Author ORCID Identifier

https://orcid.org/0000-0001-9704-6555

Defense Date

2018

Document Type

Dissertation

Degree Name

Doctor of Philosophy

Department

Human Genetics

First Advisor

Michael Neale

Abstract

Anxiety disorders (ADs) and stress-related disorders are some of the most common psychiatric disorders in the United States. Like other c0mplex psychiatric illness, genetics and neuroimaging research has focused on understanding their underlying neurobiology. Areas within the fear-network play important roles in threat perception, fear conditioning/learning, cognitive processing, and modulation of fear responses including contextual modulation and extinction and have been implicated in ADs as well as stress disorders such as posttraumatic stress disorder (PTSD). The primary gap in the current search for underlying biological mechanisms is in whether biomarkers associated with disorders share genetic influences with the disorders they index. Therefore, the aims of this dissertation are: 1) to examine the shared etiology of PTSD and threat-related brain regions while accounting for trauma using a large sample of male twins who served in the military during the Vietnam War; 2) to elucidate the shared and specific risk factors (genetic, familial environment and unique environment) and their roles amongst fear and anxiety domains in children; and 3) to examine whether brain regions previously implicated in fear processing and anxiety are significantly associated with a genetic factor score indexing fear and anxiety measures in a child sample. Using biometrical twin modeling this dissertation produced several novel findings regarding etiology of PTSD, threat-related domains and associated brain morphometry. Analyses investigating brain morphometric differences as potential endophenotypes for PTSD provided preliminary evidence that their phenotypic association is largely accounted for by environmental influences, specifically trauma exposure. However, sample size-induced model instability limits the ability to make definitive conclusions. Examining domains of fear and anxiety in children suggested a substantial genetic overlap between the two. Finally, the incorporation of a genetic factor score derived from the results of the biometrical modeling of fear and anxiety provided preliminary evidence for a genetic relationship between fear/anxiety and brain regions of interest. Although these results should be interpreted within the context of important limitations, they provide clear evidence that additional research into the genetic relationship between brain regions and disorders with larger sample sizes is justified.

Rights

© Chelsea Sawyers

Is Part Of

VCU University Archives

Is Part Of

VCU Theses and Dissertations

Date of Submission

12-11-2018

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