Central Oxidative Stress and Early Vocational Outcomes in First Episode Psychosis: A 7-Tesla Magnetic Resonance Spectroscopy Study of Glutathione

Abstract

Background and hypothesis: Following the first episode of psychosis, some patients develop poor social and occupational outcomes, while others display a pattern of preserved functioning. Evidence from preclinical, genetic, and biochemical studies suggest a role for high oxidative stress in poor functional outcomes among patients. The measurement of intracortical glutathione (GSH) using magnetic resonance spectroscopy (MRS) enables investigating the relationship between central antioxidant tone and functional outcomes at the time of first-episode psychosis (FEP). We hypothesized that patients with higher central antioxidant tone at first presentation will have better functional outcomes in early stages of illness. Study design: We scanned 57 patients with FEP and 30 matched healthy controls and estimated GSH resonance using 7-Tesla MRS. We minimized the confounding effects of illness chronicity, long-term treatment exposure, and metabolic complications by recruiting patients with <2 weeks of lifetime antipsychotic exposure on average and followed up this cohort for the next 1 year to determine functional outcomes. Study results: Patients who achieved employment/education or training status (EET) in the first year, had higher GSH at the baseline than healthy controls. Social and occupational functioning assessment scale (SOFAS) scores were also significantly higher in patients with higher GSH levels at the outset, after adjusting for various confounds including baseline SOFAS. Patients who were not in EET did not differ from healthy subjects in their GSH levels. Conclusion: Our observations support a key role for the central antioxidant tone in the functional outcomes of early psychosis.