N. Barth

Serotonin transporter gene-linked polymorphic region: Allele distributions in relationship to body weight and in anorexia nervosa

Several lines of evidence implicate a role for the serotonergic system in body weight regulation and eating disorders. The magnitude and duration of postsynaptic responses to serotonin (5-HT) is directed by the transport into and release from the presynaptic neuron. Recently, a common polymorphism of a repetitive element in the region of the serotonin transporter (5-HTT) gene-linked polymorphic region (5-HTTLPR) was identified that results in a system of two common alleles. The activity of the 5-HTT, as measured in in vitro assays and in human lymphoblastoid cell lines, is dependent on the respective genotype. We thus hypothesized that this polymorphism is relevant for weight regulation in general and is possibly involved in the etiology of anorexia nervosa (AN). Allele frequencies and genotypes were determined in a total of 385 unrelated obese children, adolescents and adults, 112 underweight subjects and 96 patients with AN. Furthermore, both parents of 98 obese children and adolescents and of 55 patients with AN, respectively, were genotyped, thus allowing to test for both association and linkage. The comparison of allele frequencies between obese and underweight probands provided no evidence for a major role of the 5-HTTLPR in weight regulation. Patients with AN had allele frequencies not significantly different to those observed for obese and underweight individuals.

Epidemic obesity: are genetic factors involved via increased rates of assortative mating?

OBJECTIVE: Prevalence rates of obesity have been increasing in several countries over the past two decades. Mainly secular changes in energy intake and expenditure have been invoked to underly the increasing rates; genetic factors have not been considered because of the very recency of this phenomenon. We hypothesize that genetic factors might very well be involved via an increased rate of assortative mating between obese individuals. We speculate that the recent upsurge in social stigmatization of obese individuals underlies the hypothesized increase in assortative mating.DESIGN: To accumulate evidence for our hypothesis we analysed deduced rates of assortative mating among parents of extremely obese children and adolescents, who belonged to two different large study groups (n=201 and n=270). For this purpose we calculated parental body mass indices (BMIs) based on (a) measured current heights and weights, (b) self-reported current heights and weights, and finally (c) measured current heights and recalled weights at ages 20 and 30, respectively. BMI centiles were determined which in turn were attributed to the respective BMI decile. Deduced rates of assortative mating were evaluated in bivariate histograms of the paternal and maternal BMI deciles.RESULTS: High rates of assortative mating were observed as deduced from the bivariate histograms, which revealed a fairly consistent pattern. Thus, in the first study group almost 35% of the parental pairs had a BMI in the tenth decile; over 50% of the mothers and fathers had a BMI in this top decile. Recalled parental BMIs at ages 20 and 30 also clustered in the upper decile. These results were basically replicated in the second study group. In addition, parental loading on the tenth decile was shown to be higher for the subgroup of children and adolescents who had a BMI equal to or exceeding the highest BMI of the population-based age and gender matched control group.CONCLUSIONS: Our results indicate that assortative mating is common among parents of extremely obese children and adolescents, ascertained between 1995 and 1997. In addition, the parental loading on the tenth decile is most prominent for the most obese children. Whereas we are unable to document an increased rate of assortative mating, we interpret our results as being consistent with the hypothesis that an increased rate of assortative mating has contributed to the recent rise in obesity rates in several countries. Thus, assortative mating warrants further studies to assess its impact on obesity prevalence rates through both genetic and non-genetic mechanisms. Our results suggest that assortative mating might especially increase the rates for extreme obesity.

Screening for mutations in the neuropeptide Y Y5 receptor gene in cohorts belonging to different weight extremes

OBJECTIVE: The neuropeptide Y (NPY) Y5 receptor is presumed to be involved in the regulation of food intake.DESIGN: To investigate the possible role of this receptor in weight regulation, the whole coding region of the NPY Y5 receptor gene was screened for mutations using temperature gradient gel electrophoresis (TGGE). Detected mutations were screened in extended cohorts.STUDY COHORTS AND METHODS: Cohorts of 87 extremely obese children and adolescents, 15 underweight subjects and 25 patients with anorexia nervosa (AN) were initially screened by TGGE. Extended samples of these cohorts (160 obese children and adolescents; mean body mass index (BMI) 33.5±6.4 kg/m2, 128 underweight subjects; mean BMI 18.4±1.0 kg/m2 and 58 patients with AN; mean BMI 14.6±1.7 kg/m2) were screened to determine the frequencies of a detected mutation and a detected polymorphism in the NPY Y5 receptor gene. In addition, a previously described polymorphism in the first intron of the NPY Y1 receptor gene was analysed.RESULTS: The coding region of the NPY Y5 receptor gene encompasses one exon. A single mutation, which results in a non-conservative amino acid substitution in the first extracellular domain of the receptor (Glu-4-Ala), and one silent polymorphism (Gly-426-Gly-Gly) at nucleotide position 1278 (G→A) were detected by TGGE. Both tests for association and linkage to the NPY Y1 and NPY Y5 receptor polymorphisms were negative among all cohorts. The Glu-4-Ala mutation was found only in a single patient with AN and her mother.CONCLUSION: The results do not support a major role of the NPY Y5 receptor gene in the variability of body weight in children and adolescents.

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

Summary.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.

Induced Delusional Disorder

Induced delusional disorder (or shared paranoid disorder), also known as folie à deux, is a fairly uncommon disturbance characterized by the presence of similar psychotic symptoms in two or more individuals. Most often the symptoms are delusional. Usually the ‘primary’ case, i.e. the individual who first develops psychotic symptoms, can be distinguished from one or more ‘secondary’ cases, in whom the symptoms are induced. We discuss the concept of shared paranoid disorder and consider various aetiological, clinical and diagnostic issues related to the disturbance. We also describe a case of folie à famille, this condition being a type of shared paranoid disorder. The case involves a couple and their 12-year-old son. The boy’s father is the ‘primary’ case, whilst the boy and his mother are both ‘secondary’ cases. The boy was admitted to our child and adolescent psychiatric unit for in-patient treatment. Treatment success was moderate in terms of improving the features of folie à famille in the three individuals involved.

