Genomics and the future of pharmacotherapy in psychiatry

Abstract

Pharmacogenetic studies of psychotropic drug response have focused on determining the relationship between variation in specific candidate genes and the positive and adverse effects of drug treatment. Preliminary evidence exists for a significant relationship between a promoter region polymorphism in the serotonin transporter gene and antidepressant response, as well as for associations between candidate neurotransmitter receptor genes and second generation antipsychotic drug response. More recent work in schizophrenia has focused on the use of first episode, antipsychotic naïve subjects, which may provide greater study power as suggested by studies examining dopamine receptor genetic variation and clinical response measures. An emerging body of literature suggests that pharmacogenetic strategies may be especially useful in the prediction of drug-induced adverse effects, in particular for the important side effect of antipsychotic-induced weight gain. New developments in genomics, including whole genome genotyping approaches and comprehensive information on genomic variation across populations, coupled with large-scale clinical trials in which DNA collection is routine, now provide the impetus for a next generation of pharmacogenetic studies. These increasingly comprehensive approaches should provide informative data on the genes associated with psychotropic drug response, a critical step towards the ultimate goal of ‘personalized’ medicine.