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.

National Institute of Health (NIH)
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Midcareer Investigator Award in Patient-Oriented Research (K24)
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Study Section
Health Services Research Review Subcommittee (AA)
Program Officer
Roach, Deidra
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University of Pennsylvania
Schools of Medicine
United States
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Chen, Andrew C H; Davis, Christine M; Kahler, Christopher W et al. (2014) 5-HTTLPR moderates naltrexone and psychosocial treatment responses in heavy drinking men who have sex with men. Alcohol Clin Exp Res 38:2362-8
Bi, Jinbo; Gelernter, Joel; Sun, Jiangwen et al. (2014) Comparing the utility of homogeneous subtypes of cocaine use and related behaviors with DSM-IV cocaine dependence as traits for genetic association analysis. Am J Med Genet B Neuropsychiatr Genet 165B:148-56
Sartor, Carolyn E; Kranzler, Henry R; Gelernter, Joel (2014) Rate of progression from first use to dependence on cocaine or opioids: a cross-substance examination of associated demographic, psychiatric, and childhood risk factors. Addict Behav 39:473-9
Covault, Jonathan; Pond, Timothy; Feinn, Richard et al. (2014) Dutasteride reduces alcohol's sedative effects in men in a human laboratory setting and reduces drinking in the natural environment. Psychopharmacology (Berl) 231:3609-18
Quillen, Ellen E; Chen, Xiang-Ding; Almasy, Laura et al. (2014) ALDH2 is associated to alcohol dependence and is the major genetic determinant of "daily maximum drinks" in a GWAS study of an isolated rural Chinese sample. Am J Med Genet B Neuropsychiatr Genet 165B:103-10
Sun, Jiangwen; Bi, Jinbo; Kranzler, Henry R (2014) Multiview comodeling to improve subtyping and genetic association of complex diseases. IEEE J Biomed Health Inform 18:548-54
Kranzler, Henry R; Armeli, Stephen; Wetherill, Reagan et al. (2014) Self-efficacy mediates the effects of topiramate and GRIK1 genotype on drinking. Addict Biol :
Kranzler, Henry R; Covault, Jonathan; Feinn, Richard et al. (2014) Topiramate treatment for heavy drinkers: moderation by a GRIK1 polymorphism. Am J Psychiatry 171:445-52
Kranzler, Henry R (2014) Commentary on Garbutt et?al. (2014): Can we predict who benefits from naltrexone in the treatment of alcohol dependence? Addiction 109:1285-6
Kranzler, Henry R; Armeli, Stephen; Tennen, Howard et al. (2014) GRIK1 genotype and daily expectations of alcohol's positive effects moderate the reduction of heavy drinking by topiramate. Exp Clin Psychopharmacol 22:494-501

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