Pharmacogenomics Applications in Psychiatric Disorders

Serious mental illnesses, including schizophrenia and major depressive disorder, result in considerable chronicity, morbidity, and mortality, and are amongst the leading causes of disability in the developed world. Despite advances in development of pharmacologic agents over the last two decades, only about one-third of patients with psychotic or affective disorders experience rapid or robust treatment response, while as many as 40–50% can be labeled as partially or com pletely treatment refractory. Pharmacogenetic studies offer the potential to enhance clinical prognosis, and ultimately to tailor individualized therapies; however, the psychiatric pharmacogenetic literature to date may give the appearance of diverse, unreplicated results of uncertain clinical significance. To overcome this impression, we review findings demonstrating a replicable role in clinical prediction#x2014;for both symptom response and side effect burden—of several polymorphisms in genes in the serotonin and dopamine systems. We also highlight the limitations in current research, including the role of ethnic heterogeneity, the need to study treatment-na� patients, the lack of cost-benefit pharmacoeconomic studies, and the need for more comprehensive genotyping/haplotyping. We conclude by demonstrating the potential role of novel technologies, specifically whole genome association, in identifying robust, novel loci for pharmacogenomic prediction.