Lencz Todd, Malhotra Anil K
Center for Translational Psychiatry, Feinstein Institute for Medical Research, North Shore-Long Island Jewish Health System, Glen Oaks, NY, USA.
Dialogues Clin Neurosci. 2009;11(4):405-15. doi: 10.31887/DCNS.2009.11.4/tlencz.
Currently available antipsychotic drugs (APDs) carry significant though highly variable, liability to neurologic and metabolic side effects. Pharmacogenetics approaches offer the possibility of identifying patient-specific biomarkers for predicting risk of these side effects. To date, a few single nucleotide polymorphisms (SNPs) in a handful of genes have received convergent support across multiple studies. The primary focus has been on SNPs in dopamine and serotonin receptor genes: persuasive meta-analytic evidence exists for an effect of the dopamine D2 and D3 receptor genes (DRD2 and DRD3) in risk for tardive dyskinesia (TD) and for an effect of variation at the 5-HT2C receptor gene (HTR2C) for liability to APD-induced weight gain. However, effect sizes appear to be modest, and pharmacoeconomic considerations have not been sufficiently studied, thereby limiting clinical applicability at this time. Effects of these genes and others on risk for TD, extrapyramidal side effects, hyperprolactinemia, and weight gain are reviewed in this article.
目前可用的抗精神病药物（APD）会引发明显的神经和代谢副作用，尽管其副作用程度差异很大。药物遗传学方法为识别预测这些副作用风险的患者特异性生物标志物提供了可能性。迄今为止，少数几个基因中的一些单核苷酸多态性（SNP）在多项研究中得到了一致支持。主要关注的是多巴胺和5-羟色胺受体基因中的SNP：有说服力的荟萃分析证据表明，多巴胺D2和D3受体基因（DRD2和DRD3）对迟发性运动障碍（TD）风险有影响，5-羟色胺2C受体基因（HTR2C）的变异对APD引起的体重增加风险有影响。然而，效应大小似乎较小，并且药物经济学方面的考虑尚未得到充分研究，从而限制了目前的临床应用。本文综述了这些基因及其他基因对TD风险、锥体外系副作用、高泌乳素血症和体重增加的影响。
