A few studies, however, have not detected

significant associations between-759 T/C and clozapineinduced weight gain95-97 which may reflect the winner’s curse, but it should be noted that these studies were restricted to chronic patients with extensive prior treatment. A meta-analysis of 8 studies demonstrated a greater than 2-fold increase in risk Inhibitors,research,lifescience,medical for clinically- significant (7% to 10% or greater) weight gain from baseline selleck inhibitor associated with the C allele at this SNP.98 Analogous to the aforementioned role of RGS2 in EPS, one gene involved in intracellular signaling has been repeatedly with respect to APD-induced weight gain. GNB3 encodes a subunit of a heterotrimeric guanine nucleotide-binding Inhibitors,research,lifescience,medical protein (G protein), which integrates signals between receptors and effector proteins.99 An SNP polymorphism (C825T) in this gene has been associated with essential hypertension and obesity; this SNP is also associated with relative prevalence of a high-activity

splice variant of GNB3.100 According to a recent meta-analysis, five studies have examined effects of this SNP on APDinduced weight gain; the T allele was marginally associated with increased weight gain.101 However, this effect was consistent with its effect on Inhibitors,research,lifescience,medical BMI and other metabolic variables in the general population, so the mechanism in the context of APD treatment remains Inhibitors,research,lifescience,medical unclear. Conclusions and future directions As summarized in the preceding sections, pharmacogenetic studies have begun to converge on a few genetic variants that are replicably associated with the common APD-induced motor and metabolic side effects. However, three factors limit the ability of the field to deliver on the promise of personalized medicine Inhibitors,research,lifescience,medical at this time, and point to critical issues for the next generation of pharmacogenetic studies. First, a treating psychiatrist would be unable to use this information to offer a validated alternative,

due to the lack of pharmacogenetic head-to-head comparisons of treatment with differing mechanisms. Second, even fairly consistent single-gene results, such as those observed for DRD3 and TD, fail to provide large TCL enough effect sizes to make confident clinical decisions. In order to provide a clinically useful test, with sufficient sensitivity and specificity to make confident individual predictions, a combination of SNPs across different loci will be required. Third, the economics of conducting pharmacogenetic tests on a large clinical scale will need to be justified to payers, including the insurance companies and the federal government. In order to do so, pharmacogenetics researchers will need to quantify the beneficial economic impact of tailored prescription practices.