Sex-based Influences on White Matter Tract Integrity in Alcohol Use Disorder: a Systematic Review

Women experience worse alcohol-related health consequences compared to men, including greater risk and susceptibility to the neurotoxic effects of alcohol. There is a critical need to identify underlying neurobiological mechanisms underlying sex differences in alcohol use disorder (AUD) phenotypes to better inform individualized treatment options. This report aimed to systematically review existing original literature that examined sex differences in white matter tract integrity in individuals with heavy drinking/AUD using diffusion magnetic resonance imaging (dMRI) and provide recommendations for future research. A systematic review was conducted using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and PubMed and Google Scholar databases from inception until January 1, 2024.

Of 565 studies from the database search, 12 met study criteria. Nine (75%) showed evidence of sex-related differences in white matter tract integrity. Five studies showed greater vulnerability of white matter tract degradation in women with heavy drinking/AUD and four showed greater vulnerability in men with heavy drinking/AUD.

This is the first study to systematically assess the existing literature on sex differences in AUD-related white matter tract integrity. The findings from this systematic review were equivocal. Future research should address the mixed literature by systematically examining sex differences in white matter tract integrity in larger, well-characterized samples to account for confounding factors such as alcohol use history, age, other substance use, and psychiatric comorbidities.