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Type: Journal article
Title: Increased macrophages and changed brain endothelial cell gene expression in the frontal cortex of people with schizophrenia displaying inflammation
Author: Cai, H.Q.
Catts, V.S.
Webster, M.J.
Galletly, C.
Liu, D.
O Donnell, M.
Weickert, T.W.
Weickert, C.S.
Citation: Molecular Psychiatry, 2020; 25(4):761-775
Publisher: Springer Nature
Issue Date: 2020
ISSN: 1359-4184
Statement of
Helen Q. Cai, Vibeke S. Catts, Maree J. Webster, Cherrie Galletly, Dennis Liu, Maryanne O, Donnell, Thomas W Weickert, Cynthia Shannon Weickert
Abstract: Elevated pro-inflammatory cytokines exist in both blood and brain of people with schizophrenia but how this affects molecular indices of the blood-brain barrier (BBB) is unclear. Eight mRNAs relating to BBB function, a microglia and three immune cell markers were measured by qPCR in the prefrontal cortex from 37 people with schizophrenia/schizoaffective disorder and 37 matched controls. This cohort was previously grouped into "high inflammation" and "low inflammation" subgroups based on cortical inflammatory-related transcripts. Soluble intercellular adhesion molecule-1 (sICAM1) was measured in the plasma of 78 patients with schizophrenia/schizoaffective disorder and 73 healthy controls. We found that sICAM1 was significantly elevated in schizophrenia. An efflux transporter, ABCG2, was lower, while mRNAs encoding VE-cadherin and ICAM1 were higher in schizophrenia brain. The "high inflammation" schizophrenia subgroup had lower ABCG2 and higher ICAM1, VE-cadherin, occludin and interferon-induced transmembrane protein mRNAs compared to both "low inflammation" schizophrenia and "low inflammation" control subgroups. ICAM1 immunohistochemistry showed enrichment in brain endothelium regardless of diagnosis and was localised to astrocytes in some brains. Microglia mRNA was not altered in schizophrenia nor did it correlate with ICAM1 expression. Immune cell mRNAs were elevated in "high inflammation" schizophrenia compared to both "low inflammation" schizophrenia and controls. CD163+ perivascular macrophages were identified by immunohistochemistry in brain parenchyma in over 40% of "high inflammation" schizophrenia brains. People with high levels of cytokine expression and schizophrenia display changes consistent with greater immune cell transmigration into brain via increased ICAM1, which could contribute to other neuropathological changes found in this subgroup of people.
Keywords: Blood-Brain Barrier; Brain; Frontal Lobe; Prefrontal Cortex; Astrocytes; Microglia; Endothelium; Macrophages; Endothelial Cells; Humans; Encephalitis; Inflammation; Intercellular Adhesion Molecule-1; Psychotic Disorders; Schizophrenia; Gene Expression; Adult; Middle Aged; Female; Male; Biomarkers
Rights: © The Author(s) 2018. This article is published with open access. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit
RMID: 0030102966
DOI: 10.1038/s41380-018-0235-x
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