Ethnic Variations In Anti-Depressant Response

抗抑郁反应的种族差异

• 批准号: 6539207
• 负责人: HECTOR FRANKLIN MYERS
• 金额: $ 16.76万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-09-22 至 2006-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6539207
• 关键词: African American; alleles; antidepressants; behavioral /social science research tag; biotransformation; caucasian American; clinical trials; cytochrome P450; drug adverse effect; drug metabolism; drug screening /evaluation; genetic polymorphism; human subject; human therapy evaluation; longitudinal human study; major depression; mental disorder chemotherapy; outcomes research; patient oriented research; pharmacogenetics; pharmacokinetics; racial /ethnic difference; remission /regression; serotonin transporter; social psychology

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.

描述：（由申请人提供）尽管最近取得了显著进展， 几十年来，在现代精神药物治疗中，患者在他们的 对抗抑郁药的反应，从完全缓解到完全治疗 失败不良反应通常令人烦恼，有时甚至危及生命， 对患者和临床医生来说仍然是重大的挑战。 造成这种变异性的机制仍然知之甚少。在 此外，尽管不太了解， 精神反应经常存在。领域的最新发展 药物遗传学表明，遗传因素可能占很大一部分， 这些不同的反应。特定的遗传多态性影响 5-羟色胺（SERT）系统的功能已被假定为预测 抗抑郁药的效果。类似地，基因突变已经被证明可以 对许多药物代谢的表达有显著影响， 酶，包括大多数细胞色素P-450酶（例如，CYP 2C 19和 CYP 3A 4）负责大多数抗抑郁药的生物转化。 已经发现控制这些酶的基因的多态性强烈地 与各种副作用的倾向有关。资本化 根据这些新的发展，拟议的研究将审查预测价值， 400名患者（200名非裔美国人）中的一些遗传多态性 和200名高加索人）， 西酞普兰（CIT）。据推测，突变影响的功能， SERT可预测CIT的疗效，CYP 2C 19基因多态性与CIT疗效相关 与CiT的副作用和药代动力学的关系。列入该 两个对照组，非裔美国人和高加索人，他们的基因突变 模式彼此之间差异很大，这将使我们能够研究 这些差异会影响他们的抗抑郁反应模式， 关联是可以在不同种族群体中复制的。此外，非裔美国人的 response响应to antidepressants抗抑郁药has rarely很少been studied研究in a systematic系统fashion时尚， 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， 三中心（Harbor-UCLA、UCLA/King-Drew和Cedars-Sinai医疗中心） 协作性ROl项目还应有助于弥合关键的知识差距 关于治疗非洲裔美国人患有严重 萧条