New findings in pharmacogenetics of schizophrenia

Purpose of reviewThis review highlights recent advances in the investigation of genetic factors for antipsychotic response and side effects.Recent findingsAntipsychotics prescribed to treat psychotic symptoms are variable in efficacy and propensity for causing side effects. The major side effects include tardive dyskinesia, antipsychotic-induced weight gain (AIWG), and clozapine-induced agranulocytosis (CIA). Several promising associations of polymorphisms in genes including HSPG2, CNR1, and DPP6 with tardive dyskinesia have been reported. In particular, a functional genetic polymorphism in SLC18A2, which is a target of recently approved tardive dyskinesia medication valbenazine, was associated with tardive dyskinesia. Similarly, several consistent findings primarily from genes modulating energy homeostasis have also been reported (e.g. MC4R, HTR2C). CIA has been consistently associated with polymorphisms in the HLA genes (HLA-DQB1 and HLA-B). The association findings between glutamate system genes and antipsychotic response require additional replications.SummaryThe findings to date are promising and provide us a better understanding of the development of side effects and response to antipsychotics. However, more comprehensive investigations in large, well characterized samples will bring us closer to clinically actionable findings.