The pharmacogenetics of antipsychotic treatment.

There is substantial interindividual variability in the effects of treatment with antipsychotic drugs not only in the emergence of adverse effects but also in symptom response. It is becoming increasingly clear that much of this variability is due to genetic factors; pharmacogenetics is the study of those factors, with the eventual goal of identifying genetic predictors of treatment effects. There have been many reported associations of single nucleotide polymorphisms (SNPs) in candidate genes with the consequences of antipsychotic drug treatment. Thus variations in dopaminergic and serotoninergic genes may influence positive and negative symptom outcome, respectively. Among the adverse effects, tardive dyskinesia and weight gain have been the most studied, with some consistent associations of functional SNPs in genes relating to pharmacological mechanisms. Technological advance has permitted large-scale genome-wide association studies (GWAS), but as yet there are few reports that replicate prior findings with candidate genes. Nevertheless, GWAS may identify associations which provide new clues relating to underlying mechanisms.