ORIGINAL RESEARCH article
Front. Psychiatry
Sec. Addictive Disorders
Volume 16 - 2025 | doi: 10.3389/fpsyt.2025.1560053
The effects of alcohol use severity and polygenic risk on gray matter volumes in young adults
Provisionally accepted
- 1School of Medicine, Yale University, New Haven, United States
- 2Yale College, Yale University, New Haven, Connecticut, United States
- 3Beijing University of Technology, Beijing, Beijing Municipality, China
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Genetic factors contribute to alcohol misuse. Chronic alcohol consumption is associated with decreases in gray matter volumes (GMVs) of the brain. However, it remains unclear whether or how genetic risks may alter GMVs independent of the effects of alcohol exposure. Here, we employed the Human Connectome Project data of neurotypical adults (n = 995; age 22-35; 618 women) and, with voxel-based morphometry analysis, computed the GMVs of 166 regions in the automated anatomical atlas 3. Alcohol use behaviors were assessed with the Semi-Structured Assessment for the Genetics of Alcoholism. Alcohol use severity was quantified by the first principal component (PC1) identified of principal component analysis of 15 drinking measures.Polygenic risk scores (PRS) for alcohol dependence were computed for all subjects using the Psychiatric Genomics Consortium study of alcohol dependence as the base sample. With age, sex, race, and total intracranial volume as covariates, we evaluated the relationships of regional GMVs with PC1 and PRS together in a linear regression.PC1 was negatively correlated with GMVs of right insula and Heschl's gyrus, and PRS was positively correlated with GMVs of left posterior orbitofrontal cortex, bilateral intralaminar nuclei of the thalamus and lingual gyri. These findings suggest distinct volumetric neural markers of drinking severity and genetic risks of alcohol misuse.Notably, in contrast to volumetric reduction, the genetic risks of dependent drinking may involve larger regional volumes in the reward, emotion, and saliency circuits.
Keywords: Hcp, alcohol dependence, PRs, VBM, Thalamus
Received: 13 Jan 2025; Accepted: 21 Apr 2025.
Copyright: © 2025 Chen, Li, Luo, Li, Ide and Li. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Yu Chen, School of Medicine, Yale University, New Haven, United States
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