Wwhite matter integrity and alcohol use disorders

Injury to the brain's white matter is a signature injury of alcohol use disorders (AUD), yet research on its causes and correlates has yielded mixed findings. This study used structural equation modeling (SEM) to test associations between clinical and demographic factors and variability in white matter integrity in heavy drinkers (mean age = 30.86 +/- 9.08 years; 30% female; 62% treatment-naive). Magnetic resonance imaging scans, including diffusion tensor imaging (DTI), were collected from 324 individuals who reported recent heavy drinking (at least 5 binge-drinking episodes in the past 30 days, or > 14 standard drinks/week for women and > 21 standard drinks/week for men). Drinking history, alcohol problem severity, and cognitive functioning also were assessed. A latent factor representing white matter integrity was created from DTI metrics of 8 white matter regions of interest associated with alcohol cue reactivity in a previous study (Monnig et al., under review). Mediation of the path from duration of drinking to this white matter integrity factor (WMIF) by problem severity and drinking history variables was tested using SEM. Moderated mediation by gender, treatment-seeking status, smoking status, and comorbidity then was tested. Results showed that problem severity and frequency of drinking partially mediated the path from number of years drinking to WMIF, with both mediators contributing to lower WMIF scores. In addition, gender moderated the indirect path through frequency of drinking, with more frequent drinking linked to lower WMIF scores in women but not men. WMIF was significantly, positively associated with visuospatial ability in the entire sample. WMIF partially mediated the path from duration of drinking to visuospatial scores. Treatment-seeking status moderated the effect such that treatment-seeking but not treatment-naive individuals showed a positive association between WMIF scores and visuospatial ability. Finally, an exploratory analysis found preliminary support for the hypothesis that white matter integrity impacts drinking intensity through subjective loss of control over drinking. Investigating the association of heavy drinking with variability in white matter integrity is a novel application of SEM. This study contributes to understanding of how drinking behavior and individual differences relate to integrity of white matter networks implicated in AUD.