Brain glutathione levels and associations with recent drinking in treatment-naïve individuals with alcohol use disorder versus light drinkers

IF 3.9 2区医学 Q1 PSYCHIATRY

Drug and alcohol dependence Pub Date : 2025-05-08 DOI:10.1016/j.drugalcdep.2025.112705

James J. Prisciandaro , Joseph P. Schacht , Andrew P. Prescot , Raymond F. Anton

{"title":"Brain glutathione levels and associations with recent drinking in treatment-naïve individuals with alcohol use disorder versus light drinkers","authors":"James J. Prisciandaro , Joseph P. Schacht , Andrew P. Prescot , Raymond F. Anton","doi":"10.1016/j.drugalcdep.2025.112705","DOIUrl":null,"url":null,"abstract":"<div><h3>Background and aims</h3><div>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.</div></div><div><h3>Design setting and participants</h3><div>Secondary analyses were conducted on cross-sectional neuroimaging data from (<em>n</em> = 20) treatment-naïve individuals with AUD and (<em>n</em> = 20) demographically matched LD participants at a medical university in South Carolina, USA.</div></div><div><h3>Measurements</h3><div>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.</div></div><div><h3>Findings</h3><div>Significantly higher dACC GSH/water levels were observed in AUD participants (<em>M</em> = 0.88, <em>SD</em> = 0.16) than in LD participants (<em>M</em> = 0.70, <em>SD</em> = 0.16, <em>F</em> = 12.00, <em>p</em> < 0.001; Cohen’s <em>d</em> = 1.10). A<em>d</em>ditionally, there was a significant interaction between GSH/water levels and participant group (<em>F</em> = 5.71, <em>p</em> = 0.022), such that higher GSH/water levels were associated with lower nHDD in AUD (<em>r</em> = -0.46, <em>p</em> = 0.040) but not LD (<em>r</em> = 0.24, <em>p</em> = 0.329) <em>p</em>articipants.</div></div><div><h3>Conclusions</h3><div>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.</div></div>","PeriodicalId":11322,"journal":{"name":"Drug and alcohol dependence","volume":"272 ","pages":"Article 112705"},"PeriodicalIF":3.9000,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Drug and alcohol dependence","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0376871625001589","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"PSYCHIATRY","Score":null,"Total":0}

引用次数: 0

Abstract

Background and aims

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.

Design setting and 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.

Measurements

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.

Findings

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.

Conclusions

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.

查看原文本刊更多论文

脑谷胱甘肽水平及其与近期饮酒treatment-naïve酒精使用障碍个体与轻度饮酒者的关系

背景和目的反复接触乙醇会产生过度的氧化应激，导致细胞损伤，而谷胱甘肽（GSH），大脑的主要抗氧化剂，赋予了关键的第一道防线。本研究旨在比较treatment-naïve酒精使用障碍（AUD）个体和轻度饮酒对照组（LD）参与者的脑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的关系。设计环境和参与者对美国南卡罗来纳州一所医科大学（n = 20） treatment-naïve AUD患者和（n = 20） LD患者的横断面神经影像学数据进行了二次分析。测量：通过质子磁共振光谱获得背前扣带皮层（dACC）的scsf校正和水参考谷胱甘肽水平，通过时间线随访访谈获得过去14天的重度饮酒天数（nHDD）。AUD参与者的dACC GSH/水水平（M = 0.88, SD = 0.16）显著高于LD参与者(M = 0.70, SD = 0.16, F = 12.00, p < 0.001；Cohen’s d = 1.10)。此外，GSH/水水平与参与者组之间存在显著的相互作用（F = 5.71, p = 0.022），因此，在AUD （r = -0.46, p = 0.040）中，较高的GSH/水水平与较低的nHDD相关（r = 0.24, p = 0.329），但与LD （r = 0.24, p = 0.329）参与者无关。结论：这项初步研究的结果与treatment-naïve AUD患者对中度氧化应激的代偿性谷胱甘肽上调的解释一致，为酒精相关细胞损伤的氧化应激模型提供了独特的支持，并强调了抗氧化治疗AUD的潜在前景。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Drug and alcohol dependence 医学-精神病学

CiteScore

7.40

自引率

7.10%

发文量

409

审稿时长

41 days

期刊介绍： Drug and Alcohol Dependence is an international journal devoted to publishing original research, scholarly reviews, commentaries, and policy analyses in the area of drug, alcohol and tobacco use and dependence. Articles range from studies of the chemistry of substances of abuse, their actions at molecular and cellular sites, in vitro and in vivo investigations of their biochemical, pharmacological and behavioural actions, laboratory-based and clinical research in humans, substance abuse treatment and prevention research, and studies employing methods from epidemiology, sociology, and economics.