ORCID

https://orcid.org/0000-0002-6659-357X

Date of Award

Summer 8-15-2018

Author's School

Graduate School of Arts and Sciences

Author's Department

Biology & Biomedical Sciences (Neurosciences)

Degree Name

Doctor of Philosophy (PhD)

Degree Type

Dissertation

Abstract

Alcohol is one of the most widely used psychoactive substances and accounts for 5% of global disease burden. The goal of the present work is to help advance efforts to both identify prognostic markers of risk, and to understand the mechanisms by which alcohol consumption impacts health. Early life stress is one of the strongest predictors of mental illness, including alcohol dependence, and has been hypothesized to impact risk via modulation of striatal reward functions and reward learning. Studies examined the effect of stress on reward learning and processing, and tested for moderation by genetic and environmental risk. Results were largely null showing no impact of early life stress or acute laboratory manipulated stress on behavioral or neural indices of reward learning. There were also suggestive results indicating that genetic risk may moderate the effects of early life stress. These findings challenge suggestions that stress-induced anhedonia may underlie the pathogenic effects of stress, but must also be considered in the context of study design differences (timing of stress manipulation and magnitude of rewards used). The final study in this work took the opposite approach, identifying replicable and genetically-conferred reductions in gray matter volume of frontal gyri, which prospectively predicted alcohol use. Further, gene expression analyses in the post-mortem human frontal cortex identified replicable associations with genetic risk for alcohol consumption, which implicated changes in spliceosomal and endocytotic pathway components. These results suggest that alcohol consumption does not drive reduced brain volume, but rather that these associations are attributable to shared genetic factors.

Language

English (en)

Chair and Committee

Ryan Deanna . Bogdan Barch

Committee Members

Arpana Agrawal, Michael R. Bruchas, Erik D. Herzog, Ilya E. Monosov,

Comments

Permanent URL: 2020-08-02

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