Genes and Brain Structure in Alcohol Use Disorder

Newswise — Alcohol use disorder (AUD) is a common addictive disease that affects the brain. The risk of developing AUD is due, nearly equally, to environmental and genetic effects.  More than 3,000 genes have been linked to AUD or the response to alcohol. Brain imaging studies have revealed alterations in brain structure and function related to AUD.  However, few studies have linked genes to brain findings in individuals with an AUD diagnosis.

Researchers used magnetic resonance imaging (MRI) to examine the insular cortex, a brain region that plays a critical role in brain processes including cognition, perception, motor control, self-consciousness, and emotional regulation. The insula also has been implicated in AUD, drug addiction, and craving, as well as the response to alcohol-related cues. In this study, DNA methylation, which is the addition of a methyl group to DNA that is part ofepigenetic reprogramming of genes, a key means by which the body regulates gene expression, was examined in the insula of 52 individuals with AUD and 58 healthy comparison subjects. 

Results showed that the AUD group had a significantly larger insular surface area than the comparison group, in both the left and right hemispheres of the brain. Forty-fourof the DNA methylation probes associated with the right insula were significantly correlated with AUD status.  Nearly half of the protein-coding genes represented by these probes were previously associated with AUD or the response to alcohol, but 20 new genes were also identified.

This study is novel in that it used brain imaging to guide the study of epigenetic mechanisms involved in AUD. The insula, the region of interest here, may help to adjust the reward value of a stimulus, such as alcohol, to help satisfy an individual’s internal and external environmental needs. The integration of large-scale, high-dimensional brain imaging and genetic data targeting the insula and DNA methylation may advance our understanding of the neurobiological vulnerability to AUD and help measure the response to AUD treatment.