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

Following the first episode of psychosis, some patients develop poor social and occupational outcomes, while others display a pattern of preserved functioning. Several lines of evidence from preclinical, genetic and biochemical studies suggest a role for high oxidative stress in poor functional outcomes. The measurement of intracortical glutathione (GSH) using magnetic resonance spectroscopy (MRS) provides an opportunity to investigate the relationship between central antioxidant tone and functional outcomes at the time of first episode psychosis (FEP). A body of epidemiological studies indicates better functional outcomes in patients at early stages of schizophrenia compared to patients at a chronic, established phase of illness. We scanned 57 patients with FEP and 30 matched healthy controls and estimated GSH resonance using 7-Tesla MRS. We minimised 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. Patients with FEP 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 employment, education or training (NEET) did not differ from healthy subjects in their GSH levels. Our observations support a key role for the central antioxidant tone in the functional outcomes of early psychosis.