Emerging evidence suggests a strong link between inflammation and the pathophysiology of schizophrenia. Activated microglia, elevated pro-inflammatory cytokines, and dysregulation of the kynurenine pathway contribute to glutamatergic and dopaminergic imbalances seen in the disorder. Maternal immune activation, infections, and systemic inflammation—particularly involving interleukin-6 and other cytokines—have been implicated in early brain development and later onset of psychosis. Elevated kynurenic acid levels interfere with neurotransmitter function and may be neurotoxic. Dysregulation of the gut-brain axis and altered microbiota also appear to play a role, compounding neuroinflammatory responses and neurotransmitter disruption.

The anti-inflammatory potential of antipsychotic medications and adjunct therapies has gained attention, with studies showing that agents like celecoxib, minocycline, and N-acetylcysteine may reduce symptom severity by targeting inflammatory pathways. Personalized approaches that integrate immune markers, biomarkers of inflammation, and targeted therapies could improve treatment outcomes—particularly for patients with treatment-resistant schizophrenia, a subgroup that may benefit most from immunomodulatory interventions.

Reference: Nayak U, Manikkath J, Arora D, Mudgal J. Impact of neuroinflammation on brain glutamate and dopamine signalling in schizophrenia: an update. Metab Brain Dis. 2025;40(2):119. doi: 10.1007/s11011-025-01548-3.