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A number of theories have attempted to explicate mechanisms underpinning the transition from recreational drug use to substance dependence. A highly reliable correlate of dependence is the value ascribed to the drug. However, supernormal drug valuation may be insufficient to fully account for a subgroup of dependent individuals for whom the course of dependence is chronic and relapsing and who persist in drug use in the face of devastating costs. Three candidate secondary mechanisms for dependence are considered in this thesis: cue reactivity, cost discounting, and sensitivity to negative affect. Neither cue reactivity nor cost discounting were found to be significantly associated with severity of alcohol dependence in samples of young adult drinkers. By contrast, induced negative affect was found to be reliably associated with augmented alcohol motivation, and sensitivity to this effect was related to symptoms of depression and self-reported drinking to cope with negative affect: both risk factors for the development of dependence. These findings delineate a particular subset of dependent individuals for whom negative affect may represent a substantial trigger to continued drug use. There are a lack of brief interventions to abolish or limit negative affect driven drug motivation. This thesis trialled three potential interventions. A natural walk intervention in hazardous drinkers showed no evidence of limiting this effect in two experiments. Brief instruction in acceptance-based coping showed no evidence of limiting annoyance in response to an aversive noise induction procedure in an alcohol dependent population, and was therefore also eliminated as a potential intervention. However, engagement with pleasant environmental images, as a proxy for environmental enrichment, significantly reduced negative affect driven alcohol choice in student drinkers who reported a desire to visit the locations shown (high liking), compared to low-liking individuals and controls. This provides preliminary evidence for the efficacy of environmental enrichment type interventions, justifying further trials. In treatment of dependence more generally, interventions to increase access to healthy, non-drug sources of positive reinforcement may prove effective.

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.

The coping and alcohol literature indicates certain styles of coping are more protective against alcohol use than others. The purpose of the current study was to explore the associations among general coping styles, alcohol-specific coping skills, drinking to cope motives, and alcohol use in an effort to further examine their theoretical relationships. It was hypothesized that: (1) The relationship between problem-focused coping and alcohol use would be mediated by alcohol-specific coping, (2) Drinking to cope would mediate the relationship between avoidant emotion-focused coping and alcohol use, (3) The problem-focused coping facets of planning, active coping, suppression of competing activities, and restraint coping would contribute the most to the prediction of alcohol-specific coping skills, and (4) Intention to regulate drinking would moderate the relationship between problem-focused coping and alcohol-specific coping such that the relationship between the two would be stronger in individuals who have greater intentions of regulating their drinking. College students (N = 327) completed several self-report measures that assessed their alcohol use, general coping styles, use of alcohol-specific coping strategies, and endorsement of drinking to cope motives for alcohol use. Analyses of fully latent variables were conducted using structural equation modeling techniques. Results suggested alcohol-specific coping skills partially mediated the association between problem-focused coping and alcohol use. An unexpected positive direct association between problem-focused coping and alcohol use emerged; post-hoc analyses suggested specific facets of problem-focused coping more clearly explain that finding. The hypothesized relationships between avoidant focused coping and alcohol use were not supported but avoidant coping was significantly associated with drinking to cope, consistent with the literature. Finally, the positive association between problem-focused coping and alcohol-specific coping skills was not moderated by intentions to regulate drinking. Limitations and suggestions for future research are discussed. / Ph. D.