Gray matter volume and its molecular profiles characteristic drinking severity in young adults

Alcohol misuse is associated with decreased grey matter volume (GMV) and more rule-breaking behavior. It remains unclear how cortical structures, rule-breaking and alcohol misuse were inter-related. Here, we investigated how GMV are altered in association with the severity of drinking and clinical comorbidities and how men and women differ in this association.

We employed the Human Connectome Project data and included a total of 1053 subjects (484 men) in data analyses. The severity of alcohol use was quantified for individual subjects with the first principal component (PC1) identified from principal component analyses of all drinking measures, quantified by Semi-Structured Assessment for the Genetics of Alcoholism. We performed a whole-brain regression of GMV on drinking PC1 in all subjects and in men and women separately, and evaluated the results at a corrected threshold. We combined the findings and JuSpace toolbox and Gene enrichment to characterize the molecular profiles of GMV features of alcohol use severity.

Higher drinking PC1 was associated with more rule-breaking and lower dorsomedial prefrontal cortex, superior temporal gyrus/posterior insula (STG/pIN) GMV in all subjects, and STG/pIN GMV in men alone. Spatial correlation analyses associated alcohol altered GMV predominantly with dopamine and serotonin signaling in men. Go terms were mainly concentrated in protein binding.

We characterized GMV in link with the severity of alcohol misuse and its comorbidities. These findings extend the literature by elucidating the potential impact of problem drinking on the cortical structures.