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

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.