Brain-derived neurotrophic factor V66M polymorphism in childhood-onset obsessive–compulsive disorder

Obsessive–compulsive disorder (OCD) is characterized by recurrent, intrusive, and disturbing thoughts, as well as by repetitive stereotypic behaviour. Insight into the senseless nature of the symptoms is generally preserved. Patients try, albeit usually unsuccessfully, to suppress the obsessive thoughts and compulsive behaviours. Acting out the stereotypic behaviours reduces the anxiety generated by the obsessions and compulsions (APA, 2000). In 60% of patients OCD develops before the age of 25 yr, and onset of disease can already occur in childhood (Flament et al., 1990). Familial loading is higher in early-onset OCD, indicating that genetic factors may be of greater importance in OCD with early onset (Pauls et al., 1995).

Significant weight gains in a clinical sample of obese children and adolescents between 1985 and 1995.

OBJECTIVE: Within the past decades prevalence rates for obesity among children and adolescents have increased in different populations. The hypothesis of this study is that the degree of adiposity in clinical study cohorts of extremely obese children and adolescents increased within the past decade. DESIGN: In six different study cohorts of the time period from 1985–1995 body mass indices (BMIs) of obese children and adolescents who were treated as inpatients at a specialized children’s hospital were evaluated. For this purpose body heights, body weights, ages and sex of all inpatients of three referring agencies were retrospectively assessed biannually. RESULTS: In these six cohorts a significant BMI-increase from 1985–1995 of 1.9 kg/m2 (P<0.0001) for constant sex, age and referring agencies was found. Comparisons of the quartiles and the ninth decile in both sexes did not show any systematic increase at the first quartile. In contrast, BMI-increases at the ninth decile were approximately 5 kg/m2 for males and 2.5 kg/m2 for females. CONCLUSION: Within the decade studied a significant BMI-increase was detectable in this clinical population. This effect is especially discernible in the most extreme weight groups and in males.

Successful methylphenidate treatment of early onset extreme obesity in a child with a melanocortin-4 receptor gene mutation and attention deficit/hyperactivity disorder

We present the case report of a 2 year old boy with early onset extreme obesity (body mass index (BMI) 34.2 kg/m²; body mass index standard deviation score (BMI-SDS) 5.4) who is heterozygous for a non-conservative functionally relevant melanocortin MC(4)receptor mutation (Glu308Lys) and who also showed severe symptoms of attention deficit/hyperactivity disorder (ADHD). Treatment with the stimulant methylphenidate led to a sharp decrease of BMI to 21.8 kg/m² (BMI-SDS 2.8) within 24 months. We discuss potential mechanisms for this unusually large weight loss and suggest a potential link between the melanocortinergic and the dopaminergic systems, and the sympathetic nervous system. The potential benefit of methylphenidate in obese melanocortin MC(4)receptor mutation carriers with and without co-morbid ADHD warrants further studies.

Interaktion, Familienklima, Erziehungsziele und Erziehungspraktiken in Familien mit einem zwangskranken Kind

Interaction, Family Environment, Educational Goals and Childrearing Practices in Families with a Child Suffering from Obsessive-Compulsive Disorder Objective: The study focuses on family interactions and the upbringing environment of children and adolescents with obsessive- compulsive disorder (OCD). The degree to which the family is involved in the child’s OCD symptoms, the frequency and forms of its aggressive behavior toward family members, and features of family functioning were assessed. Patients and Methods: 23 boys and 19 girls with a mean age of 12.7 years suffering from OCD according to ICD-10 and DSM-IV criteria, as well as 40 mothers and 35 fathers participated in the study. Assessments were carried out by means of structured interviews and questionnaires. Results: 85% of the parents reported that members of the family were involved in the OCD symptoms of the affected child. Most of the children and adolescents were verbally or physically aggressive, especially toward their mother. The general family environment was not disturbed except regarding interactions specifically related to the child’s OCD symptoms. Parents and children did not report childrearing practices significantly different from the standardized values of the family inventory applied. The educational goals reported indicated a rather low educational engagement of the fathers, but again there were essentially no substantial differences compared to standardized values. Conclusions: Our study does not support reports in the literature which point to specific, undesirable educational practices of the parents of children with OCD. There were no features of upbringing indicating strict religiosity, extreme ambition, prevention of the development of the child’s autonomy, conflict avoidance or tendency to isolation on the part of the family. The family members’ significant involvement in the child’s OCD symptoms and the vehemence with which the child demands this involvement must be taken into account in the therapy of childhood OCD.

Das “zyklische Erbrechen” im Kindes- und Jugendalter

Zusammenfassung: Anhand eines Fallbeispiels eines 5,5 Jahre alten Kindes wird das Krankheitsbild des “zyklischen Erbrechens” vorgestellt. Kernsymptom dieser rezidivierenden Storung ist ein aus volligem Wohlbefinden heraus schwer zu beeinflussendes Erbrechen, welches in regelmasigen Zyklen auftritt. Die Symptomatik, die Differentialdiagnose und die Therapie dieser hauptsachlich im Kindesalter auftretenden Erkrankung wird dargestellt. Atiologisch wird die enge Verwandtschaft zur kindlichen Migrane diskutiert. Wir diskutieren kritisch die Diagnose “psychogenes Erbrechen”, die in Deutschland haufig fur Storungsbilder herangezogen wird, die dem zyklischen Erbrechen ahnlich sind.