Author ORCID Identifier


Defense Date


Document Type


Degree Name

Doctor of Philosophy


Clinical and Translational Sciences

First Advisor

Danielle M. Dick

Second Advisor

John M. Hettema

Third Advisor

Roxann Roberson-Nay


Alcohol misuse, including heavy episodic use and negative consequences, is a major public health concern and a particular problem among college students. The etiology of alcohol misuse is not well resolved, with multiple and often contradictory factors implicated in its development. Genetic factors influence alcohol misuse but few specific genes have been identified. A potential reason for these challenges is that alcohol misuse is phenotypically and genetically heterogeneous; that is, there are multiple causal pathways underlying its development. Previous typologies have suggested that distinct internalizing and externalizing pathways are involved, with corresponding differences in profiles of personality, temperament, and comorbid psychopathology. Drinking motives, specifically drinking for positive reinforcement versus negative reinforcement motives, map intuitively onto such pathways and may provide a mechanism explaining their development. The aim of this project was to utilize drinking motives as intermediate phenotypic measures to investigate genetic and environmental factors contributing to the hypothesized diverging internalizing and externalizing pathways to alcohol misuse in a prospective, longitudinal sample of college students. Mixture modeling approaches identified distinct internalizing and externalizing subgroups with both quantitative and qualitative differences in traits/symptoms. The externalizing subgroup had a broader risk profile and elevated levels of both types of drinking motives, while the internalizing subgroup had specifically elevated levels of internalizing symptoms and negative reinforcement motives. Longitudinal analyses indicated stability of drinking motives throughout college and differential associations between positive/negative reinforcement motives and internalizing, externalizing, and alcohol misuse measures. Cross-lagged structural equation models pointed to a causal direction of effect of positive reinforcement motives on alcohol misuse. Finally, a series of genetic association analyses identified some promising genes and genetic variants underlying drinking motives and internalizing psychopathology, though their genetic etiologies remain largely inconclusive. The results of this project tie together several parallel lines of research on alcohol misuse and in the broader psychiatric genetics field. Findings support the existence of distinct, though not wholly separate, internalizing and externalizing subgroups, and suggest that the intermediate mechanisms of drinking motives are a valuable tool through which to understand these heterogeneous pathways to alcohol misuse.


© Jeanne Savage

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