Differing effects of alcohol use on epigenetic and brain age in adult children of alcoholic parents

It is known that being the adult child of an alcoholic (ACoA) can confer a wide variety of increased health and psychological risks, including higher rates of anxiety, depression, and posttraumatic stress disorder symptoms. Additionally, ACoAs are at greater risk of developing substance use disorders than individuals from non-alcoholic families. To better understand the psychobiological factors underlying these risks, ACoA individuals with risky hazardous alcohol use (n=14) and those not engaged in hazardous use (n=14) were compared to a group of healthy controls. We examined structural brain differences and applied machine learning algorithms to predict biological brain and DNA methylation ages to investigate differences between these groups. Contrary to our hypothesis, we found that hazardous and non-hazardous ACoA groups had lower predicted brain ages than the healthy control group (n=100), which may result from neuro-developmental differences between ACoA groups and controls. When examining specific brain regions, we observed decreased cortical volume within bilateral pars orbitalis and frontal poles, as well as the left middle temporal gyrus and entorhinal cortex within the hazardous alcohol ACoA group, all areas consistent with previous research examining how alcohol use affects brain structure. When looking at the epigenetic aging data, the hazardous ACoA participants had increased predicted epigenetic age difference scores compared to the control group (n=34) and the non-hazardous ACoA participant groups. In summary, the results demonstrate a decreased brain age in the ACoAs compared to control, concurrent with increased epigenetic age specifically in the hazardous ACoA group, laying the foundation for future research to identify individuals that may have an increased susceptibility to developing hazardous alcohol use. Together, these results provide a better understanding of the associations between epigenetic factors, brain structure, and alcohol use disorders. ### Competing Interest Statement The authors have declared no competing interest.