This competitive renewal application for a K24 will enable Dr. Kranzler to continue his career development, mentorship of beginning clinical investigators, and research in the pharmacotherapy and pharmacogenetics of alcohol dependence. The research plan includes three projects, two of which are currently funded by NIAAA and one of which is under scientific review at NIAAA. The ultimate research goal of the proposal is to synthesize psychopharmacologic and genetic methods and findings to yield a coherent pharmacogenetic approach to the etiology and treatment of alcoholism. The specific research aims of the proposal are to 1) complete data collection, analysis, and report preparation for a placebo-controlled study of targeted naltrexone for problem drinkers, 2) complete data collection, analysis, and report preparation for a placebo-controlled study of sertraline for alcoholism subtypes, and 3) conduct a placebo-controlled trial of topiramate for problem drinkers. The mentoring plan will focus on the training of graduate and medical students, psychiatric residents, postdoctoral, and junior faculty to conduct patient-oriented alcohol research. The training will focus on clinical research methods, data interpretation, manuscript and grant preparation, research ethics, and human subjects protections. Mentoring will occur through trainees'participation in Dr. Kranzler's and their own research projects and through lectures and seminars offered through the Alcohol Research Center, Department of Psychiatry, and the General Clinical Research Center at the University of Connecticut School of Medicine. This range of research and educational activities offers a rich matrix of opportunities for trainees and junior investigators in patient-oriented research. The training plan identifies coursework and training experiences for Dr. Kranzler in areas that are important to Dr. Kranzler's continued development as an investigator and mentor. Over the next five years, the candidate seeks to: 1) maintain full-time effort in research and research mentoring, 2) increase the depth and breadth of his own skills through specific training in genetics, biostatistics, and bioinformatics and through continued collaboration with established experts in these areas, 3) continue the widespread dissemination of research findings through presentation at scientific meetings and publication in the scientific literature and 4) help to train the next generation of investigators who will advance the field of patient-oriented alcohol research. Relevance to public health: The proposal focuses on novel treatments for problem drinking and alcohol dependence. New findings in these areas will improve outcomes for people with these conditions. The proposal will also contribute insights into the genetic risk for alcohol dependence and moderators of treatment response, which have implications both for prevention and treatment of the disorder.

Agency
National Institute of Health (NIH)
Institute
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Type
Midcareer Investigator Award in Patient-Oriented Research (K24)
Project #
5K24AA013736-11
Application #
8261879
Study Section
Health Services Research Review Subcommittee (AA)
Program Officer
Roach, Deidra
Project Start
2002-08-01
Project End
2014-03-31
Budget Start
2012-05-01
Budget End
2014-03-31
Support Year
11
Fiscal Year
2012
Total Cost
$177,021
Indirect Cost
$13,113
Name
University of Pennsylvania
Department
Psychiatry
Type
Schools of Medicine
DUNS #
042250712
City
Philadelphia
State
PA
Country
United States
Zip Code
19104
Feinn, Richard; Curtis, Brenda; Kranzler, Henry R (2016) Balancing risk and benefit in heavy drinkers treated with topiramate: implications for personalized care. J Clin Psychiatry 77:e278-82
Lieberman, Richard; Armeli, Stephen; Scott, Denise M et al. (2016) FKBP5 genotype interacts with early life trauma to predict heavy drinking in college students. Am J Med Genet B Neuropsychiatr Genet 171:879-87
Kranzler, Henry R; Armeli, Stephen; Wetherill, Reagan et al. (2016) Self-efficacy mediates the effects of topiramate and GRIK1 genotype on drinking. Addict Biol 21:450-9
Lieberman, Richard; Kranzler, Henry R; Joshi, Pujan et al. (2015) GABRA2 Alcohol Dependence Risk Allele is Associated with Reduced Expression of Chromosome 4p12 GABAA Subunit Genes in Human Neural Cultures. Alcohol Clin Exp Res 39:1654-64
Jensen, K P; Herman, A I; Morean, M E et al. (2015) FKBP5 variation is associated with the acute and chronic effects of nicotine. Pharmacogenomics J 15:340-6
Gilbert, Jennifer; Schnoll, Robert; Morrison, Mary F et al. (2015) Smoking and Cellular Telephone Use Among Pregnant Women Seeking Prenatal Care: Opportunities for Intervention. Addict Disord Their Treat 14:203-210
Jones, Jermaine D; Comer, Sandra D; Kranzler, Henry R (2015) The pharmacogenetics of alcohol use disorder. Alcohol Clin Exp Res 39:391-402
Denis, Cécile M; Gelernter, Joel; Hart, Amy B et al. (2015) Inter-observer reliability of DSM-5 substance use disorders. Drug Alcohol Depend 153:229-35
O'Malley, Stephanie S; Corbin, William R; Leeman, Robert F et al. (2015) Reduction of alcohol drinking in young adults by naltrexone: a double-blind, placebo-controlled, randomized clinical trial of efficacy and safety. J Clin Psychiatry 76:e207-13
Chaudhary, Ninad S; Kampman, Kyle M; Kranzler, Henry R et al. (2015) Insomnia in alcohol dependent subjects is associated with greater psychosocial problem severity. Addict Behav 50:165-72

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