Weight gain is a major side effect of treatment with clozapine and other antipsychotics. Recent studies suggest an important role of the serotonin type 2C receptor gene (5-HT2CR) in antipsychotic-induced weight gain. However, investigations pertaining to a possible association between a -759C/T polymorphism (C allele) of the 5-HT2CR and weight gain induced by clozapine and/or other antipsychotics have yielded inconsistent results. We investigated the -759C/T polymorphism of the 5-HT2CR in relation to clozapine-induced change in body mass index (BMI) (kg/m) in 97 German patients with schizophrenia and found no association between the -759C allele and weight gain after 12 weeks of clozapine treatment. In addition, confounding effects of initial BMI, age, sex and duration of illness on change in BMI could not be detected by multiple linear regression analysis. Our data do not support an involvement of the -759C/T polymorphism of the 5-HT2CR in clozapine-induced weight gain in German patients with schizophrenia. Further pharmacogenetic studies pertaining to antipsychotic-induced weight gain are warranted.
We investigated serum ghrelin levels (SGL) in 12 patients with schizophrenia over a 10-week period after initiation of clozapine treatment. In contrast to increments of body mass indices (BMI, kg/m2) and serum leptin levels (SLL), no significant change in SGL was detected. Inverse correlations between delta SGL and delta SLL did not reach statistical significance. Linear mixed model analysis could not detect effects of age, sex, BMI, SLL and serum clozapine levels on SGL. Our results do not support a causal involvement of ghrelin in clozapine-related weight gain.
Computed tomography was performed in 9 male patients with a diagnosis of opiate dependence and in 9 age-matched psychiatric controls (neurotic depression). Patients with a history or diagnosis of another substance dependence (alcohol, cocaine, cannabis) were excluded from the study. The volumes of internal and external components of cerebrospinal fluid (CSF) were measured with a point-counting stereological method. Analysis of variance with age as a covariate revealed a significant enlargement of external and external CSF spaces in male patients with opiate dependence. There was no significant correlation between the length of opiate dependence and the volumes of internal and external CSF spaces. The present results suggest that opiate dependence is associated with structural brain alterations. However, the relationship between opiate dependence and structural brain changes is complex and still not well understood.
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