Genetic variation of the ghrelin activator gene ghrelin O-acyltransferase (GOAT) is associated with anorexia nervosa.

The gastrointestinal peptide hormone ghrelin promotes food intake and increases body weight and adiposity through activation of the growth hormone secretagogue receptor (GHSR1a). To promote its biological action ghrelin is acylated at its serine 3 residue by the recently discovered ghrelin O-acyltransferase (GOAT, a.k.a. membrane-bound O-acyltransferase 4, MBOAT4). Plasma levels of total and acyl-ghrelin are negatively correlated with body-mass-index (BMI); as lower the BMI as higher plasma levels of total and acylated ghrelin and vice versa. Accordingly, plasma levels of total and acyl-ghrelin are elevated in patients with anorexia nervosa (AN) and decline upon weight regain. The importance of the endogenous Goat/ghrelin system in the neuroendocrine adaptation to fasting was recently highlighted by the observation that acyl-ghrelin mediated elevation of growth hormone (GH) release prevents starvation induced hypoglycemia in Goat(-/-) mice. The aim of this study was to test if genetic variation of GOAT is implicated in the etiology of AN. We therefore assessed association of 6 tagging single nucleotide polymorphisms (tagSNPs), which were predicted to cover 96% the common genetic variability of GOAT plus 50 kb of the 5' and 3' flanking region, in 543 German patients with AN and 612 German normal and underweight healthy controls. Based on a recessive mode of inheritance we observed some evidence for association of the G/G genotype at SNP rs10096097 with AN (nominal two-sided p = 0.031). Based on our results we conclude that genetic variation in GOAT might be implicated in the etiology of AN.

Expression analyses of the mitochondrial complex I 75-kDa subunit in early onset schizophrenia and autism spectrum disorder: increased levels as a potential biomarker for early onset schizophrenia.

Searching for a peripheral biological marker for schizophrenia, we previously reported on elevated mitochondrial complex I 75-kDa subunit mRNA-blood concentrations in early onset schizophrenia (EOS). The aim of this study was to further evaluate the utility of this gene as a potential marker for schizophrenia. Both-schizophrenia and autism-are suggested to be neuronal maldevelopmental disorders with reports of mitochondrial dysfunction and increased oxidative stress. Therefore we have investigated the expression levels of mitochondrial complex I 75-kDa subunit mRNA in whole blood of children with autistic spectrum disorder (ASD) and a group of adolescent acute first-episode EOS patients in comparison to matched controls. We have found that compared to the respective controls only the group of EOS patients-and not the ASD group-showed a significantly altered expression of the complex I 75-kDa subunit mRNA. Although further studies are necessary to test for the specificity of this marker, our findings point to the potential use of the mitochondrial complex I as a biomarker for schizophrenia.

[Phenomenology and co-morbidity of childhood onset obsessive compulsive disorder]. / Phänomenologie und Komorbidität der Zwangsstörung bei Kindern und Jugendlichen.

OBJECTIVES: The goal of the study was to investigate the contents and comorbidity features of obsessive-compulsive disorder in children and adolescents. METHOD: 55 patients (29 males, 26 females), mainly inpatients selected from university clinics for child and adolescent psychiatry (95%), were investigated. Structured diagnostic interviews were used to interview patients and their parents. RESULTS: The mean age of onset for obsessive-compulsive disorders was 11.3 years. In males the onset was slightly earlier than among females, but this difference was not significantly significant. Compulsions mostly referred to washing and cleaning, checking, repeating, ordering, and counting. Most frequently, obsessions included thought about contamination, catastrophes, sexuality, and aggression. According to parental reports, the rate of comorbidity was high (lifetime diagnosis: 69%, current diagnosis: 53%), with anxiety, depressive, hyperkinetic, conduct, and eating disorders being the most frequent co-morbid conditions. Obsessive-compulsive symptoms were more intense in those patients who had a greater number of lifetime diagnoses of other psychiatric disorders. Comparing the rates found when structured interviews were carried out according to the study protocol to those for clinicians, clinicians were found to have diagnosed mixed obsessional thoughts and acts (presenting obsessional thoughts, as well as compulsive acts) less frequently. CONCLUSIONS: The results of this investigation are well in line with those of international studies on obsessive-compulsive disorders. The rates of disorders found were dependent on the diagnostic methods used. A potentially promising approach for further investigation is the sub-typing of patients according to symptom dimensions.