Neural Reward Functioning in Bipolar Spectrum Disorders and Substance Use Disorders: Identifying Common Mechanisms

Abstract

Bipolar spectrum disorders (BSDs) and substance use disorders (SUDs) are highly co-occurring and both are associated with dysfunction in neural networks that mediate reward processing and motivated behavior. Furthermore, despite their high comorbidity rate, limited research into their shared neural mechanisms or potential prospective risk factors exists. This study attempted to elucidate common neural pathways for these disorders, and adds to the small but growing literature on possible prospective predictors of these disorders. We employed a task-based functional magnetic resonance imaging (fMRI) study to examine regions-of-interest (ventral striatum [VS], orbitofrontal cortex [OFC], ventromedial prefrontal cortex [vmPFC], dorsolateral prefrontal cortex [dlPFC]) and connectivity (VS-OFC, VS-vmPFC, vmPFC-dlPFC) analyses to examine neural reward processing as potential predictors of future substance and mood symptoms, and to explore differences among groups of participants with and without BSDs and SUDs. Results from this study provided evidence that blunted activation in the VS and dlPFC and greater negative connectivity between the vmPFC and dlPFC, key reward and control circuits, is implicated in prospective substance use. However, we did not find evidence to support our hypothesis that reward-related neural responses predict BSD symptoms or could differentiate individuals with co-occurring BSDs and SUDs from healthy volunteers. The study highlights the importance of larger, longitudinal studies to more fully probe neurodevelopmental trajectories in mood, substance, and related disorders. We also conducted an extensive review of the neural reward literature in BSDs and SUDs to understand possible pre-existent mechanisms. Results of the review provided support for an equifinality/multifinality perspective in that similar neural reward processing dysfunctions can lead to both BSDs and SUDs and different neural reward processing abnormalities can lead to a single outcome (e.g., SUDs). Taken together, results from the dissertation address an important gap in the literature on BSD-SUD comorbidity, suggest possible shared mechanisms that predispose to both disorders, and provide a backdrop for future work in this area to inform more theoretically-targeted interventions and prevention.