This revised proposal requests continued support for a Comprehensive P60 Center to extend our study of antisocial drug dependence to encompass its implications for HIV/AIDS. The overall goal of this competitive renewal application is to contribute to our understanding of the etiology of individual differences in behavioral disinhibition, the relationship of this to drug abuse and the development of dependence, and the role that these play in the propensity for risky behaviors that may result in STDs, including HIV/AIDS. Our unique focus has been the contribution of genetics, both through linkage and association studies, and biometrical behavior genetic studies. Our overall thesis is that: Most new American HIV infections occur when adolescents or adults choose to engage in unprotected sexual behaviors or drug behaviors well known to be dangerous. Identifiable genes of some persons produce a lifelong behavioral disposition that involves excessive pursuit of exciting appetitive stimuli and unusual disregard of aversive consequences for behavior, a """"""""behavioral disinhibition"""""""". These characteristics frequently lead to substance abuse or dependence, antisocial behavior, and engagement in risky behaviors. Eventually, specification of the genetic and environmental factors influencing this behavioral disposition will lead to improved therapies that may reduce the vulnerability to engage in substance abuse, antisocial behavior, and risky behavior. In pursuit of this thesis we propose the following studies: 1) to identify specific genetic loci that influence behavioral disinhibition, we will conduct a genome-wide association study on an existing sample of 1000 adolescent cases and 1000 controls with Substance Dependence, Conduct Disorder, and HIV-related risk behaviors, and a newly ascertained sample of 600 adolescents recruited from adolescent substance abuse treatment programs and a control sample of 600 adolescents without serious substance or behavioral problems. 2) We will collect a third assessment in young adulthood on the clinical families and community family and twin samples participating in the Center, with detailed assessments of HIV risk behaviors. 3) We will conduct brain imaging studies to explore a neural basis for risky behaviors in disinhibited individuals, and explore the association of SNPs identified in '1'with activation of brain regions of interest, and 4) we will conduct a series of pilot studies of innovative approaches to the genetics of HIV risk behaviors. These projects will be supported by cores providing: A) Administrative, Educational, and Ethics support;B) Data management, informatics, and biostatistics;C) Genotyping and molecular genetics.

Public Health Relevance

The Center will contribute to our understanding of the etiology of individual differences in behavioral disinhibition, the relationship of this to drug abuse and the development of dependence, and the role that these play in the propensity for risky behaviors that may result in STDs, including HIV/AIDS. This new knowledge will contribute to the development of intervention strategies to reduce the risk of drug abuse, STDs, and HIV/AIDS. CENTER CHARACTERISTICS

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Comprehensive Center (P60)
Project #
5P60DA011015-15
Application #
8432508
Study Section
Special Emphasis Panel (ZDA1-RXL-E (05))
Program Officer
Lin, Yu
Project Start
1997-08-01
Project End
2014-02-28
Budget Start
2013-03-01
Budget End
2014-02-28
Support Year
15
Fiscal Year
2013
Total Cost
$2,007,203
Indirect Cost
$515,181
Name
University of Colorado at Boulder
Department
Genetics
Type
Other Domestic Higher Education
DUNS #
007431505
City
Boulder
State
CO
Country
United States
Zip Code
80309
Rhee, Soo Hyun; Friedman, Naomi P; Smith Watts, Ashley K et al. (2018) The Association Between Toddlerhood Self-Control and Later Externalizing Problems. Behav Genet 48:125-134
Huggett, Spencer B; Hatoum, Alexander S; Hewitt, John K et al. (2018) The Speed of Progression to Tobacco and Alcohol Dependence: A Twin Study. Behav Genet 48:109-124
Curry, Inga; Trim, Ryan S; Brown, Sandra A et al. (2018) Positive expectancies mediate the association between sensation seeking and marijuana outcomes in at-risk young adults: A test of the acquired preparedness model. Am J Addict :
Friedman, Naomi P; du Pont, Alta; Corley, Robin P et al. (2018) Longitudinal Relations Between Depressive Symptoms and Executive Functions From Adolescence to Early Adulthood: A Twin Study. Clin Psychol Sci 6:543-560
Yokoyama, Yoshie; Jelenkovic, Aline; Hur, Yoon-Mi et al. (2018) Genetic and environmental factors affecting birth size variation: a pooled individual-based analysis of secular trends and global geographical differences using 26 twin cohorts. Int J Epidemiol 47:1195-1206
Al-Tayyib, Alia; Riggs, Paula; Mikulich-Gilbertson, Susan et al. (2018) Prevalence of Nonmedical Use of Prescription Opioids and Association With Co-occurring Substance Use Disorders Among Adolescents in Substance Use Treatment. J Adolesc Health 62:241-244
Ellingson, Jarrod M; Corley, Robin; Hewitt, John K et al. (2018) A prospective study of alcohol involvement and the dual-systems model of adolescent risk-taking during late adolescence and emerging adulthood. Addiction :
Piirtola, Maarit; Jelenkovic, Aline; Latvala, Antti et al. (2018) Association of current and former smoking with body mass index: A study of smoking discordant twin pairs from 21 twin cohorts. PLoS One 13:e0200140
Jelenkovic, Aline; Yokoyama, Yoshie; Sund, Reijo et al. (2018) Associations between birth size and later height from infancy through adulthood: An individual based pooled analysis of 28 twin cohorts participating in the CODATwins project. Early Hum Dev 120:53-60
du Pont, Alta; Rhee, Soo Hyun; Corley, Robin P et al. (2018) Rumination and Psychopathology: Are Anger and Depressive Rumination Differentially Associated with Internalizing and Externalizing Psychopathology? Clin Psychol Sci 6:18-31

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