Pharmacogenetics of Antidepressant Drugs

描述（由申请人提供）：这是一个修订后的赠款申请，描述了一个细致的计划，以病人为导向的研究和指导。私家侦探是一位医生兼科学家，在基于数据、假设驱动、面向患者和基于实验室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，分子精神病学副主编（自然出版社），并作为成员：1）加州大学洛杉矶分校研究生培训计划在转化调查（K30）; 2）加州大学洛杉矶分校神经科学跨部门计划; 3）神经精神研究所研究理事会组）; 4）加州大学洛杉矶分校GCRC咨询委员会; 5）UCLA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在自己的研究领域和临床研究的核心组成部分中开发新的指导计划的努力。这包括指导基本技能，方法，理论和概念化，以形成全面，独立的临床研究人员。私家侦探将指导年轻的研究人员设计临床研究项目，假设开发，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的，伦理和监管问题。这项申请的独特之处之一是一项研究和指导计划，该计划将解决少数民族临床研究人员的培训和在少数民族人口中进行研究的问题。为了解决这些问题，我们已经制定了一项外展工作，其中包括一个社区协商进程，其中包括一个教育系列，以了解少数民族群体。这项研究计划验证了基因多态性可能决定患者对抗抑郁药的反应的假设。该假设将通过一项前瞻性临床IIA期随机化纵向研究进行检验，该研究使用两种药物（即地昔帕明和氟西汀），在墨西哥裔美国人人群中证实了其治疗抑郁症的疗效。将通过临床访谈和评级（如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）评估临床状态。这些文书已在西班牙文中得到广泛验证。这是一项前瞻性门诊治疗研究，采用单盲和双盲，随机分配治疗，并采用临床指标评估结局。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随访评估和治疗。这个K-24奖项将使PI成为可能。显著增加她用于以患者为导向的研究以及指导临床研究中的初级学员和研究员的时间分配。

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.