Role of inflammation in the pathogenesis of schizophrenia: A review of the evidence, proposed mechanisms and implications for treatment

• Published in: Early intervention in psychiatry Vol. 14; no. 4; pp. 385 - 397
• Main Authors: Mongan, David, Ramesar, Matthew, Föcking, Melanie, Cannon, Mary, Cotter, David
• Format: Journal Article
• Language: English
• Published: Melbourne Wiley Publishing Asia Pty Ltd 01.08.2020; Wiley Subscription Services, Inc
• Subjects: aetiology; Animals; Anti-Inflammatory Agents - therapeutic use; Biomarkers; Cytokines; Humans; immune system; Immunomodulation; Immunomodulators; Inflammation; Inflammation - drug therapy; Inflammation - immunology; Literature reviews; Pathogenesis; Schizophrenia; Schizophrenia - drug therapy; Schizophrenia - immunology; treatment; aetiology; immune system; treatment; schizophrenia; inflammation
• ISSN: 1751-7885; 1751-7893; 1751-7893
• DOI: 10.1111/eip.12859

Aim Over the past several decades, there has been a growing research interest in the role of inflammation in the pathogenesis of schizophrenia. This review aims to summarize evidence in support of this relationship, to discuss biological mechanisms that might explain it, and to explore the translational impact by examining evidence from trials of anti‐inflammatory and immunomodulatory agents in the treatment of schizophrenia. Methods This narrative review of the literature summarizes evidence from observational studies, clinical trials and meta‐analyses to evaluate the role of inflammation in the pathogenesis of schizophrenia and to discuss associated implications for treatment. Results Epidemiological evidence and animal models support a hypothesis of maternal immune activation during pregnancy, which increases the risk of schizophrenia in the offspring. Several biomarker studies have found associations between classical pro‐inflammatory cytokines and schizophrenia. The precise biological mechanisms by which inflammatory processes might contribute to the pathogenesis of schizophrenia remain unclear, but likely include the actions of microglia and the complement system. Importantly, several trials provide evidence that certain anti‐inflammatory and immunomodulatory agents show beneficial effects in the treatment of schizophrenia. Nevertheless, there is a need for further precision‐focused basic science and translational research. Conclusions Increasing our understanding of the role of inflammation in schizophrenia will enable novel opportunities for therapeutic and preventative interventions that are informed by the underlying pathogenesis of this complex disorder.