Journal
PHARMACOGENOMICS
Volume 7, Issue 6, Pages 863-887Publisher
FUTURE MEDICINE LTD
DOI: 10.2217/14622416.7.6.863
Keywords
antipsychotics; genetics; neuroleptics; pharmacodynamics; pharmacogenetics; pharmacogenomics; pharmacokinetics; polymorphisms; side effects; weight gain
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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 anti psychotic-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 [1]. Candidate gene studies have produced significant findings in the 5-hydroxytryptamin 2C (5HT2C) and adrenergic alpha 2a (ADR alpha 2a) receptor genes, as well as in the leptin, guanine nucleoticle 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-amiclating moncioxygenase [PAM]). However, more efforts are needed before risk prediction and personalized medicine can be made available for antipsychotic-induced weight gain.
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