Persistent oxidative stress and functional outcomes in early psychosis: A longitudinal study

To evaluate total oxidative capacity (TOC), total antioxidative capacity (TAC), and 4‑hydroxy-2-nonenal (4-HNE) levels in patients with acute psychosis and after three months of treatment, and examine their associations with psychopathological and functional outcomes.

A prospective cohort included 122 male patients with psychotic disorders (International Classification of Diseases, 10th Revision: ICD-10, F20-F29) and 102 healthy controls. Clinical status was assessed using the Positive and Negative Syndrome Scale (PANSS), Scale for the Assessment of Negative Symptoms (SANS), Global Assessment of Functioning (GAF), Functional Remission of General Schizophrenia Scale (FROGS), and the 5-item Quality of Life Scale (QLS-5).

Compared with the controls, the patients had higher TOC and 4-HNE levels and lower TAC levels. The largest effect was observed for TAC (Cliff's δ = -0.55; 95 % CI, -0.66 to -0.41). Lower TAC was correlated with more severe negative symptoms, particularly avolition/apathy (τb = 0.18; p = 0.008) and anhedonia/asociality (τb = 0.17; p = 0.009). Despite substantial clinical improvement, oxidative stress markers remained unchanged after treatment. After three months, PANSS total scores decreased by 64 % (Hedges' g = -2.95), while quality of life improved by 37 % (Hedges' g = 1.12). Symptomatic remission was achieved in 88.5 % of the patients.

The findings indicate a persistent oxidative imbalance in early psychosis, suggesting redox dysregulation as a stable, trait-like substrate rather than a state-dependent phenomenon. Oxidative biomarkers may be useful for clarifying disease mechanisms and monitoring the functional outcomes. Therapeutic approaches targeting redox processes may complement current psychosis treatments.