Candidate gene studies of antipsychotic drug efficacy and drug-induced weight gain

Abstract

Converging data suggest that the identification of the molecular variants that influence antipsychotic drug response may soon be feasible. For the most part, these studies have focused on the new atypical antipsychotic agents, particularly clozapine. Although initial data in this regard has been inconclusive, recent studies have suggested that variation in the gene that codes for the dopamine D2 receptor (DRD2) may significantly influence the clinical efficacy of a number of typical and atypical antipsychotic drugs, perhaps via a variant that influences messenger RNA (mRNA) stability and translation. Studies of antipsychotic-induced weight gain have been more consistent than studies of antipsychotic drug efficacy, perhaps because weight dysregulation represents a more powerful phenotype for genetic studies, with a specific single nucleotide polymorphism (SNP) in the 5- hydroxytryptamine 2C (5-HT2c) receptor being associated with weight gain across diverse samples. Larger, more comprehensive studies are needed to confirm these results, but taken together, they suggest that pharmacogenetic strategies may be critical towards gaining a more precise understanding of the mechanism of action of antipsychotic drugs in the treatment of schizophrenia.