Journal Article

DZNE-2022-01576

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Increased immune cell and altered microglia and neurogenesis transcripts in an Australian schizophrenia subgroup with elevated inflammation.

North, H. F. ; Weissleder, C.DZNE* ; Fullerton, J. M. ; Webster, M. J. ; Weickert, C. S.

2022
Elsevier Science Amsterdam [u.a.]

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Please use a persistent id in citations: doi:10.1016/j.schres.2022.08.025

Abstract: We previously identified a subgroup of schizophrenia cases (~40 %) with heightened inflammation in the neurogenic subependymal zone (SEZ) (North et al., 2021b). This schizophrenia subgroup had changes indicating reduced microglial activity, increased peripheral immune cells, increased stem cell dormancy/quiescence and reduced neuronal precursor cells. The present follow-up study aimed to replicate and extend those novel findings in an independent post-mortem cohort of schizophrenia cases and controls from Australia. RNA was extracted from SEZ tissue from 20 controls and 22 schizophrenia cases from the New South Wales Brain Tissue Resource Centre, and gene expression analysis was performed. Cluster analysis of inflammation markers (IL1B, IL1R1, SERPINA3 and CXCL8) revealed a high-inflammation schizophrenia subgroup comprising 52 % of cases, which was a significantly greater proportion than the 17 % of high-inflammation controls. Consistent with our previous report (North et al., 2021b), those with high-inflammation and schizophrenia had unchanged mRNA expression of markers for steady-state and activated microglia (IBA1, HEXB, CD68), decreased expression of phagocytic microglia markers (P2RY12, P2RY13), but increased expression of markers for macrophages (CD163), monocytes (CD14), natural killer cells (FCGR3A), and the adhesion molecule ICAM1. Similarly, the high-inflammation schizophrenia subgroup emulated increased quiescent stem cell marker (GFAPD) and decreased neuronal progenitor (DLX6-AS1) and immature neuron marker (DCX) mRNA expression; but also revealed a novel increase in a marker of immature astrocytes (VIM). Replicating primary results in an independent cohort demonstrates that inflammatory subgroups in the SEZ in schizophrenia are reliable, robust and enhance understanding of neuropathological heterogeneity when studying schizophrenia.

Keyword(s): Humans (MeSH) ; Microglia: metabolism (MeSH) ; Schizophrenia: genetics (MeSH) ; Schizophrenia: metabolism (MeSH) ; Follow-Up Studies (MeSH) ; Australia (MeSH) ; Neurogenesis: physiology (MeSH) ; Inflammation: metabolism (MeSH) ; RNA, Messenger: metabolism (MeSH) ; RNA (MeSH) ; Glia ; Macrophages ; Post-mortem ; Psychosis ; Subtype ; Subventricular zone

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Contributing Institute(s):

1. Mitochondria and Inflammation in Neurodegenerative Diseases (AG Deleidi)

Research Program(s):

1. 352 - Disease Mechanisms (POF4-352) (POF4-352)

Appears in the scientific report 2022

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Database coverage:
; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; Current Contents - Social and Behavioral Sciences ; Ebsco Academic Search ; Essential Science Indicators ; IF < 5 ; JCR ; Nationallizenz ; SCOPUS ; Science Citation Index Expanded ; Social Sciences Citation Index ; Web of Science Core Collection

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