Defense Date


Document Type


Degree Name

Doctor of Philosophy



First Advisor

Ananda Amstadter


Key variables such as trauma exposure (TE) and internalizing symptoms (e.g., posttraumatic stress disorder [PTSD]) have been shown to correlate with non-medical use of prescription drugs (NMUPD); however, the temporal associations between these phenotypes remain poorly understood. Moreover, there is a paucity of research that incorporates the influence of genetic factors in the etiology of NMUPD. Although it has been demonstrated that drug use disorders are moderately heritable, research aimed at identifying the specific genes conferring risk is virtually non-existent for NMUPD. Therefore, determining the contribution of genetic and environmental factors associated with risk is critical to understanding NMUPD. To this end, the aims of the present study included a) examination of the prevalence and longitudinal relationships between TE, probable-PTSD, and NMUPD (experimental lifetime use [E] and repeated use of 6 or more occasions [R]) via crosslag autoregressive models; and b) identification of genetic variation associated with NMUPD and PTSD via genome wide analyses (i.e., genome wide complex trait analysis [GCTA], and genome wide association analysis [GWAS]) within a sample consisting of 7,579 college students (61.1% female; Mage at baseline=18.53, SD=.65). Follow-up analyses were additionally conducted focused on interpersonal violence. The findings from the present study lends support to the extant literature suggesting that the high risk model (i.e., substance use precedes TE/PTSD) plays an important role in the longitudinal associations between NMUPD (-E, -R) and TE/probable-PTSD (prior NMUPD associated with heightened risk of TE/probable-PTSD at later time points). The h2SNP estimate derived from the meta-analysis of GCTA results for NMUPD-E was .15 (SE = .01) and for NMUPD-R was .22 (SE = .01). The h2SNP estimate for TE was .02 (SE = .01). Due to concerns regarding power, GWAS were conducted only with NMUPD-E, probable-PTSD, and IPV phenotypes. Genetic variants associated with NMUPD-E (rs73241778, rs138647543, rs142738451, rs74901044, and rs9578774) and suggestive variants associated with probable-PTSD (rs10024355) were identified following GWAS analyses. Overall, although the model suggesting that TE/PTSD precedes substance use and the role of genetic factors received limited support within the present study, it is critical to note that each of these pathways is likely important yet partially dependent on a multitude of other factors including developmental period and class of NMUPD substance being examined. Moreover, continued efforts within better powered samples are warranted to better understand the contribution of genetic factors.


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