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 (GM) volume, as is the normal aging process. Less apparent, however, is how the interaction between aging and heavy alcohol use affects changes in GM across the lifespan. There is some evidence that women are more vulnerable to the negative effects of alcohol use on GM than men. In the current study, we examined whether localized GM 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 GM associations with alcohol use disorder (AUD) severity are moderated by sex and age. Results showed significant negative associations between AUD severity and GM 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 GM volumes were observed as early as 18-25 years. These findings support that alcohol has deleterious effects on global and regional GM above and beyond age, and, of particular importance, that regional associations emerge in early adulthood. Hum Brain Mapp 37:2276-2292, 2016. © 2016 Wiley Periodicals, Inc.

Keywords: aging; alcohol use disorder; neuroimaging; sex differences; surface-based morphometry; voxel-based morphometry.

Figure 1

Clusters of GM volume showing significant negative association with AUDIT in FSL VBM (P < 0.05, z= −20, −10, 0, 10, 20, and 35; random color assignment by cluster).

Figure 2

Clusters of GM volume showing significant negative association with AUDIT score for FreeSurfer SBM (P < 0.05; medial pial surfaces for left hemisphere, lateral pial surfaces for left and right hemispheres, respectively; random color assignment by cluster).

Figure 3

Significant age by AUDIT interaction for FSL VBM volume in the right insula, plotted by age group (18–25, 26–35, and 36–55 years old).

Figure 4

Significant sex by AUDIT interaction for FreeSurfer SBM cortical thickness in the left lateral OFC.