Pharmacogenetics in the treatment of schizophrenia

The goal of pharmacogenetics/pharmacogenomics research is to obtain genetic information which predicts drug efficacy and adverse effects applicable to individual patients (i.e., personalized medicine). This is of particular importance in the treatment of schizophrenia, a complex and heterogeneous disorder with multiple independent symptom dimensions (e.g., psychosis, cognitive impairment, negative symptoms) and a diversity of treatment options. Genetic markers which predict efficacy for specific types of psychopathology, cognitive impairment, or related behaviors (e.g., suicide) for specific antipsychotic drugs (APDs) would diminish the need for multiple clinical trials to find the best medication. Similarly, genetic biomarkers which identify vulnerability for particular types of adverse reactions (e.g., tardive dyskinesia, weight gain) would be of great value. Such biomarkers may also clarify the mechanism of action of APDs and facilitate new drug discovery and development. Presently, genetic biomarkers which purport to predict therapeutic response or adverse effects to specific APDs are identified. Among these are biomarkers for the enzymes which metabolize psychotropic drugs (e.g., CYP2D6, CYP1A2, CYP3A4/5); biomarkers of APD-related adverse effects (e.g., weight gain or tardive dyskinesia); and biomarkers predictive of APD response (e.g., the DRD2 gene which codes the dopamine (DA) D₂ receptor; SULT4A1-1 which is reported to predict response to olanzapine; and SV2C which is reported to predict inadequate response to olanzapine and quetiapine). Their widespread adoption will follow if successful, prospective clinical trials demonstrate improvement in clinical outcome and establish convenient and cost-effective genotyping to deliver guidance to prescriber and patient.