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@ARTICLE{North:165283,
author = {North, Hayley F and Weissleder, Christin and Fullerton,
Janice M and Webster, Maree J and Weickert, Cynthia Shannon},
title = {{I}ncreased immune cell and altered microglia and
neurogenesis transcripts in an {A}ustralian schizophrenia
subgroup with elevated inflammation.},
journal = {Schizophrenia research},
volume = {248},
issn = {0920-9964},
address = {Amsterdam [u.a.]},
publisher = {Elsevier Science},
reportid = {DZNE-2022-01576},
pages = {208 - 218},
year = {2022},
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.},
keywords = {Humans / Microglia: metabolism / Schizophrenia: genetics /
Schizophrenia: metabolism / Follow-Up Studies / Australia /
Neurogenesis: physiology / Inflammation: metabolism / RNA,
Messenger: metabolism / RNA / Glia (Other) / Macrophages
(Other) / Post-mortem (Other) / Psychosis (Other) / Subtype
(Other) / Subventricular zone (Other)},
cin = {AG Deleidi},
ddc = {610},
cid = {I:(DE-2719)1210011},
pnm = {352 - Disease Mechanisms (POF4-352)},
pid = {G:(DE-HGF)POF4-352},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:36108465},
doi = {10.1016/j.schres.2022.08.025},
url = {https://pub.dzne.de/record/165283},
}