TY - JOUR

T1 - Immune System Abnormalities in Schizophrenia: An Integrative View and Translational Perspectives

AU - Ermakov, Evgeny A.

AU - Melamud, Mark M.

AU - Buneva, Valentina N.

AU - Ivanova, Svetlana A.

N1 - Funding Information: This work was supported by the Russian Science Foundation under grant 21-75-00102 to EE (Sections “Molecular Components of the Innate Immune System,” “Changes in the Immune System Organs Associated With Schizophrenia,” “Immune-Associated Alterations in the Brain,” and “Overview of the Immune System Abnormalities in Schizophrenia”) and 20-15-00162 to VB (Sections “Cellular Components of the Innate Immune System,” “Changes in the Cellular Components of Adaptive Immunity,” and “Changes in the Molecular Components of Adaptive Immunity: Antibodies and Autoimmunity in Schizophrenia”). Publisher Copyright: Copyright © 2022 Ermakov, Melamud, Buneva and Ivanova.

PY - 2022/4/25

Y1 - 2022/4/25

N2 - 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.

AB - 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.

KW - antibodies

KW - B cell

KW - cytokines

KW - immune system

KW - inflammation

KW - schizophrenia

KW - T cell

UR - http://www.scopus.com/inward/record.url?scp=85129942313&partnerID=8YFLogxK

UR - https://www.mendeley.com/catalogue/37d25cbf-201f-33c2-8286-d9bb77a2e33c/

U2 - 10.3389/fpsyt.2022.880568

DO - 10.3389/fpsyt.2022.880568

M3 - Review article

C2 - 35546942

AN - SCOPUS:85129942313

VL - 13

JO - Frontiers in Psychiatry

JF - Frontiers in Psychiatry

SN - 1664-0640

M1 - 880568

ER -