Aguilar L S, Wallace A L, Courtney K E, Wade N E
Department of Psychiatry, University of California, San Diego, USA.
Department of Psychiatry, University of California, San Diego, USA.
Alcohol. 2025 Nov;128:43-50. doi: 10.1016/j.alcohol.2025.08.002. Epub 2025 Aug 20.
Adolescence marks a critical window wherein individual differences in brain structure may influence the emergence of alcohol use behaviors. The orbitofrontal cortex (OFC), a region involved in reward processing and behavioral regulation, may play a key role in shaping early responses to alcohol. This study examined whether smaller OFC volume at ages 9-10 predicted likelihood of experiencing subjective effects of alcohol by ages 13-14. Participants (N = 206; 57 % female) were drawn from the Adolescent Brain Cognitive Development Study. Baseline medial and lateral OFC volumes were used. Subjective response to alcohol was measured during follow-up using a binary outcome (1 = any effect, 0 = no effects). Mixed-effects logistic regression models tested the association between OFC and alcohol response, adjusting for sex, parental education, race/ethnicity, intracranial volume, and site. Smaller left medial OFC at Baseline was significantly associated with greater odds of reporting subjective effects (OR = 1.70, p = .026). Youth who reported subjective effects also consumed more alcohol in the past year (p < .001), but did not differ in their alcohol expectancies. Among those reporting subjective effects, OFC volume was not significantly associated with the amount or frequency of alcohol use. These findings suggest that smaller OFC volume may not reflect pharmacological sensitivity per se, but instead relate to early drinking behavior sufficient to elicit noticeable effects. This may reflect underlying impulsivity-related traits or altered neurodevelopmental trajectories that predispose youth to early and potentially riskier patterns of alcohol use. Results underscore the potential value of identifying structural brain markers that contribute to individual vulnerability for alcohol use during adolescence.
青春期是一个关键时期，在此期间大脑结构的个体差异可能会影响饮酒行为的出现。眶额皮质（OFC）是一个参与奖励处理和行为调节的区域，可能在塑造对酒精的早期反应中起关键作用。本研究调查了9至10岁时较小的眶额皮质体积是否能预测13至14岁时体验酒精主观效应的可能性。参与者（N = 206；57%为女性）来自青少年大脑认知发展研究。使用基线时的内侧和外侧眶额皮质体积。在随访期间使用二元结果（1 = 有任何效应，0 = 无效应）来测量对酒精的主观反应。混合效应逻辑回归模型测试了眶额皮质与酒精反应之间的关联，并对性别、父母教育程度、种族/族裔、颅内体积和研究地点进行了调整。基线时左侧内侧眶额皮质较小与报告主观效应的几率显著增加相关（OR = 1.70，p = .026）。报告有主观效应的青少年在过去一年中饮酒量也更多（p < .001），但他们对酒精的预期没有差异。在报告有主观效应的人群中，眶额皮质体积与饮酒量或饮酒频率没有显著关联。这些发现表明，较小的眶额皮质体积本身可能并不反映药理敏感性，而是与足以引发明显效应的早期饮酒行为有关。这可能反映了潜在的与冲动性相关的特质或神经发育轨迹的改变，使青少年易患早期且可能更具风险的饮酒模式。研究结果强调了识别有助于青少年酒精使用个体易感性的大脑结构标志物的潜在价值。
