Ethnic Variations in Antidepressant Response

描述：(申请人提供)尽管在 近几十年来，在现代精神药物治疗中，患者在 他们对抗抑郁药物的反应，从完全缓解到完全缓解 治疗失败。负面影响，经常令人烦恼，偶尔也会 危及生命，继续对患者和 临床医生。造成这种变化的机制仍然很差。 明白了。此外，尽管不那么受欢迎，但相当大的跨种族 精神药物反应的变化经常存在。中国的最新发展 药物遗传学领域表明，遗传因素可能在很大程度上解释了 这些差异在一定程度上是应对的。特定遗传多态影响 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，基因突变已经被证明是 对许多人的表达产生主要影响 药物代谢酶，包括大多数细胞色素P-450酶 (例如，CYP2C19和CYP3A4)，它们负责生物转化 大多数抗抑郁药。控制这些酶的基因的多态性有 被发现与各种疾病的倾向密切相关 副作用。利用这些新的发展，拟议的研究将 检查其中一些基因多态在400个样本中的预测价值 DSM-LV重度抑郁症患者(200名非裔美国人和200名高加索人) 西酞普兰(CIT)前瞻性治疗。据推测，突变 影响SERT功能将预测对CIT的反应，多态 CYP2C19将与副作用谱和药代动力学相关 CIT的。包括两个比较组，非洲裔美国人和 高加索人，他们的基因突变模式与 其他，将使我们能够检查这些差异如何影响他们的 抗抑郁药物的反应模式及其相关性是否可复制 跨种族。此外，非裔美国人对抗抑郁药物的反应 很少系统地研究，特别是在 对照临床试验。因此，除了解决与以下方面相关的问题 临床药物遗传学，来自这三个站点的数据(Harbor-UCLA， 加州大学洛杉矶分校\King-Drew和Cedars-Sinai医疗中心)合作R01项目 还应有助于弥合有关治疗的关键知识差距 患有严重抑郁症的非裔美国人。

DESCRIPTION: (provided by applicant) Despite remarkable progress in recentdecades in modern psychopharmacotherapy, patients vary substantially in their response to antidepressants, ranging from total remission to complete treatment failure. Adverse effects, often bothersome and occasionally life-threatening, continue to represent significant 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 factors may account for a large part of these differences in response. Specific genetic po'ymorphisms affecting the function of the serotonin (SERT) system has been postulated to predict the effect of antidepressants. Similarly, genetic mutations 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., CYP2C 19 and CYP3A4) that are responsible for the biotransformation of most antidepressants. Polymorphisms of genes controlling these enzymes have been found to be strongly associated with the propensity for various kinds 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-LV majordepression prospectively treated with citalopram (CIT). It is postulated that mutations affecting the function of SERT will predict responses to CIT, polymorphism of CYP2C 19 will be associated with the side effect profiles and pharmacokinetics of CIT. The inclusion of the two comparison groups, African Americans and Caucasians, whose genetic mutation patterns diverge significantly from each other, will allow us to examine how these differences affect their antidepressant response patterns and whether the associations are 'replicable' across ethnicity. Also, African Americans' response to antidepressants has rarely been 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 R0l project should also serve to bridge crucial knowledge gaps regarding the treatment of African American patients suffering from major depression.