Genetics of antipsychotic treatment emergent weight gain in schizophrenia

Classic and modern antipsychotics can induce substantial weight gain causing diabetes, lipid abnormalities and psychological distress. Treatment emergent weight gain varies within the broad class of antipsychotics; however, an individual's propensity to develop weight gain largely depends on genetic factors. The first part of this review highlights current ideas and concepts related to antipsychotic-induced weight gain, including principles on energy homeostasis. The second part summarizes genetic findings emphasizing studies published after 2003 as prior studies have been reviewed in detail elsewhere. Candidate gene studies have produced significant findings in the 5-hydroxytryptamin 2C (5HT2C) and adrenergic alpha2a (ADRalpha2a) receptor genes, as well as in the leptin, guanine nucleotide binding protein (GNB3) and synaptomal-associated protein 25kDa (SNAP25) genes. Results from genome-wide association and linkage studies point to several chromosomal regions (e.g., 12q24) and some specific genes (e.g., promelanin concentrating hormone [PMCH], polycyctic kidney and hepatic disease 1 [PKHD1], peptidylglycine alpha-amidating monooxygenase [PAM]). However, more efforts are needed before risk prediction and personalized medicine can be made available for antipsychotic-induced weight gain.