Characterizing the Phenotypic and Etiological Relationships Between Executive Functions, Drinking Trajectories, and Alcohol Use Disorder Restricted; Files & ToC

Abstract

Alcohol use and disorders (AUD) are ubiquitous, yet persistent problems worldwide. Etiological studies using twins and families suggest that shared environmental factors play a key role in alcohol use initiation and early consumption. As alcohol involvement progresses over the course of development, individual differences in severity of use and problematic symptoms appear to be attributed more to genetic differences. Whole genome studies suggest that a multitude of single nucleotide polymorphisms, each of a small effect, contribute to AUD and have pleiotropic effects with other traits and diseases, such as executive functions (EF), impulsivity, and other drug use. While informative, genetic correlations using post-hoc genome-wide association study test-statistics provide limited information on how these associations manifest over development and the life course. Herein, I present two studies that examine how EF and impulsivity—key features of addiction neurobiology (i.e., preoccupation/anticipation, binge/intoxication, and withdrawal/negative affect)—relate to AUD from adolescence to early adulthood in two discrete samples. In Study 1, I leverage the neurobiological theory of addiction to examine prospective associations between individual differences in EF domains with drinking trajectories and AUD. Specifically, I employ a series of mediation models to examine the prospective associations between EF domains and a common latent factor model of lifetime AUD symptoms, as well as the extent to which that relationship is mediated by distinct drinking trajectories. Evidence from this study suggests that the probability of membership within drinking trajectory classes may not be acting mechanistically on the relationship between EF and AUD. Instead, drinking trajectories and EF act independently to predict lifetime AUD. Furthermore, twin models of the drinking trajectories suggest that likelihood of class membership is influenced primarily by shared and unique environmental influences, as opposed to genetic influences. In Study 2, I characterize the adjusted direct and indirect effects of polygenic influences from EF, impulsivity traits, alcohol consumption and AUD on the Common Latent Factor of Lifetime AUD using multi-trait polygenic models within a hierarchical multiple mediation framework. Polygenic influences from Common EF and most impulsivity traits (apart from sensation seeking) did not have a direct effect on drinking trajectories and AUD, whereas polygenic influences based on alcohol consumption and AUD diagnoses had modest direct effects that were partially independent of each other. Overall, these findings shed new light on the domains of EF across development and their effects on lifetime AUD, particularly in the context of drinking trajectories and genetic liabilities.

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About this Dissertation

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School	Laney Graduate School
Department	Psychology
Subfield / Discipline	Clinical Psychology
Degree	Ph.D.
Submission	Dissertation
Language	English
Research Field	Psychology, Clinical
关键词	executive functioning impulsivity behavioral genetics drinking trajectories alcohol use disorder
Committee Chair / Thesis Advisor	Palmer, Rohan H.C., Emory University
Committee Members	Friedman, Naomi P. , University of Colorado, Boulder Waldman, Irwin D., Emory University Walker, Elaine F., Emory University Nygaard, Lynne C., Emory University

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