ETHNIC VARIATIONS IN ANTIDEPRESSANT RESPONSE IN AFRICAN AMERICANS

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得主要资金，因此可以在其他CRISP条目中表示。所列机构为中心，不一定是研究者所在机构。这项合作的多中心（King-Drew医学中心，Harbor-UCLA医学中心和Cedars-Sinai医学中心）研究的目的是检查200名非洲裔美国人和200名高加索人受试者的遗传多态性的遗传价值，这些受试者在接受抗抑郁药西妥普兰（CIT）治疗时符合DSM-IV重度抑郁症标准。分子生物学和药物遗传学的最新进展极大地促进了对细胞色素P-450酶以及神经递质转运蛋白（大多数抗抑郁药的治疗靶点）的药物遗传学的遗传控制的理解，现在可以使用工具使我们能够系统地响应（kalow，1992; Lin et al.，1993年）。为了实现这些目标，本申请提出对西酞普兰（Celexa）（CIT）的安全性和有效性进行前瞻性临床试验，CIT是目前在美国市场上可获得的最具选择性的5-羟色胺再摄取抑制剂（SSRI）（斯塔尔，1998）。CIT生物转化由CYP 2C 19介导（Catterson & Preskorn，1996）。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The purpose of this collaborative, multi-site (King-Drew Medical Center, Harbor-UCLA Medical Center and Cedars-Sinai Medical Center) study is to examine the predective value of genetic polymorphism in 200 African American and 200 Caucasina subject who meet DSM-IV criteria for major depression when treated with the antidepressant citolopram (CIT). Recent advances in molecular biology and pharmacogenetics have contributed substantially to the understanding of the genetic control of the pharmacogenetics of the cytochrome P-450 enzymes, as well as the neurotransmitter transporters (therapeutic targets of most antidepressants), tools are now available to enable us to systematically response (kalow, 1992; Lin et al., 1993). In order to pursue these goals, this application proposes to contuct a prospective clinical trail of the safety and efficacy of citalopram (Celexa) (CIT), which is the most selective serotonin reuptake inhibitor (SSRI) that is currently available on the U.S. market (Stahl, 1998). CIT biotransformation is mediated pimarilty by CYP2C19 (Catterson & Preskorn, 1996).