Reduced gray matter volume in limbic and cortical areas is associated with anxiety and depression in alcohol use disorder patients.

Alcohol use disorder (AUD) is a multifactorial disease closely related to neurodevelopment and environmental factors that influence behavior. This study explored the relationships between brain volume and behavior from an Exploratory Structural Equation Modeling (ESEM) based on the Research Domain Criteria. High-resolution magnetic resonance imaging scans were acquired from recent patients with AUD (n = 50) and healthy controls (HC=50). Group differences were assessed by means of voxel-based morphometry (VBM) and regions of interest (ROIs). Participants completed a battery of neurocognitive tasks and emotional tests. When controlling for age, education levels, and total intracranial volume, we found lower gray matter volume in cortical and limbic areas, as well as significant impairments in the AUD group on cognition and affective status. This study demonstrated the importance of multifactorial analysis and complex models in order to better understand substance use disorders. The brain losses may have been the result of neurodevelopmental impairments due to biological and environmental factors that predisposed to AUD or the result of drug abuse. The ESEM indicated that limbic areas indirectly affected the alcohol severity through emotional dysfunction. These results suggest a more relevant involvement of limbic regions for the severity of alcohol use, showing a more significant association between AUD and mood disorders.