Alcohol use disorder-associated structural and functional characteristics of the insula.

Based on our current understanding of insular regions, effects of chronic alcohol use on the insula may affect the integration of sensory-motor, socio-emotional, and cognitive function. There is no comprehensive understanding about these differences in individuals with alcohol use disorder that accounts for both structural and functional differences related to chronic alcohol use. The purpose of this study was to investigate these variations in both the anterior and posterior insula in persons with alcohol use disorder. We investigated insula gray matter volume, morphometry, white matter structural connectivity, and resting state functional connectivity in 75 participants with alcohol use disorder (females = 27) and 75 age-matched healthy control participants (females = 39). Results indicated structural differences mostly in the anterior regions, while functional connectivity differences were observed in both the anterior and posterior insula in those with alcohol use disorder. Differing connectivity was observed with frontal, parietal, occipital, cingulate, cerebellar, and temporal brain regions. While these results align with prior studies showing differences primarily in anterior insular regions, they also contribute to the existing literature suggesting differences in anterior insular connectivity with brain regions shown to be engaged during higher cognitive and emotional tasks.

Severity of alcohol use disorder influences sex differences in sleep, mood, and brain functional connectivity impairments.

Growing evidence suggests greater vulnerability of women than men to the adverse effects of alcohol on mood and sleep. However, the underlying neurobiological mechanisms are still poorly understood. Here, we examined sex difference in resting state functional connectivity in alcohol use disorder using a whole-brain data driven approach and tested for relationships with mood and self-reported sleep. To examine whether sex effects vary by severity of alcohol use disorder, we studied two cohorts: non-treatment seeking n = 141 participants with alcohol use disorder (low severity; 58 females) from the Human Connectome project and recently detoxified n = 102 treatment seeking participants with alcohol use disorder (high severity; 34 females) at the National Institute on Alcohol Abuse and Alcoholism. For both cohorts, participants with alcohol use disorder had greater sleep and mood problems than healthy control, whereas sex by alcohol use effect varied by severity. Non-treatment seeking females with alcohol use disorder showed significant greater impairments in sleep but not mood compared to non-treatment seeking males with alcohol use disorder, whereas treatment-seeking females with alcohol use disorder reported greater negative mood but not sleep than treatment-seeking males with alcohol use disorder. Greater sleep problems in non-treatment seeking females with alcohol use disorder were associated with lower cerebello-parahippocampal functional connectivity, while greater mood problems in treatment-seeking females with alcohol use disorder were associated with lower fronto-occipital functional connectivity during rest. The current study suggests that changes in resting state functional connectivity may account for sleep and mood impairments in females with alcohol use disorder. The effect of severity on sex differences might reflect neuroadaptive processes with progression of alcohol use disorder and needs to be tested with longitudinal data in the future.