1University of Colorado at Boulder
Recent studies have suggested that perturbation of the immune system is a critical mechanism in the etiology of AUDs. More specifically, alcohol produces deleterious effects on peripheral and central immune signaling pathways, particularly through activation of lipopolysaccharide (LPS)-induced TLR4 signaling cascades that span the gut, liver, and brain, and coincide with the release of cytokines and activation of pro-inflammatory pathways in the brain. In turn, repeated activation of pro-inflammatory pathways and microglia is associated with neural damage, especially in brain regions involved in executive function and control. Concurrently, epigenetic regulation of genes involved in alcohol reward may alter reward networks in the brain. The presentation will focus on the role of epigenetic regulation of genes involved in inflammatory response (e.g., TLR4 and CYP2E1) as well as genes implicated in the rewarding effects of alcohol (e.g., DRD2). Results indicate that TLR4 methylation is associated with deleterious changes in gray matter density and white matter integrity (p < .05), while changes in DRD2 methylation is associated with changes in BOLD response to alcohol cues and changes in functional connectivity. Overall, these studies are beginning to elucidate the mechanisms that may underlie the effects of alcohol on brain networks related to loss of control. These studies suggest that interventions targeting inflammation may have an important role in the treatment of AUDs.