Pharmacogenetics of Antidepressant Drugs

描述（由申请人提供）：这是一份修订后的拨款申请，描述了一个细致的以患者为导向的研究和指导计划。私家侦探是一名医生兼科学家，在基于数据、假设驱动、以患者为导向、以实验室为基础的调查和指导方面有着出色的记录。担任UCLA GCRC核心实验室主任，《分子精神病学》（Nature Publishing）副主编，并担任UCLA转化研究研究生培训项目（K30）成员；2) UCLA神经科学跨部门项目；3)神经精神病学研究所研究理事会组)；4) UCLA GCRC顾问委员会；5)加州大学洛杉矶分校指导临床药理学研究学者计划（K12）咨询委员会P.I.是唯一准备提供临床研究培训和指导初级临床研究者。该奖项将支持PI在她自己的研究领域和临床研究的核心组成部分开发新的指导计划。这包括指导基本技能、方法、理论和概念，这些都是培养全面、独立的临床研究人员所必需的。私家侦探将在临床研究项目设计、假设发展、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、伦理和监管问题上指导年轻研究者。这项申请的一个独特之处在于，它是一项研究和指导计划，将解决少数民族临床研究人员的培训问题，并在少数民族人群中开展研究。为了解决这些问题，我们开展了一项外联工作，其中包括一个社区咨询过程，其中包括针对未被充分研究的族裔群体的一系列教育。该研究计划测试了基因多态性可能决定患者对抗抑郁药物反应的假设。这一假设将通过一项前瞻性临床IIA期随机纵向研究进行验证，该研究使用两种药理学药物（即地西帕明和氟西汀）在墨西哥裔美国族裔人群中治疗抑郁症。临床状态将通过临床访谈和汉密尔顿抑郁评定量表、贝克抑郁量表和汉密尔顿焦虑评定量表等评定。这些工具已在西班牙语中得到广泛验证。这是一项前瞻性门诊治疗研究，采用单屏蔽和双屏蔽，随机分配治疗，并通过临床措施评估结果。所有受试者将接受全面的摄入评估，然后根据我们的方案进行后续评估和治疗。这个K-24奖将使私家侦探有可能大大增加她的时间分配，以病人为导向的研究和指导初级学员和研究员在临床研究。

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.