Ethnic Variations In Anti-Depressant Response

描述：(申请人提供)尽管最近取得了显著的进展 在几十年的现代心理药物治疗中，患者在他们的 对抗抑郁药物的反应，从完全缓解到完全治疗 失败了。负面影响，通常令人烦恼，有时还会危及生命， 继续对患者和临床医生构成重大挑战。 造成这种差异的机制仍然知之甚少。在……里面 此外，尽管不太受重视，但在 精神药物反应经常存在。……领域的最新发展 药物遗传学表明遗传因素可能在很大程度上解释了 这些不同的反应。特定的遗传多态影响 5-羟色胺(SERT)系统的功能被认为可以预测 抗抑郁药的效果。同样，基因突变也被证明是有效的 对多种药物代谢产物表达的主要影响 酶，包括大多数细胞色素P-450酶(例如，CYP2C19和 对大多数抗抑郁药物的生物转化起作用。 控制这些酶的基因的多态性已经被发现是强烈的 与各种副作用的倾向有关。大写字母 关于这些新的发展，拟议的研究将检验其预测价值 在400名患者(200名非裔美国人)中发现其中一些基因多态 和200名高加索人)与DSM-IV重度抑郁症前瞻性治疗 西酞普兰(CIT)。据推测，影响细胞功能的突变 SERT将预测对CIT的反应，CYP2CI 9基因多态性将与 介绍了CiT的副作用和药代动力学。包括 两个对比群体，非裔美国人和高加索人，他们的基因突变 明显不同的模式，将使我们能够研究 这些差异会影响他们的抗抑郁反应模式，以及 这种联系可以在不同的种族群体中“复制”。此外，非洲裔美国人的 对抗抑郁药物的反应很少有系统的研究， 特别是在对照临床试验的背景下。因此，除了 解决与临床药物遗传学相关的问题，由此得出的数据 三个站点(港湾-加州大学洛杉矶分校、加州大学洛杉矶分校/国王-德鲁和雪松-西奈医疗中心) 合作的ROL项目还应有助于弥合关键的知识差距 关于非洲裔美国人患有重大疾病的治疗 抑郁症。

DESCRIPTION: (provided by applicant) Despite remarkableprogress in recent decades inmodem psychopharmacotherapy, patientsvary substantially in their response toantidepressants, ranging from total remission to complete treatment failure. Adverse effects, often bothersome and occasionally life-threatening, continue to representsignificant challenges to patients and clinicians. Mechanisms responsible for such variability remain poorly understood. In addition, although less appreciated, substantial cross-ethnic variations in psychotropic responses often exist. Recent developments in the field of pharmacogenetics indicate that genetic factorsmay account for a large part of these differences in response. Specific genetic polymorphisms affecting the function of the serotonin (SERT) system has been postulated to predict the effect ofantidepressants. Similarly, geneticmutations have been shown to exert a predominant influence on the expression of a number of drug-metabolizing enzymes, including most of the cytochrome P-450 enzymes (e.g., CYP2C19and CYP3A4) that are responsible for the biotransformation of most antidepressants. Polymorphisms ofgenes controlling these enzymes have been found to be strongly associated with the propensity for variouskinds of side effects. Capitalizing on these new developments, the proposed study will examine the predictive value of some of these genetic polymorphisms in 400 patients (200 African Americans and 200 Caucasians)with DSM-IV major depression prospectively treated with citalopram (CIT). It is postulated that mutations affecting the function of SERT will predict responses toCIT, polymorphism ofCYP2CI 9 will beassociated with the side effect profiles and pharmacokinetics ofCiT. The inclusion of the two comparison groups, African Americans and Caucasians, whose genetic mutation patterns divergesignificantly from each other,will allow us to examine how these differences affect their antidepressant response patternsand whether the associationsare 'replicable' across ethnic groups. Also,African Americans' response to antidepressants has rarelybeen studied in a systematic fashion, particularly in the Context of controlled clinical trials. Thus, in addition to addressing issues related to clinical pharmacogenetics, data derived from this three-site (Harbor-UCLA, UCLA/King-Drew and Cedars-Sinai Medical Centers) collaborative ROl project should also serve to bridge crucial knowledge gaps regarding the treatment of African American patients suffering from major depression.