The overarching aim of this competitive renewal (K02) application is to advance my knowledge in genetics and epidemiology, and to acquire specialized skills in quantitative methodology in tandem with completing the research initiated in the first funding cycle pertaining to development and validation of a measure of substance use disorder (SUD) liability. This research has yielded a provisional liability index (LI) for quantifying SUD risk in boys at ages 10-12, 12-14, 16 and 19 and girls at ages 10-12. The LI has been shown to predict SUD between childhood and young adulthood, indicating that it may be practical for detecting high risk youths. Moreover, variation on the LI has been shown to have 79% heritability in a pilot study, indicating that it may also be a heuristic tool in SUD etiology research. Employing item response theory (IRT) methodology, in conjunction with longitudinal multivariate modeling, the provisional LI will be completed up to age 30 in males and up to age 28 in females using the data accrued by the NIDA-funded Center for Education and Drug Abuse Research (CEDAR) where I am Co-PI and Director of the Methodology and Statistics Core. During the next 5 years, the LI will additionally be cross-validated on three large datasets having appropriate item content: 1) the Collaborative Studies on the Genetics of Alcoholism (COGA), 2) the Minnesota Twin Family Study (MTFS), and, 3) the National Epidemiological Survey on Alcohol and Related Conditions. (NESARC). Following the cross-validation studies, the LI will be prepared for computer adaptive test (CAT) administration to complement the paper and pencil version. Conclusion of this task sets the stage for future R01 funding at which time I will conduct a standardization study to derive norms for the final LI versions between childhood and adulthood and to elucidate genetic mechanisms.

Public Health Relevance

Commensurate with the perspective of basic science informing practical application, this project will derive and validate an instrument - the liability index - to quantify SUD risk on a continuous scale ranging from 0-1 based on CEDAR's 19 years of empirical research into SUD etiology. Practical instruments will be developed for use across the main chronological period for detecting youths and young adults who are at high risk for use.

National Institute of Health (NIH)
National Institute on Drug Abuse (NIDA)
Research Scientist Development Award - Research (K02)
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Study Section
Human Development Research Subcommittee (NIDA)
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Weinberg, Naimah Z
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University of Pittsburgh
Schools of Pharmacy
United States
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Kirisci, Levent; Tarter, Ralph E; Reynolds, Maureen et al. (2016) Item Response Theory Analysis to Assess Dimensionality of Substance Use Disorder Abuse and Dependence Symptoms. Int J Pers Cent Med 6:260-273
Cornelius, Jack R; Chung, Tammy; Douaihy, Antoine B et al. (2016) Mirtazapine in comorbid major depression and an alcohol use disorder: A double-blind placebo-controlled pilot trial. Psychiatry Res 242:326-330
Kirisci, Levent; Vanyukov, Michael; Mezzich, Juan E (2016) Introduction to Metrics in Person Centered Medicine Research. Int J Pers Cent Med 6:248-249
Stewart, Chris; Kirisci, Levent; Long, Abigail L et al. (2015) Development and Psychometric Evaluation of the Child Neglect Questionnaire. J Interpers Violence 30:3343-66
Cornelius, Jack R; Kirisci, Levent; Reynolds, Maureen et al. (2015) Does the Transmissible Liability Index (TLI) assessed in late childhood predict suicidal symptoms at young adulthood? Am J Drug Alcohol Abuse 41:264-8
Tarter, Ralph E; Kirisci, Levent; Reynolds, Maureen et al. (2015) Longitudinal Modeling of the Association Between Transmissible Risk, Affect During Drug Use and Development of Substance Use Disorder. J Addict Med 9:464-9
Kirisci, Levent; Tarter, Ralph; Ridenour, Ty et al. (2015) Externalizing behavior and emotion dysregulation are indicators of transmissible risk for substance use disorder. Addict Behav 42:57-62
Zhai, Zu Wei; Kirisci, Levent; Tarter, Ralph E et al. (2014) Psychological dysregulation during adolescence mediates the association of parent-child attachment in childhood and substance use disorder in adulthood. Am J Drug Alcohol Abuse 40:67-74
Cornelius, Jack; Kirisci, Levent; Reynolds, Maureen et al. (2014) Does stress mediate the development of substance use disorders among youth transitioning to young adulthood? Am J Drug Alcohol Abuse 40:225-9
Cornelius, Jack R; Haas, Gretchen L; Goldstein, Gerald et al. (2014) The ""S"" Allele of the Serotonin Transporter Is Not Associated with Major Depression in a Sample OF Veterans. Adv Genet Res 12:1-10

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