Trauma related drinking to cope: A phenotypic and molecular genetic investigation of the self-medication model

Posttraumatic stress disorder (PTSD) and alcohol use problems (AUP) commonly co-occur, have shared latent genetic risk, and are associated with many negative public health outcomes. Via a self-medication framework, trauma-related drinking to cope (TRD), an unexplored construct to date, may help explain why these two disorders co-occur, thus serving as an essential target for treatment and prevention efforts. The present study aimed to create a novel measure of TRD and examine its psychometric properties, investigate its indirect influences on the association between PTSD and AUP, as well as explore its potential shared molecular genetic risk with PTSD in a genetically-informative study of college students. A sample of 1,896 students with a history of trauma and alcohol use provided genotypic data and completed an online assessment battery. First, the psychometric properties of TRD and how it relates to relevant constructs were examined using descriptive statistics and structural equation modeling. Findings demonstrated support for the external validation of TRD, both with regard to PTSD and alcohol consumption and related problems, and suggested that TRD is a more specific measure of drinking to cope motives compared to the commonly used Drinking Motives Questionnaire coping subscale. Second, results from a correlated multiple mediator model indicated that, while accounting for the effects of generalized drinking motives, TRD partially mediated the relation between PTSD and AUP and that this relationship was stronger for males than for females. Results were substantiated using longitudinal data. Third, univariate and bivariate genotypic analyses were conducted for TRD and PTSD, most of which resulted in null findings likely due to insufficient sample sizes. However, genome wide association analysis identified several significant genetic variants associated with TRD in participants of European Ancestry. Genes associated with TRD included PRAME, a protein coding gene with antithetical effects to genes commonly implicated in alcohol metabolism, as well as several genes implicated in immune system functioning (e.g., IGH, IGHE, ELK2AP). Polygenic risk for PTSD was associated with PTSD in the present sample and nominally associated with TRD. Findings are discussed in the context of limitations, clinical implications, and future directions