Ethnic Variations In Anti-Depressant Response

抗抑郁反应的种族差异

• 批准号: 6904476
• 负责人: HECTOR FRANKLIN MYERS
• 金额: $ 16.48万
• 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 2007-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6904476
• 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）尽管最近取得了显着进展 几十年来，在现代精神药物治疗中，患者的治疗方法差异很大 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， 继续给患者和临床医生带来重大挑战。 造成这种变异的机制仍然知之甚少。在 此外，尽管较少受到重视，但种族间的显着差异 精神反应经常存在。该领域的最新进展 药物遗传学表明遗传因素可能占很大一部分 这些差异的反应。影响特定基因多态性 血清素（SERT）系统的功能被假设可以预测 抗抑郁药的作用。同样，基因突变已被证明可以发挥作用 对许多药物代谢的表达有重要影响 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对 与各种副作用的倾向有关。大写 关于这些新的发展，拟议的研究将检验预测价值 400 名患者（200 名非洲裔美国人）中的一些基因多态性 和 200 名白人）患有 DSM-IV 重度抑郁症，前瞻性治疗 西酞普兰（CIT）。据推测，影响功能的突变 SERT 将预测对 CIT 的反应，CYP2CI 9 的多态性将与之相关 具有 CiT 的副作用特征和药代动力学。纳入 两个对照组，非裔美国人和白种人，他们的基因突变 模式彼此之间存在显着差异，这将使我们能够检查如何 这些差异会影响他们的抗抑郁反应模式以及是否 协会在不同种族群体之间是“可复制的”。此外，非裔美国人 很少以系统的方式研究抗抑郁药的反应， 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（Harbor-UCLA、UCLA/King-Drew 和 Cedars-Sinai 医疗中心） ROl 协作项目还应有助于弥合关键的知识差距 关于治疗患有严重疾病的非裔美国患者 沮丧。