.9%) children with other than German nationality. Among these children the prevalence of overweight was twice as high than among German children (14.8% v 7.2%). Prevalence of most known risk factors for overweight, such as low physical activity, high consumption of soft drinks, and frequent visits to fast-food restaurants was higher in the children with other nationalities than in the German children. Multivariate analyses revealed that most of the difference in prevalence of obesity by nationality is explained by known risk factors of overweight, especially education of mother and watching TV. CONCLUSIONS: The apparent ethnic differences could be explained by two non-ethnic but socioeconomic factors. In preventing overweight in children, there is the need to identify and deal with high risk environments rather than high risk ethnic groups.

Body Mass Index↗

PubMed2004

Verbal memory and aspects of attentional control in children and adolescents with anxiety disorders or depressive disorders.

BACKGROUND: The aim was to examine basic performance on attention and memory tasks in treatment-naive children and adolescents with anxiety disorder or depressive disorder and in healthy subjects under drug-free conditions. METHODS: Basic neurocognitive performance on attention and verbal memory tasks was examined in children and adolescents with emotional disorders, between 6 and 17 years of age. A total of 34 children with an anxiety disorder, 31 children with a depressive disorder, and 33 healthy controls were assessed with a comprehensive neuropsychological test battery. All children were treatment-naive at the time of testing. Five different computerised attention tasks and the Rey Auditory-Verbal Learning Test were administered. RESULTS: A significant effect of diagnosis was found for verbal memory but not for attention. LIMITATIONS: The large age range and inclusion of different diagnoses resulted in rather inhomogeneous groups. CONCLUSION: The present study provided evidence for an undisturbed attentional performance in both patient groups and a dissociation in memory functioning between anxious and depressed children. Memory impairment was found to be specifically associated with childhood depression.

Adolescent↗

PubMed2004

Transmission disequilibrium studies in children and adolescents with obsessive-compulsive disorders pertaining to polymorphisms of genes of the serotonergic pathway.

Pharmacological and challenge study data showed an involvement of the serotonergic system in the development of obsessive-compulsive disorder (OCD). We studied transmission disequilibrium of polymorphisms in three candidate genes of the serotonergic pathway in 64 trios comprising patients with early onset OCD and both of their parents. Polymorphisms of the following genes were studied: tryptophan hydroxylase 1 (rs1800532), serotonin transporter (polymorphism in the promoter region; 5-HTTLPR) and the serotonin 1 B receptor (rs6296). This is, to our knowledge, one of the first family based association studies pertaining to children and adolescents with OCD. We did not detect transmission disequilibrium of the investigated polymorphisms in OCD. Hence, these polymorphisms do not play a major role in the genetic predisposition to early onset OCD.

Adolescent↗

PubMed2004

Age-dependent neuropsychological deficits and effects of methylphenidate in children with attention-deficit/hyperactivity disorder: a comparison of pre- and grade-school children.

OBJECTIVE: Pre-school and grade-school children diagnosed with attention-deficit/hyperactivity disorder (ADHD) were compared in their performance on computerized attention tasks. Depending on the nature of the specified attention deficit, subjects were assigned to groups of cognitive subtypes. The effects of methylphenidate (MPH) were analysed depending on age and cognitive subtype. METHOD: The preschool group comprised 45 children aged 5-7 years; the grade-school group comprised 54 children aged 8-12 years. Children were tested on placebo and on MPH (mean dose: 0.25-0.3 mg/kg body weight) employing tasks of alertness, sustained attention, focused attention, divided attention, and a cognitive conflict task. RESULTS: Both groups showed measurable attention deficits. While preschoolers were especially impaired in supervisory attention functions, grade-schoolers most frequently exhibited deficits in attention intensity and selectivity. Positive MPH effects were documented for sustained attention in both age-groups. Analysis of MPH effects in dependence on the type of attention impairment (supervisory functions vs. attention intensity/selectivity) revealed a positive relation between deficits in a specific attention domain and MPH effects. CONCLUSIONS: Age-dependent differences in attention dysfunctions might be due to brain maturational processes. Performance on computerized attention tasks was particularly improved by MPH in children with objectified attention deficits suggesting that neuropsychological diagnostics can be useful to optimise treatment outcome.

Age Factors↗