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Altered Complement System Activity in Schizophrenia: Overexpression of C4 and/or Abnormal Expression of Complement Control Proteins in the DLPFC, Parietal Cortex, Temporal Cortex, Associative Striatum, Hippocampus, Cerebellum and Whole Blood

Published online by Cambridge University Press:  01 September 2022

R. Rey  and
M. Leboyer
R. Rey*
Affiliation:
INSERM, U1028; CNRS, UMR5292; Lyon Neuroscience Research Center, Psychiatric Disorders: from Resistance to Response Team, Lyon, F-69000, France, Schizophrenia Expert Center Of Lyon, Bron, France
M. Leboyer
Affiliation:
APHP CHU Mondor, Psychiatrie, Créteil, France
*
*Corresponding author.

Abstract

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Introduction

In schizophrenia, abnormal synaptic pruning during adolescence may be due to an altered Complement system activity. While this hypothesis is supported by C4 overexpression in various brain regions of individuals with schizophrenia, such alterations should be replicated and extended to other brain regions relevant to schizophrenia. Moreover, transcriptional studies of genes coding for proteins regulating the Complement system activity are lacking. Furthermore, it remains unknown whether cerebral and peripheral expression of C4 and Complement control proteins (CCP) are related.

Objectives

To identify altered expression of C4 and CCP (CSMD1, CSMD2, CD46) coding genes at the cerebral and peripheral levels in schizophrenic individuals.

Methods

We explored C4 and CCP coding genes expression at the cerebral and peripheral levels. Using shinyGEO application we analyzed gene expression from eight Gene Expression Omnibus datasets obtained from 196 schizophrenic individuals and 182 control subjects. First, we compared gene expression between schizophrenic patients and controls in postmortem cerebral samples from 7 different brain regions. Then, we compared gene expression between schizophrenic patients and controls in 4 peripheral tissues.

Results

We observed C4 overexpression in the DLPFC, parietal, temporal cortex and associative striatum of schizophrenic individuals. We report altered transcriptional patterns of CCP genes in the DLPFC, hippocampus and cerebellum of schizophrenic individuals. CD46 expression was altered in opposite directions between brain and blood of schizophrenic individuals. No significant alteration of C4 expression was observed in peripheral tissues.

Conclusions

Our results support the hypothesis of an altered Complement system activity in various brain regions of schizophrenic individuals which may disrupt the synaptic pruning process during adolescence.

Disclosure

No significant relationships.

Keywords

Complement systemschizophréniaBrainGene expression
Type
Abstract
Information
European Psychiatry , Volume 65 , Special Issue S1: Abstracts of the 30th European Congress of Psychiatry , June 2022 , pp. S366
Creative Commons
Creative Common License - CCCreative Common License - BY
This is an Open Access article, distributed under the terms of the Creative Commons Attribution licence (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted re-use, distribution, and reproduction in any medium, provided the original work is properly cited.
Copyright
© The Author(s), 2022. Published by Cambridge University Press on behalf of the European Psychiatric Association
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