Redox Homeostasis and Oxidative Stress in Schizophrenia: Glutathione–NMDA–Neuroimmune Convergence and a Hypothesis-Generating Iron–Lipid Redox Extension

Schizophrenia is a heterogeneous neurodevelopmental disorder in which genetic liability, developmental exposures, illness stage, treatment, and metabolic or inflammatory comorbidity may shape redox biology. This narrative review evaluates the human and mechanistic evidence for impaired redox adaptation as a convergence mechanism linking glutathione (GSH) regulation, N-methyl-D-aspartate receptor hypofunction, parvalbumin-interneuron and perineuronal-net vulnerability, mitochondrial–glial dysfunction, and neuroimmune signalling. The findings do not support a uniform oxidative abnormality across all patients or compartments: the peripheral biomarkers are heterogeneous, the group-level brain GSH magnetic resonance spectroscopy findings are largely null, and treatment-related changes vary by marker and illness phase. Beyond the established GSH–NMDA–redox–immune models, we integrate iron–lipid redox regulation as a conditional, hypothesis-generating extension and apply a deliberately conservative evidence hierarchy. Human studies more often report a lower peripheral iron and reduced or redistributed brain iron than a uniform iron excess; the plasma signals for predominantly intracellular proteins remain analytically unvalidated, and ferroptotic neuronal death has not been demonstrated. Longitudinal, sex-aware, multi-compartment, and challenge-based studies are needed to define meaningful redox subgroups; no redox- or ferroptosis-related biomarker is currently validated to guide treatment selection.