Ethnic Variations In Anti-Depressant Response

抗抑郁反应的种族差异

• 批准号: 6792074
• 负责人: HECTOR FRANKLIN MYERS
• 金额: $ 16.57万
• 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/6792074
• 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：（申请人提供）尽管最近出色 数十年的Inmodem心理药物疗法，患者在其身上很大 从总缓解到完整治疗的响应tonandidepressans 失败。不良反应，通常是令人困扰的，偶尔威胁生命的， 继续对患者和临床医生面临着重要的挑战。 导致这种可变性的机制仍然很少理解。在 此外，尽管不太赞赏，但对跨种族的大量变化 经常存在精神反应。该领域的最新发展 药物遗传学表明，遗传因素可能是很大一部分 这些反应差异。特定的遗传多态性影响 已经假定5-羟色胺（SERT）系统的功能，以预测 抗氧化剂的作用。同样，遗传膨胀已被证明施加 对许多药物代谢的表达的主要影响 酶，包括大多数细胞色素P-450酶（例如，CYP2C19和 CYP3A4），负责大多数抗抑郁药的生物转化。 已发现控制这些酶的基因多态性很强 与副作用的各种态度有关。大写 在这些新的发展中，拟议的研究将研究预测价值 其中一些遗传多态性中有400名患者（200名非裔美国人 和200名高加索人）有前瞻性治疗的DSM-IV重大抑郁症 西妥位（CIT）。据推测，突变影响 SERT将预测响应tocit，cyp2ci 9的多态性将伴随 具有副作用曲线和药代动力学。包括 两个比较群体，非裔美国人和高加索人，其基因突变 模式彼此分歧很大，将使我们能够检查 这些差异会影响他们的抗抑郁反应模式，并且是否 跨种族的协会“可复制”。此外，非裔美国人的 对抗抑郁药的反应很少以系统的方式研究 特别是在受控临床试验的背景下。因此，除了 解决与临床药物遗传学有关的问题，从此得出的数据 三个站点（Harbor-Ucla，UCLA/King-Drew和Cedars-Sinai医疗中心） 协作ROL项目还应用于弥合关键知识差距 关于患有主要的非裔美国人患者的治疗 沮丧。