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Genetic aspects of antipsychotic induced body weight change
Weight gain is a major side effect of clozapine and other atypical antipsychotics. The underlying reasons are unknown. Effects of antipsychotics on energy intake, such as increments in appetite and/or hunger, overeating and even binge eating episodes fulfilling DSM-IV criteria for binge eating disorder, have been reported in single cases. Formal genetic findings as well as the considerable interindividual variation of the dynamic phenotype „weight gain“ underscore the importance of genetic factors. The primary aim of pharmacogenetic approaches is the identification of predisposing gene variants based on the candidate gene approach under consideration of the known binding profiles of antipsychotics. Dopaminergic, serotonergic, histaminergic and other neurotransmitter systems are seemingly involved. Based on the current knowledge of the pathways involved in body weight regulation the genetic contribution of diverse candidate genes has been investigated. However, recent studies pertaining to a possible association between several polymorphisms in genes relevant for serotonergic (5-HT) neurotransmission and weight gain induced by clozapine and/or other antipsychotics have yielded inconsistent results.