Thursday, May 15, 2025
5/15/2025
Chronic Alcohol and Brain Stress Circuit Response - Project Abstract / Summary Alcohol use disorder (AUD) is associated with high relapse risk, and so identifying those most vulnerable to relapse and heavy drinking is critical to improve AUD outcomes. Chronic pain (CP) frequently co-occurs with AUD and promotes pain-related heavy drinking. Previous work showed significant chronic alcohol-related neuroadaptations in stress-related neural and neuroendocrine pathways and high craving that predicted heavy drinking and relapse outcomes. Current preliminary data indicates that AUD patients with CP (AUD+/CP+) and also AUD-/CP+ drinkers report higher cue-induced craving and greater heavy drinking days (HDD), along with specific pain-related insula dysregulation that predicts high cue-induced craving and greater HDD. However, the specific alterations in pain-related neural and biobehavioral circuits that promote pain-related heavy drinking is not known. Based on this preliminary data and previous research, we hypothesize that specific alcohol-related insula neuroadaptations promote higher cue-related alcohol craving and greater pain-related HDD, and that reduction in this specific insula dysregulation and in cue-related alcohol craving with effective standard behavioral treatment will improve pain-related alcohol heavy drinking outcomes in those with AUD+ and CP+ non-AUD drinkers. In a 2 X 2 experimental design with a prospective clinical outcomes phase, men and women with AUD, with/without CP, and non-AUD individuals with/without CP will be studied in two related studies utilizing combined multimethod subjective, neuroendocrine, neural MRI assessments and prospective alcohol use outcomes. The following specific aims are proposed: Aim 1: To examine chronic alcohol- and pain- specific subjective (pain, stress, craving), neural and neuroendocrine responses to visual cue blocks (stress/pain, alcohol, neutral) in AUD (+/-) and CP (+/-) groups. Aim 2: To examine whether specific AUD+ and CP+ neuroadaptations in primary and secondary predictors are associated with prospective, real-world daily alcohol craving, pain and alcohol use outcomes. Aim 3: To evaluate changes in primary and secondary predictors with CBT for AUD and for CP, and whether treatment-related neural, endocrine and subjective responses during fMRI predict treatment-related improvements in daily pain, craving and alcohol use outcomes during the 8-week treatment period. Aim 4: To assess the effects of demographic (sex, age, race) and clinical (trauma, psychiatric history) variables on primary and secondary predictors of AUD and CP comorbidity and on drinking outcomes. Exploratory Aim: To explore whole brain pain-specific structural gray matter volume (GMV) and task-based functional connectivity using connectome-based predictive modeling (CPM) at scan 1, and prediction of changes in pain-related structural GMV and drinking connectomes with CBT treatment. Successful completion of the proposed aims will identify chronic alcohol-related pain-specific neural, subjective and neuroendocrine correlates contributing to increased pain-related alcohol use outcomes, that may then be targeted in treatment development to reduce pain-related drinking outcomes to improve AUD risk and recovery.
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