Immune System Abnormalities in Schizophrenia: An Integrative View and Translational Perspectives

Abstract

The immune system is generally known to be the primary defense mechanism against pathogens. Any pathological conditions are reflected in anomalies in the immune system parameters. Increasing evidence suggests the involvement of immune dysregulation and neuroinflammation in the pathogenesis of schizophrenia. In this systematic review, we summarized the available evidence of abnormalities in the immune system in schizophrenia. We analyzed impairments in all immune system components and assessed the level of bias in the available evidence. It has been shown that schizophrenia is associated with abnormalities in all immune system components: from innate to adaptive immunity and from humoral to cellular immunity. Abnormalities in the immune organs have also been observed in schizophrenia. Evidence of increased C-reactive protein, dysregulation of cytokines and chemokines, elevated levels of neutrophils and autoantibodies, and microbiota dysregulation in schizophrenia have the lowest risk of bias. Peripheral immune abnormalities contribute to neuroinflammation, which is associated with cognitive and neuroanatomical alterations and contributes to the pathogenesis of schizophrenia. However, signs of severe inflammation are observed in only about 1/3 of patients with schizophrenia. Immunological parameters may help identify subgroups of individuals with signs of inflammation who well respond to anti-inflammatory therapy. Our integrative approach also identified gaps in knowledge about immune abnormalities in schizophrenia, and new horizons for the research are proposed.

Identifying novel proteins underlying schizophrenia via integrating pQTLs of the plasma, CSF, and brain with GWAS summary data

“…In the PPI network analysis, we found interactions between proteins from different tissues, and the proteins identified by MR were enriched in the biological process of “immune response” and “inflammatory response.” Therefore, our results further supported that immunity of both the peripheral and central nervous system (CNS) could work together to contribute to neuroinflammation, which is important in the pathogenesis of schizophrenia [ 34 , 35 ].…”

Circulating Cell-Free DNA Levels in Psychiatric Diseases: A Systematic Review and Meta-Analysis

“…The recognition of cfDNA through PRRs is known to trigger an inflammatory response [ 16 , 63 , 64 ]. The chronic proinflammatory state is well documented in schizophrenia [ 17 ], BD [ 18 ], and MDD [ 19 ]. Therefore, based on the data from this meta-analysis, it can be assumed that one of the triggers of chronic low-grade inflammation in schizophrenia is an increased level of cfDNA.…”

“…CfDNA can be recognized by pattern recognition receptors (PRRs) promoting sterile inflammation [ 16 ]. Inflammation is known to be associated with the pathogenesis of severe mental illnesses such as schizophrenia [ 17 ], bipolar disorder (BD) [ 18 ], and depressive disorders (DDs) [ 19 ]. However, the inflammation triggers in psychiatric disorders are still poorly understood, and cfDNA may be one of them.…”

The emerging role of long non-coding RNAs in schizophrenia

“…Immune dysregulation plays an important role in the pathogenesis of SZ ( 23 ). A meta-analysis identified dysregulated cytokine expression in peripheral blood in SZ, which includes interferon-gamma (IFNG) ( 24 ).…”