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Review
. 2023 Aug 19;12(16):2099.
doi: 10.3390/cells12162099.

Microglia and Other Cellular Mediators of Immunological Dysfunction in Schizophrenia: A Narrative Synthesis of Clinical Findings

Khoa D Nguyen  1   2 , Andrea Amerio  3   4 , Andrea Aguglia  3   4 , Luca Magnani  5 , Alberto Parise  6 , Benedetta Conio  3   4 , Gianluca Serafini  3   4 , Mario Amore  3   4 , Alessandra Costanza  7   8   9
Affiliations
Review

Microglia and Other Cellular Mediators of Immunological Dysfunction in Schizophrenia: A Narrative Synthesis of Clinical Findings

Khoa D Nguyen et al. Cells. .

Abstract

Schizophrenia is a complex psychiatric condition that may involve immune system dysregulation. Since most putative disease mechanisms in schizophrenia have been derived from genetic association studies and fluid-based molecular analyses, this review aims to summarize the emerging evidence on clinical correlates to immune system dysfunction in this psychiatric disorder. We conclude this review by attempting to develop a unifying hypothesis regarding the relative contributions of microglia and various immune cell populations to the development of schizophrenia. This may provide important translational insights that can become useful for addressing the multifaceted clinical presentation of schizophrenia.

Keywords: clinical correlates; immunological dysfunction; microglia; neuroinflammation; schizophrenia.

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Conflict of interest statement

KDN is the scientific founder of Tranquis Therapeutics, a biotechnology company that develops novel treatments for neuroinflammatory and neurodegenerative diseases. KDN is also a scientific advisor for Tochikunda, a biotechnology company that develops SARS-CoV-2 diagnostic devices. All other authors declare no conflicts of interest and that they have no commercial associations (e.g., consultancies, stock ownership, equity interest, patent/licensing arrangement, etc.) that might pose a conflict of interest in connection with the submitted article.

Figures

Figure 1
Figure 1
Immunological disturbances in the central nervous system (CNS) of patients with schizophrenia (SCZ). Region-specific immunological changes in CNS tissues of SCZ patients are characterized by (1) elevated expression of various activation markers of microglia (S100/A8, HLA-DR), decreased expression of neuroprotective quinolinic acid (QA), and increased microgliosis (IBA-1 density); (2) increased expression of macrophage markers (CD14 and CD163); (3) dynamic trafficking of various T cell populations (CD3/CD4/CD8); and (4) CD20+ B cell accumulation and altered B cell receptor (BCR) repertoire. Abbreviations: ACC: anterior cingulate cortex; CSF: cerebrospinal fluid; DPFC: dorsal prefrontal cortex; FC: frontal cortex; HP: hippocampus; SEZ: subependymal zone. Red font indicates discrepancies among studies.
Figure 2
Figure 2
Peripheral immune alterations in patients with schizophrenia (SCZ). Major changes in immune cell types in blood samples of SCZ patients included: (1) Alterations in monocytes such as increased monocyte-to-lymphocyte and monocyte to HDL ratios (MLR and MHR), changes in expression of various immunometabolic markers (TREM1/2, HLA-DR, CD36, reactive oxygen species [ROS], GLUT1), and abnormalities in phagocytosis and cytokine production; (2) elevated expression of various neutrophil-associated markers such as neutrophil to lymphocyte ratio (NLR), oxidative stress, and phagocytosis; (3) presence of various autoantibody-producing pathogenic B cell clones, as well as increased numbers of different B cell subsets; and (4) increased activation profile of T cells (CD25), alterations in oxidative stress and T cell receptor [76] repertoire, and accumulation of immunoregulatory T lymphocyte populations, such as regulatory T (Treg), IL17-producing T-helper (Th17), and mucosal-associated invariant T (MAIT) cells. Red font indicates discrepancies among studies.
See this image and copyright information in PMC

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