Glutathione as a molecular marker of functional impairment in patients with at-risk mental state: 7-Tesla ¹H-MRS study

Abstract

A substantial number of individuals with clinical high-risk (CHR) mental state do not transition to psychosis. However, regardless of future diagnostic trajectories, many of these individuals develop poor social and occupational functional outcomes. The levels of glutathione, a crucial cortical antioxidant, may track variations in functional outcomes in early psychosis and prodromal states.Thirteen clinical high-risk and 30 healthy control volunteers were recruited for a 7-Tesla magnetic resonance spectroscopy scan with voxel positioned within the dorsal anterior cingulate cortex (ACC). Clinical assessment scores were collected to determine if any association was observable with glutathione levels.Bayesian Spearman test revealed a positive association between the Social and Occupational Functioning Assessment Scale (SOFAS) and the glutathione concentration in the clinical high-risk group but not in the healthy control group. After accounting for variations in SOFAS, CHR group had higher GSH levels than the healthy subjects.This study is the first to use 7-Tesla magnetic resonance spectroscopy to test whether ACC glutathione levels related to social and occupational functioning in a clinically high-risk group and offers preliminary support for glutathione levels as a clinically actionable marker of prognosis in emerging adults presenting with risk features for various severe mental illnesses.

Ultra-high field neuroimaging in psychosis: A narrative review

“…Limongi et al (36) proposed that higher glutathione levels could reverse the glutamate-mediated dysconnectivity based on resting-state functional MRI-based causal modeling in combination with 7T MRS. In line with this, youth who are at a high risk for psychosis have higher glutathione in association with superior social functioning (37,38).…”

Central oxidative stress and early vocational outcomes in first episode psychosis: A 7-Tesla Magnetic Resonance Spectroscopy study of glutathione

“…While peripheral markers of oxidative stress correlate with concentration of the primary intracortical antioxidant glutathione 14 levels in first episode psychosis; in a sub-sample from this study, treatment related increase in GSH was associated with a gain in global functioning scores 16 . In a small group of individuals with various mental health difficulties indicating a high-risk state for psychosis, we recently demonstrated higher GSH levels measured using magnetic resonance spectroscopy (MRS) from the dorsal anterior cingulate cortex (ACC) in those with better social and occupational functioning 17 . In the current study, we investigate if ACC GSH levels measured at the onset of psychosis, before establishing regular antipsychotic treatment, predict later functional outcomes in the first year of early intervention.…”