Defense Date


Document Type


Degree Name

Doctor of Philosophy


Clinical and Translational Sciences

First Advisor

Danielle Dick


Risky alcohol use is a major health concern among college students, with 40.1% reporting binge drinking (5 or more drinks in one occasion) and 14.4% reporting heavy drinking (binge drinking on 5 or more occasions) in the past month. Risky alcohol use is thought to be the result of a complex interplay between genes, biological processes, and other phenotypic characteristics. Understanding this complex relationship is further complicated by known phenotypic heterogeneity in the development of alcohol use. Developmental studies have suggested two pathways to risky alcohol use, characterized by externalizing and internalizing characteristics, respectively. However, the underlying biological processes that differentiate these pathways are not fully understood. Neuroimaging studies have assessed reward sensitivity, emotion reactivity, and behavioral inhibition using fMRI and separately demonstrate associations in externalizing and internalizing disorders more broadly. In addition, previous genetic studies have found associations between specific polymorphisms and these externalizing and internalizing subtypes. Therefore, we sought further characterize the biological influences on binge drinking subtypes through the following specific aims: 1) determine the genetic relationship between externalizing and internalizing characteristics in binge drinkers, 2) test whether externalizing and internalizing binge drinkers show differences in brain activation in response to tasks measuring emotion reactivity, reward sensitivity, and behavioral inhibition. In order to achieve these aims, we conducted a series of genetic analyses assessing differences in overall SNP-based heritability and specific associated variants between the externalizing and internalizing subtypes. There were a few variants that reached genome-wide significance, the most notable being a cluster of SNPs associated with internalizing characteristics that were located in the RP3AL gene. In a subset of these binge drinking young adults, brain activation was measured on tasks assessing behavioral inhibition, reward sensitivity, and emotion reactivity. We found some preliminary differences with regard to emotion reactivity, that suggest internalizing binge drinkers are more reactive to faces overall but have blunted reaction to sad faces compared to externalizers. These findings provide an initial step to better understanding the underlying biology between the classic externalizing and internalizing alcohol use subtypes, which has the potential to elucidate new subtype specific targets for prevention and intervention.


© Megan E. Cooke

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