Journal
MOLECULAR PSYCHIATRY
Volume 25, Issue 4, Pages 761-775Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/s41380-018-0235-x
Keywords
-
Funding
- NSW Ministry of Health, Office of Health and Medical Research
- National Health and Medical Research Council (Australia) Principal Research Fellowship (PRF) [1117079]
- Australian Government Research Training Program Scholarship from the University of New South Wales
- Neuroscience Research Australia
- University of Sydney
- Schizophrenia Research Institute
- National Institute of Alcohol Abuse and Alcoholism of the National Institutes of Health [R28AA012725]
- National Health and Medical Research Council (NHMRC) of Australia [568807]
Ask authors/readers for more resources
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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available