Negative and interactive effects of sex, aging, and alcohol abuse on gray matter morphometry

Abstract

Chronic alcohol use is associated with declines in gray matter volume, as is the normal aging process. Less apparent, however, is how the interaction between aging and heavy alcohol use affects changes in gray matter across the lifespan. There is some evidence that women are more vulnerable to the negative effects of alcohol use on gray matter than men. In the current study, we examined whether localized gray matter was related to measures of alcohol use disorder (e.g., AUDIT score) in a large sample (N = 436) of participants, ages 18–55 years, with a range of disease severity, using both voxel-based morphometry (VBM) and surface-based morphometry (SBM). We also explored whether gray matter associations with alcohol use disorder (AUD) severity are moderated by sex and age. Results showed significant negative associations between AUD severity and gray matter volume throughout temporal, parietal, frontal, and occipital lobes. Women showed more negative effects of alcohol use than men for cortical thickness in left orbitofrontal cortex, but evidence for increased vulnerability based on sex was limited overall. Similarly, a specific age by alcohol use interaction was observed for volume of right insula, but other regional or global interactions were not statistically supported. However, significant negative associations between heavy alcohol use and gray matter volumes were observed as early as 18–25 years. These findings support that alcohol has deleterious effects on global and regional gray matter above and beyond age, and, of particular importance, that regional associations emerge in early adulthood.

Structural neuroimaging correlates of alcohol and cannabis use in adolescents and adults

“…Our previous results suggested widespread negative associations of medium effect size between alcohol use and GM throughout the brain and cerebellum, above and beyond important confounding variables such as age. Negative associations between alcohol use and GM volume were observed even among the youngest age group of the sample (ages 18 to 25 years) [8]. The current study supported previous VBM results among adults, such that large clusters of negative association between problem drinking and GM volume (e.g., accounting for approximately 15% of variance) were observed.…”

“…Chronic alcohol consumption is associated with lower gray matter (GM) volume globally [3–5] and in specific cortical structures [6–7]. Results of our recent large-scale study support a negative correlation between alcohol use severity and global GM volume in adults as young as 18 years [8]. Studies among adolescents suggest regional reductions in frontal [9–11], temporal and parietal [10], and cerebellar volume [12], or differences localized to specific structures such as the hippocampus [13].…”

“…The current study sought to expand previous work on associations between alcohol use and GM structure [8] by further examining WM microstructure; and by examining these associations among adults and adolescents. Given the inconclusive prior evidence regarding the possible relationship between cannabis use and brain structure [26], we also tested associations between structural measures and recent cannabis use.…”

“…Data for adolescents were pooled from two existing neuroimaging studies among high-risk adolescents who were recruited to participate in a sexual health intervention [44–46]. Importantly, subsamples within the pooled dataset have been reported upon previously [8, 42], and were included here to maximize sample sizes and include a wide range of substance use. Key predictors of alcohol and cannabis use were treated as continuous measures, and participants with a wide range of use were included to test strengths of associations in GLM.…”

“…We examined general linear models (GLM) in GM and WM that included terms for alcohol and cannabis use, with follow up cannabis models comprising participants reporting weekly or greater cannabis use. Based on our previous work [8], we hypothesized that negative associations between alcohol use and GM would be observed in adults throughout frontal and parietal regions and cerebellum, and similar but less widespread associations would be observed in adolescents. We also expected that alcohol use would show widespread negative association with WM integrity among adults, and to a lesser extent among adolescents.…”