Pharmacogenetics of Antidepressant Drugs

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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.