Role of Infection, Autoimmunity, Atopic Disorders, and the Immune System in Schizophrenia: Evidence from Epidemiological and Genetic Studies.

An immunologic component to schizophrenia has been increasingly recognized, where infections and chronic inflammatory diseases as atopic disorders and autoimmune diseases could be involved in the pathogenesis of schizophrenia. Psychotic symptoms can be directly triggered by infections reaching the CNS, or be secondary to systemic inflammation indirectly affecting the brain through immune components, such as brain-reactive antibodies and cytokines. Large-scale epidemiological studies have consistently displayed that infections, autoimmune diseases, and atopic disorders are associated with increased risk of schizophrenia and that schizophrenia is associated with increased levels of immune markers at diagnosis. However, since there is also an increased risk of immune-related diseases after the diagnosis with schizophrenia and in family members of individuals with schizophrenia, parts of the association could also be due to heritable factors. Shared genetic factor might account for some of this increased prevalence of immune-related diseases among individuals with schizophrenia, and indeed the most pronounced genetic association with schizophrenia lies within the HLA region, which is one of the most important regions for the immune system. However, genetic studies have shown that the common genetic variants associated with schizophrenia do not seem to increase the susceptibility for acquiring infections. Nonetheless, shared genes with the susceptibility for acquiring infections not captured by the polygenic risk score for schizophrenia could still influence the association.