Targeting Neuroinflammation in Schizophrenia: A comprehensive review of mechanisms and pharmacological interventions

Int Immunopharmacol. 2025 May 26;159:114910. doi: 10.1016/j.intimp.2025.114910. Online ahead of print.

ABSTRACT

Schizophrenia is a complex psychiatric disorder traditionally linked to neurotransmitter imbalances, but growing evidence implicates neuroinflammation as a key factor in its pathogenesis. Core pathological features include aberrant microglial activation, elevated proinflammatory cytokines (e.g., IL-6, TNF-α), blood-brain barrier disruption, and oxidative stress, all contributing to neuronal dysfunction. Genetic, epigenetic, and neurodevelopmental abnormalities further intensify the link between neuroinflammation and clinical symptoms, including cognitive deficits and positive/negative symptoms. Therapeutically, anti-inflammatory strategies show promise: Non-steroidal anti-inflammatory drugs inhibit the cyclooxygenase pathway; minocycline modulates microglial activity; cytokine inhibitors regulate immune responses; and antioxidants and mitochondrial agents (e.g., N-acetylcysteine, omega-3 fatty acids) reduce oxidative damage. Emerging approaches such as cannabidiol and nanodelivery systems also demonstrate anti-inflammatory and neuroprotective potential. However, long-term safety, dosage optimization, and individual variability remain to be fully validated. Future research should integrate single-cell genomics, neuroimaging, and biomarker stratification to elucidate neuroinflammatory mechanisms and enable precise combination therapies. Combining immunomodulatory and neurotransmitter-based strategies may overcome the limitations of traditional antipsychotics and improve clinical outcomes.

PMID:40424655 | DOI:10.1016/j.intimp.2025.114910