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Meta-Analysis
. 2015 Oct;168(1-2):434-43.
doi: 10.1016/j.schres.2015.08.010. Epub 2015 Aug 15.

CX3CR1 is dysregulated in blood and brain from schizophrenia patients

Aurélie Bergon  1 , Raoul Belzeaux  2 , Magali Comte  3 , Florence Pelletier  4 , Mylène Hervé  4 , Erin J Gardiner  5 , Natalie J Beveridge  5 , Bing Liu  6 , Vaughan Carr  7 , Rodney J Scott  5 , Brian Kelly  8 , Murray J Cairns  5 , Nishantha Kumarasinghe  9 , Ulrich Schall  5 , Olivier Blin  10 , José Boucraut  4 , Paul A Tooney  5 , Eric Fakra  11 , El Chérif Ibrahim  12
Affiliations
Meta-Analysis

CX3CR1 is dysregulated in blood and brain from schizophrenia patients

Aurélie Bergon et al. Schizophr Res. 2015 Oct.

Abstract

The molecular mechanisms underlying schizophrenia remain largely unknown. Although schizophrenia is a mental disorder, there is increasing evidence to indicate that inflammatory processes driven by diverse environmental factors play a significant role in its development. With gene expression studies having been conducted across a variety of sample types, e.g., blood and postmortem brain, it is possible to investigate convergent signatures that may reveal interactions between the immune and nervous systems in schizophrenia pathophysiology. We conducted two meta-analyses of schizophrenia microarray gene expression data (N=474) and non-psychiatric control (N=485) data from postmortem brain and blood. Then, we assessed whether significantly dysregulated genes in schizophrenia could be shared between blood and brain. To validate our findings, we selected a top gene candidate and analyzed its expression by RT-qPCR in a cohort of schizophrenia subjects stabilized by atypical antipsychotic monotherapy (N=29) and matched controls (N=31). Meta-analyses highlighted inflammation as the major biological process associated with schizophrenia and that the chemokine receptor CX3CR1 was significantly down-regulated in schizophrenia. This differential expression was also confirmed in our validation cohort. Given both the recent data demonstrating selective CX3CR1 expression in subsets of neuroimmune cells, as well as behavioral and neuropathological observations of CX3CR1 deficiency in mouse models, our results of reduced CX3CR1 expression adds further support for a role played by monocyte/microglia in the neurodevelopment of schizophrenia.

Keywords: CX3CR1; Inflammation; Meta-analysis; Schizophrenia; Transcriptomics; mRNA.

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