The role of infections and inflammation in schizophrenia: review of the evidence

Abstract

Schizophrenia is a severe mental illness affecting approximately 1% of the population worldwide. While its exact causes remain unknown, emerging evidence suggests that infections and inflammation may contribute to disease development in a subset of individuals. This review comprehensively summarizes the evidence linking infections, immune system dysfunction, and schizophrenia risk. Several population-based studies have linked serious prenatal or childhood infections requiring hospitalization to increased risk of later schizophrenia diagnosis, especially in individuals with genetic predisposition. Both central nervous system infections and systemic infections appear to confer risk. Specific pathogens including Toxoplasma gondii, herpesviruses, Chlamydophila, and more have been implicated. Autoimmune diseases are also associated with increased schizophrenia susceptibility, possibly due to blood-brain barrier disruption allowing brain-reactive antibodies access. The recent Coronavirus disease 2019 (COVID-19) pandemic raises questions about SARS-CoV-2 as a risk factor for new-onset psychosis. The mechanisms underlying the infection-schizophrenia link likely involve inflammation, cytokines, microglial activation, and tryptophan/kynurenine pathway modulation. Treatments targeting inflammation showed some efficacy in schizophrenia, further supporting an inflammation hypothesis. While the epidemiological and mechanistic evidence is substantial, further research is needed to conclusively determine the exact mechanisms linking immune dysfunction to schizophrenia requires further study. The evidence suggests immune system abnormalities likely play a role, perhaps by interacting with genetic and environmental factors, in instigating schizophrenia pathophysiology in a subset of patients. More research is needed to understand these connections more clearly which may aid future prevention and personalized treatment approaches tailored to specific illness subtypes.