Malhotra Anil K, Lencz Todd, Correll Christoph U, Kane John M
Division of Psychiatry Research, The Zucker Hillside Hospital, Glen Oaks, NY 11004, USA.
Int Rev Psychiatry. 2007 Oct;19(5):523-30. doi: 10.1080/09540260701563460.
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.
精神药物反应的药物遗传学研究主要致力于确定特定候选基因的变异与药物治疗的正面和负面影响之间的关系。血清素转运体基因启动子区域多态性与抗抑郁反应之间存在显著关系，以及候选神经递质受体基因与第二代抗精神病药物反应之间存在关联，均有初步证据。精神分裂症方面的最新研究集中在首次发作、未使用过抗精神病药物的受试者，正如研究多巴胺受体基因变异和临床反应指标所表明的，这可能会提供更大的研究效力。大量新出现的文献表明，药物遗传学策略在预测药物引起的不良反应方面可能特别有用，尤其是对于抗精神病药物引起体重增加这一重要副作用。基因组学的新进展，包括全基因组基因分型方法以及有关不同人群基因组变异的全面信息，再加上DNA收集已成为常规操作的大规模临床试验，现在为新一代药物遗传学研究提供了动力。这些日益全面的方法应能提供有关与精神药物反应相关基因的信息丰富的数据，这是迈向“个性化”医学最终目标的关键一步。
