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. ? ?

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Midcareer Investigator Award in Patient-Oriented Research (K24)
Project #
1K24RR017365-01A1
Application #
6618815
Study Section
Special Emphasis Panel (ZRG1-BDCN-6 (01))
Program Officer
Wilde, David B
Project Start
2003-07-01
Project End
2008-05-31
Budget Start
2003-07-01
Budget End
2004-05-31
Support Year
1
Fiscal Year
2003
Total Cost
$135,698
Indirect Cost
Name
University of California Los Angeles
Department
Psychiatry
Type
Schools of Medicine
DUNS #
092530369
City
Los Angeles
State
CA
Country
United States
Zip Code
90095
Yu, Chenglong; Baune, Bernhard T; Licinio, Julio et al. (2017) Whole-genome single nucleotide variant distribution on genomic regions and its relationship to major depression. Psychiatry Res 252:75-79
Mastronardi, Claudio Alberto; Paz-Filho, Gilberto; Zanoni, Martina et al. (2015) Temporal gene expression in the hippocampus and peripheral organs to endotoxin-induced systemic inflammatory response in caspase-1-deficient mice. Neuroimmunomodulation 22:263-73
Wong, Ma-Li; Dong, Chuanhui; Flores, Deborah L et al. (2014) Clinical outcomes and genome-wide association for a brain methylation site in an antidepressant pharmacogenetics study in Mexican Americans. Am J Psychiatry 171:1297-309
Licinio, J; Negrao, A B; Wong, M-L (2014) Plasma leptin concentrations are highly correlated to emotional states throughout the day. Transl Psychiatry 4:e475
Berman, Steven M; Paz-Filho, Gilberto; Wong, Ma-Li et al. (2013) Effects of leptin deficiency and replacement on cerebellar response to food-related cues. Cerebellum 12:59-67
Wong, M-L; Dong, C; Andreev, V et al. (2012) Prediction of susceptibility to major depression by a model of interactions of multiple functional genetic variants and environmental factors. Mol Psychiatry 17:624-33
Ishibashi, K; Berman, S M; Paz-Filho, G et al. (2012) Dopamine D2/D3 receptor availability in genetically leptin-deficient patients after long-term leptin replacement. Mol Psychiatry 17:352-3
London, Edythe D; Berman, Steven M; Chakrapani, Shruthi et al. (2011) Short-term plasticity of gray matter associated with leptin deficiency and replacement. J Clin Endocrinol Metab 96:E1212-20
Mastronardi, C; Paz-Filho, G J; Valdez, E et al. (2011) Long-term body weight outcomes of antidepressant-environment interactions. Mol Psychiatry 16:265-72
Paz-Filho, Gilberto; Mastronardi, Claudio; Delibasi, Tuncay et al. (2010) Congenital leptin deficiency: diagnosis and effects of leptin replacement therapy. Arq Bras Endocrinol Metabol 54:690-7

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