Pharmacogenetics of Antidepressant Drugs

抗抑郁药物的药物遗传学

• 批准号: 6618815
• 负责人: MA-LI WONG
• 金额: $ 13.57万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-07-01 至 2008-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6618815
• 关键词: Mexican Americans; antidepressants; body composition; clinical research; clinical trial phase II; desipramine; drug screening /evaluation; fluoxetine; genetic polymorphism; human subject; human therapy evaluation; interview; longitudinal human study; medically underserved population; mental disorder chemotherapy; molecular genetics; patient oriented research; pharmacogenetics; pharmacokinetics; psychopharmacology

DESCRIPTION (provided by applicant): This is a revised grant application that describes a meticulous program of patient-oriented research and mentoring. The P.I. is a physician-scientist with an outstanding track record in data based, hypothesis-driven patient-oriented and laboratory based investigation, and mentoring. As the Director of the UCLA GCRC Core Lab, Associate Editor of Molecular Psychiatry (Nature Publishing), and as member of the: 1) UCLA Graduate Training Program in Translational Investigation (K30); 2) UCLA Neuroscience Interdepartmental Program; 3) Neuropsychiatric Institute Research Council Group); 4) UCLA GCRC Advisory Board; 5) UCLA Mentored Clinical Pharmacology Research Scholar Program (K12) Advisory Committee the P.I. is uniquely prepared to provide clinical research training and to mentor junior clinical investigators. This award would support the PI's efforts to develop a new mentoring program both in her own area of research and in the core components of clinical research. This includes mentoring in the fundamental skills, methodology, theories, and conceptualizations necessary for the formation of well-rounded, independent, clinical researchers. The P.I. will mentor young investigators in the design of clinical research projects, hypothesis development, clinical pharmacology and pharmacogenomics, scientific writing, and the legal, ethical and regulatory issues related to clinical research. One of the unique aspects of this application is a research and mentoring plan that will address the training of minority clinical researchers and the conduction of research in ethnically identified minority populations. To address these topics, we have developed an outreach effort that consists of a process of community consultation that includes an educational series to understudied ethnic groups. The research proposal tests the hypothesis that genetic polymorphisms might determine a patient's response to antidepressants. This hypothesis will be tested by a prospective clinical phase IIA randomized longitudinal study, using two pharmacological agents (namely Desipramine and Fluoxetine) with demonstrated efficacy in the treatment of depression, in the Mexican-American ethnic population. Clinical status will be assessed with clinical interviews and ratings such as the Hamilton Ratings Scale for Depression, Beck Depression Inventory, and Hamilton Anxiety Rating Scale. These instruments have been extensively validated in Spanish. This is a prospective outpatient treatment study with single- and double-masking, with random assignment of treatment, and with outcomes assessed with clinical measures. All subjects will undergo a comprehensive intake assessment, and will then have follow-up assessments and treatments according to our protocol. This K-24 award will make possible for the P.I. to significantly increase her time allocation for patient-oriented research and for mentoring of junior trainees and fellows in clinical research.

描述(由申请人提供)：这是一份修订后的拨款申请，描述了一项以患者为中心的研究和指导的细致计划。P.I.是一名内科科学家，在基于数据、以假设为导向、以患者为导向和以实验室为基础的调查和指导方面有着出色的记录。作为加州大学洛杉矶分校GCRC核心实验室主任、《分子精神病学》(自然出版)的副主编，以及成员：1)加州大学洛杉矶分校翻译研究研究生培训项目(K30)；2)加州大学洛杉矶分校神经科学跨部门项目；3)神经精神病学研究所研究委员会；4)加州大学洛杉矶分校GCRC顾问委员会；5)加州大学洛杉矶分校指导的临床药理学研究学者项目(K12)咨询委员会--P.I.是专门为提供临床研究培训和指导初级临床研究人员而准备的。这一奖项将支持PI在她自己的研究领域和临床研究的核心部分开发新的指导计划的努力。这包括在基本技能、方法论、理论和概念化方面的指导，这是形成全面、独立的临床研究人员所必需的。P.I.将在临床研究项目设计、假说开发、临床药理学和药物基因组学、科学写作以及与临床研究相关的法律、伦理和监管问题方面指导年轻研究人员。这一应用的一个独特方面是研究和指导计划，该计划将解决少数族裔临床研究人员的培训和在少数族裔人口中进行研究的问题。为了解决这些问题，我们开展了一项外展工作，其中包括一项社区协商进程，其中包括对未被充分研究的族裔群体进行一系列教育。这项研究提案测试了一种假设，即基因多态可能决定患者对抗抑郁药物的反应。这一假设将通过一项前瞻性的临床IIA期随机纵向研究来验证，该研究使用了两种在墨西哥裔美国人中被证明有效治疗抑郁症的药理学药物(即地塞帕明和氟西汀)。临床状况将通过临床访谈和评级进行评估，如汉密尔顿抑郁量表、贝克抑郁量表和汉密尔顿焦虑量表。这些工具在西班牙语中得到了广泛的验证。这是一项前瞻性的门诊治疗研究，采用单掩蔽法和双掩蔽法，随机分配治疗，并用临床措施评估结果。所有受试者将接受全面的入学评估，然后根据我们的方案进行后续评估和治疗。这一K-24奖项将使P.I.有可能显著增加她在以患者为导向的研究以及指导初级实习生和临床研究研究员方面的时间分配。