Defense Date

2021

Document Type

Dissertation

Degree Name

Doctor of Philosophy

Department

Psychology

First Advisor

Ananda B. Amstadter

Second Advisor

Scott R. Vrana

Third Advisor

Eric Benotsch

Fourth Advisor

Dace Svikis

Fifth Advisor

Kaitlin Bountress

Abstract

The college years encompass a time of vulnerability for problematic alcohol use/alcohol use disorder (AUD) and exposure to traumatic events (TE), which is a transdiagnostic risk factor for AUD, posttraumatic stress disorder (PTSD), and comorbid AUD-PTSD. However, not all who experience a TE develop these disorders, highlighting the need to identify factors that impact post-trauma outcomes. Resilience has been shown to be associated with lower alcohol consumption and related problems following TE, though the buffering effects of resilience on alcohol use have not yet been examined. Further, twin studies demonstrate that resilience is moderately heritable, but further research is needed to understand the molecular genetics of resilience (e.g., establishment of molecular heritability, identification of individual variants associated with resilience, examination of overall aggregate genetic risk in relation to AUD, PTSD, and other putative protective factors). Using data of the TE exposed subsample of a larger genetically informative longitudinal cohort study of college students (i.e., Spit for Science, N=7,367), the present study had three aims: 1) investigate the buffering effect of resilience against new onset TEs on alcohol use phenotypes; 2) identify individual variants associated with resilience, as well as examine the overall heritability of resilience and 3) examine the aggregate genetic overlap of resilience with alcohol use phenotypes, PTSD, and other protective factors using aggregate risk analyses. First, resilience was examined as a buffer against new onset TE on various alcohol use outcomes using a longitudinal path analysis framework. Findings demonstrated that resilience acts as a buffer in the wake of college onset TE against AUD symptoms, but not for alcohol consumption nor binge drinking status. Second, the genetic underpinnings of resilience were investigated by examining individual variants using genome wide association study (GWAS) analyses, and by calculating the SNP-based heritability via genome-wide complex trait analysis (GCTA). Meta-analyzed GWAS identified no SNPs meeting genome-wide significance, but revealed 9 SNPs meeting the suggestive of significance threshold that should be examined in future research with larger samples sizes. The majority of these SNPs mapped on to the SEZ6L gene, implicated in Bipolar Disorder and seizure activity, as well as a cluster of genes located on chromosome 8 associated with the metabolism of vitamins such as Vitamin B folate and Vitamin E, and as such, implicated in inflammatory response. GCTA estimated modest heritability for resilience, but the estimates did not differ significantly from zero. Lastly, polygenic risk scores (PRS) were used to examine the genetic correlation between resilience and alcohol dependence (AD), alcohol consumption, PTSD, and subjective well-being. Findings support polygenic risk for alcohol consumption as related to resilience in the EUR sub-sample only, and polygenic risk for PTSD as associated with resilience in the AFR sub-sample only. Findings are further discussed in the context of clinical implications, limitations, and future directions.


Rights

© The Author

Is Part Of

VCU University Archives

Is Part Of

VCU Theses and Dissertations

Date of Submission

8-5-2922

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