Chen Yu, Li Huey-Ting, Luo Xingguang, Li Guangfei, Ide Jaime S, Li Chiang-Shan R
Department of Psychiatry, Yale University School of Medicine, New Haven, CT, United States.
Yale College, New Haven, CT, United States.
Front Psychiatry. 2025 May 13;16:1560053. doi: 10.3389/fpsyt.2025.1560053. eCollection 2025.
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; ages 22-35; 534 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.
遗传因素导致酒精滥用。长期饮酒与大脑灰质体积（GMV）减少有关。然而，遗传风险是否以及如何独立于酒精暴露的影响而改变GMV仍不清楚。
在此，我们使用了神经典型成年人的人类连接组计划数据（n = 995；年龄22 - 35岁；534名女性），并通过基于体素的形态学分析，计算了自动解剖图谱3中166个区域的GMV。使用酒精中毒遗传学半结构化评估来评估饮酒行为。通过对15项饮酒指标进行主成分分析确定的第一主成分（PC1）来量化饮酒严重程度。以酒精依赖的精神病基因组学联盟研究为基础样本，为所有受试者计算酒精依赖的多基因风险评分（PRS）。以年龄、性别、种族和总颅内体积作为协变量，我们在线性回归中共同评估区域GMV与PC1和PRS之间的关系。
PC1与右侧岛叶和颞横回的GMV呈负相关，PRS与左侧眶额后皮质、双侧丘脑板内核和舌回的GMV呈正相关。
这些发现表明了饮酒严重程度和酒精滥用遗传风险的不同体积神经标志物。值得注意的是，与体积减少相反，依赖饮酒的遗传风险可能涉及奖赏、情感和显著性回路中更大的区域体积。
