K02 Independent Scientist Career Development Award for Joseph F. Cubells,MD, PhD This proposal seeks support for the candidate's continued development as a research psychiatrist specializing in human genetics of drug-abuse-related phenotypes. The overarching hypothesis organizing both the Research Plan and the Career Plan is that sequence variation at specific loci will exert measurable effects on specific drug-abuse-related phenotypes. This hypothesis is predicated on the importance of identifying and characterizing appropriate phenotypes, which will reflect the effects of one or a few genes with high penetrance. Three projects are proposed in the Research Plan. Project 1, which is well under way, is the candidate's R01-funded research on the human genetics of cocaine-induced psychosis (DA 12422). The project seeks to collect DNA samples from unrelated individuals with cocaine dependence, and from family trios containing cocaine-dependent probands; these probands are carefully characterized for cocaine-induced psychotic symptoms, and for axis-1 substance-abuse and psychiatric diagnoses, as well as for plasma levels of the catecholamine-synthetic enzyme dopamine beta-hydroxylase. Project 2 will build on work accomplished in Project 1, to examine how linkage disequilbrium among nearby polymorphisms influences phenotypic variation in quantitative traits. Project 3 will elucidate genetic influences on nicotine-dependence-related phenotypes by examining the influence of functional variation at the COMT locus on human neurocognitive function and acoustic startle responses in smoking and nonsmoking subjects, with and without schizophrenia. The Career Development Plan will entail collaboration with colleagues at Yale University and the University of Connecticut, whose expertises range from evaluation of complex phenotypes, to molecular genetics, to statistical genetics. In addition, the candidate plans specific coursework, both at Yale, and at off-campus sites, to strengthen his expertise in a both molecular, statistical and clinical genetics. The latter goal will be accomplished by the candidate directing the newly-established Yale Human Behavioral Genetics Clinic, which offers psychiatric and substance-abuse services to patients with genetic illnesses.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Research Scientist Development Award - Research (K02)
Project #
7K02DA015766-02
Application #
6734225
Study Section
Human Development Research Subcommittee (NIDA)
Program Officer
Gordon, Harold
Project Start
2003-07-01
Project End
2008-06-30
Budget Start
2004-07-01
Budget End
2005-06-30
Support Year
2
Fiscal Year
2004
Total Cost
$123,225
Indirect Cost
Name
Emory University
Department
Genetics
Type
Schools of Medicine
DUNS #
066469933
City
Atlanta
State
GA
Country
United States
Zip Code
30322
Schottenfeld, Richard S; Chawarski, Marek C; Cubells, Joseph F et al. (2014) Randomized clinical trial of disulfiram for cocaine dependence or abuse during buprenorphine treatment. Drug Alcohol Depend 136:36-42
Smith, A K; Simon, J S; Gustafson, E L et al. (2012) Association of a polymorphism in the indoleamine- 2,3-dioxygenase gene and interferon-?-induced depression in patients with chronic hepatitis C. Mol Psychiatry 17:781-9
Tang, Yi-lang; Khoury, Lamya; Bradley, Bekh et al. (2011) Substance use disorders assessed using the Kreek-McHugh-Schluger-Kellogg (KMSK) scale in an urban low-income and predominantly African American sample of primary care patients. Am J Addict 20:292-9
Lori, Adriana; Tang, Yilang; O'Malley, Stephanie et al. (2011) The galanin receptor 1 gene associates with tobacco craving in smokers seeking cessation treatment. Neuropsychopharmacology 36:1412-20
Oliveto, Alison; Poling, James; Mancino, Michael J et al. (2011) Randomized, double blind, placebo-controlled trial of disulfiram for the treatment of cocaine dependence in methadone-stabilized patients. Drug Alcohol Depend 113:184-91
Khoury, Lamya; Tang, Yilang L; Bradley, Bekh et al. (2010) Substance use, childhood traumatic experience, and Posttraumatic Stress Disorder in an urban civilian population. Depress Anxiety 27:1077-86
Tang, Yi-lang; Li, Wenbiao; Mercer, Kristina et al. (2010) Genotype-controlled analysis of serum dopamine ?-hydroxylase activity in civilian post-traumatic stress disorder. Prog Neuropsychopharmacol Biol Psychiatry 34:1396-401
Ressler, Kerry J; Bradley, Bekh; Mercer, Kristina B et al. (2010) Polymorphisms in CRHR1 and the serotonin transporter loci: gene x gene x environment interactions on depressive symptoms. Am J Med Genet B Neuropsychiatr Genet 153B:812-24
Tang, Yi-lang; Kranzler, Henry R; Gelernter, Joel et al. (2009) Transient cocaine-associated behavioral symptoms rated with a new instrument, the scale for assessment of positive symptoms for cocaine-induced psychosis (SAPS-CIP). Am J Addict 18:339-45
Hodgkinson, Colin A; Yuan, Qiaoping; Xu, Ke et al. (2008) Addictions biology: haplotype-based analysis for 130 candidate genes on a single array. Alcohol Alcohol 43:505-15

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