Autoantibodies and Inflammation in Schizophrenia
Hiroki Shiwaku
Abstract
The potential role of autoantibodies in the etiology of schizophrenia is a key research focus because growing evidence suggests an association between immune dysfunction and psychotic disorders. This hypothesis is supported by findings indicating immune-related abnormalities in patients with schizophrenia, including chronic inflammation and genetic alterations associated with immune system dysregulation. Epidemiological studies have reinforced this perspective by demonstrating a significant correlation between autoimmune diseases and schizophrenia, suggesting shared pathological mechanisms including autoantibodies. A particularly compelling line of evidence comes from the identification of autoantibodies targeting synaptic molecules in patients with schizophrenia. Autoantibodies against N-methyl-D-aspartate (NMDA) receptors, gamma-aminobutyric acid (GABA) receptors, neural cell adhesion molecule 1 (NCAM1), and neurexin 1 (NRXN1) have been detected in patients, raising the possibility that immune-mediated synaptic dysfunction contributes to the disorder's pathophysiology. Experimental studies support this notion because the administration of these autoantibodies in mice induces molecular, cellular, and behavioral abnormalities that mirror aspects of schizophrenia. This review summarizes the relationships among schizophrenia, inflammation, immune-related genetic factors, autoimmune diseases, and autoantibodies. Furthermore, this review discusses future research directions for further elucidating the role of autoantibodies in schizophrenia.