Developing and Evaluating a Positive Valence Treatment for Alcohol Use Disorder with Anxiety or Depression

PROJECT SUMMARY Only 20-30% of individuals with alcohol use disorder (AUD) exhibit long-term benefits with leading pharmacologic (e.g., acamprosate, naltrexone) and behavioral therapies (e.g., cognitive behavioral therapy, contingency management). Nearly half of individuals seeking treatment for AUD experience clinically significant anxiety and depression symptoms (ANX/DEP), which relate to worse long-term outcomes. Positive valence system (PVS) dysfunction is a common and pernicious feature of both AUD and ANX/DEP that is predictive of poor functioning and prognosis. Although PVS dysfunction represents a shared pathophysiologic mechanism across AUD and ANX/DEP, it is not sufficiently targeted by existing treatments. Our team developed a behavioral intervention, Amplification of Positivity (AMP), to enhance PVS function through increasing exposure and responsivity to non-drug rewards. In our previous work, AMP was found to increase positive valence outcomes (e.g., positive affect, social connectedness, life satisfaction), enhance reactivity of PVS neural circuits (i.e., striatal response to social reward), and decrease negative valence outcomes and symptoms for individuals with ANX/DEP. We have begun to modify this intervention for the treatment of co-occurring AUD and ANX/DEP (AMP-A), completing an initial pilot feasibility study. For the proposed study, we will further develop and refine AMP-A based upon qualitative and quantitative feedback from clinicians and participants and complete a pilot study of the protocol with eight individuals diagnosed with AUD and reporting clinically elevated ANX/DEP symptoms - further refining the protocol based on feedback from this pilot. We will then recruit 60 individuals with AUD+ANX/DEP and randomize them to complete AMP-A or cognitive behavioral therapy (CBT) – a first-line treatment for AUD that has small effects on the PVS. All participants will complete clinical and self-report measures before, during and after therapy and at 3-month follow-up. This project will accomplish the following aims: (1) Further develop and refine AMP-A to optimize its acceptability and potential clinical utility; (2) Determine the effects of AMP-A compared to CBT on the PVS, as measured by self-report of positive affect, social connectedness, well-being, and reward processing; (3) Determine whether increases in PVS function are associated with greater clinical improvement of alcohol use, anxiety, and depression. Results will have important implications for the treatment of AUD and co-occurring anxiety or depression by determining the utility of directly targeting the PVS, which will pave the way for future research seeking to remediate the harmful effects of these conditions.