Prisciandaro James J, Schacht Joseph P, Prescot Andrew P, Anton Raymond F
Department of Psychiatry and Behavioral Sciences, Medical University of South Carolina, United States.
Department of Psychiatry, University of Colorado Anschutz Medical Campus, United States.
Drug Alcohol Depend. 2025 Jul 1;272:112705. doi: 10.1016/j.drugalcdep.2025.112705. Epub 2025 May 12.
Repeated ethanol exposure produces excess oxidative stress resulting in cellular damage, with glutathione (GSH), the brain's primary antioxidant, conferring a critical first line of defense. This study aimed to compare brain GSH levels between treatment-naïve individuals with Alcohol Use Disorder (AUD) and light drinking control participants (LD). This study also aimed to evaluate associations of brain GSH levels with recent heavy drinking in AUD and LD participants.
Secondary analyses were conducted on cross-sectional neuroimaging data from (n = 20) treatment-naïve individuals with AUD and (n = 20) demographically matched LD participants at a medical university in South Carolina, USA.
CSF-corrected and water-referenced GSH levels from dorsal anterior cingulate cortex (dACC) acquired via proton MR spectroscopy and past 14-day number of heavy drinking days (nHDD) acquired via Time-Line Followback interview.
Significantly higher dACC GSH/water levels were observed in AUD participants (M = 0.88, SD = 0.16) than in LD participants (M = 0.70, SD = 0.16, F = 12.00, p < 0.001; Cohen's d = 1.10). Additionally, there was a significant interaction between GSH/water levels and participant group (F = 5.71, p = 0.022), such that higher GSH/water levels were associated with lower nHDD in AUD (r = -0.46, p = 0.040) but not LD (r = 0.24, p = 0.329) participants.
The findings from this preliminary study are consistent with an interpretation of compensatory GSH upregulation in response to moderate oxidative stress in treatment-naïve individuals with AUD, adding unique support to oxidative stress models of alcohol-related cellular damage and highlighting the potential promise of antioxidant treatments for AUD.
反复接触乙醇会产生过量氧化应激，导致细胞损伤，而谷胱甘肽（GSH）作为大脑主要抗氧化剂，构成关键的第一道防线。本研究旨在比较初次接受治疗的酒精使用障碍（AUD）患者与轻度饮酒对照参与者（LD）之间的脑GSH水平。本研究还旨在评估AUD和LD参与者脑GSH水平与近期大量饮酒之间的关联。
设计、地点与参与者：对来自美国南卡罗来纳州一所医科大学的（n = 20）初次接受治疗的AUD患者和（n = 20）人口统计学匹配的LD参与者的横断面神经影像数据进行二次分析。
通过质子磁共振波谱法获取背侧前扣带回皮质（dACC）经脑脊液校正和以水为参照的GSH水平，以及通过时间线随访访谈获取过去14天的大量饮酒天数（nHDD）。
AUD参与者（M = 0.88，标准差 = 0.16）的dACC中GSH/水水平显著高于LD参与者（M = 0.70，标准差 = 0.16，F = 12.00，p < 0.001；科恩d值 = 1.10）。此外，GSH/水水平与参与者组之间存在显著交互作用（F = 5.71，p = 0.022），即较高的GSH/水水平与AUD参与者较低的nHDD相关（r = -0.46，p = 0.040），但与LD参与者无关（r = 0.24，p = 0.329）。
这项初步研究结果与如下解释一致：初次接受治疗的AUD患者因中度氧化应激而出现代偿性GSH上调，为酒精相关细胞损伤的氧化应激模型提供了独特支持，并突出了抗氧化治疗对AUD的潜在前景。
