CX3CR1 is dysregulated in blood and brain from schizophrenia patients.
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.
INSERM, TAGC UMR_S 1090, 13288 Marseille Cedex 09, France; Aix Marseille Université, TAGC UMR_S 1090, 13288 Marseille Cedex 09, France.
Aurélie
A
Bergon
Aix Marseille Université, CNRS, CRN2M UMR 7286, 13344 Marseille Cedex 15, France; FondaMental, Fondation de Recherche et de Soins en Santé Mentale, 94000 Créteil, France; AP-HM, Hôpital Sainte Marguerite, Pôle de Psychiatrie Universitaire Solaris, 13009 Marseille, France.
Raoul
R
Belzeaux
Aix-Marseille Université, CNRS, Institut de Neurosciences de la Timone UMR 7289, 13005 Marseille, France.
Magali
M
Comte
Aix Marseille Université, CNRS, CRN2M UMR 7286, 13344 Marseille Cedex 15, France; FondaMental, Fondation de Recherche et de Soins en Santé Mentale, 94000 Créteil, France.
Florence
F
Pelletier
Aix Marseille Université, CNRS, CRN2M UMR 7286, 13344 Marseille Cedex 15, France; FondaMental, Fondation de Recherche et de Soins en Santé Mentale, 94000 Créteil, France.
Mylène
M
Hervé
School of Biomedical Sciences and Pharmacy and School of Medicine and Public Health, Faculty of Health, The University of Newcastle, University Drive, Callaghan, NSW 2308 Australia; Centre for Translational Neuroscience and Mental Health, The University of Newcastle, Callaghan, NSW 2308 Australia; Hunter Medical Research Institute, New Lambton Heights, NSW 2305, Australia; Schizophrenia Research Institute, Darlinghurst, NSW 2010 Australia.
Erin J
EJ
Gardiner
School of Biomedical Sciences and Pharmacy and School of Medicine and Public Health, Faculty of Health, The University of Newcastle, University Drive, Callaghan, NSW 2308 Australia; Centre for Translational Neuroscience and Mental Health, The University of Newcastle, Callaghan, NSW 2308 Australia; Hunter Medical Research Institute, New Lambton Heights, NSW 2305, Australia; Schizophrenia Research Institute, Darlinghurst, NSW 2010 Australia.
Natalie J
NJ
Beveridge
School of Biomedical Sciences and Pharmacy and School of Medicine and Public Health, Faculty of Health, The University of Newcastle, University Drive, Callaghan, NSW 2308 Australia; Centre for Translational Neuroscience and Mental Health, The University of Newcastle, Callaghan, NSW 2308 Australia; Kids Cancer Alliance, Cancer Institute NSW, Sydney, Australia.
Bing
B
Liu
Schizophrenia Research Institute, Darlinghurst, NSW 2010 Australia; School of Psychiatry, University of New South Wales, Randwick, NSW 2301, Australia; Department of Psychiatry, Monash University, Clayton, VIC 3168, Australia.
Vaughan
V
Carr
School of Biomedical Sciences and Pharmacy and School of Medicine and Public Health, Faculty of Health, The University of Newcastle, University Drive, Callaghan, NSW 2308 Australia; Centre for Translational Neuroscience and Mental Health, The University of Newcastle, Callaghan, NSW 2308 Australia; Hunter Medical Research Institute, New Lambton Heights, NSW 2305, Australia; Schizophrenia Research Institute, Darlinghurst, NSW 2010 Australia.
Rodney J
RJ
Scott
School of Biomedical Sciences and Pharmacy and School of Medicine and Public Health, Faculty of Health, The University of Newcastle, University Drive, Callaghan, NSW 2308 Australia; Centre for Translational Neuroscience and Mental Health, The University of Newcastle, Callaghan, NSW 2308 Australia; Hunter Medical Research Institute, New Lambton Heights, NSW 2305, Australia.
Brian
B
Kelly
School of Biomedical Sciences and Pharmacy and School of Medicine and Public Health, Faculty of Health, The University of Newcastle, University Drive, Callaghan, NSW 2308 Australia; Centre for Translational Neuroscience and Mental Health, The University of Newcastle, Callaghan, NSW 2308 Australia; Hunter Medical Research Institute, New Lambton Heights, NSW 2305, Australia; Schizophrenia Research Institute, Darlinghurst, NSW 2010 Australia.
Murray J
MJ
Cairns
School of Biomedical Sciences and Pharmacy and School of Medicine and Public Health, Faculty of Health, The University of Newcastle, University Drive, Callaghan, NSW 2308 Australia; Centre for Translational Neuroscience and Mental Health, The University of Newcastle, Callaghan, NSW 2308 Australia; Hunter Medical Research Institute, New Lambton Heights, NSW 2305, Australia; Schizophrenia Research Institute, Darlinghurst, NSW 2010 Australia; University of Sri Jayewardenepura, Nugegoda, Sri Lanka; National Institute of Mental Health, Angoda, Sri Lanka.
Nishantha
N
Kumarasinghe
School of Biomedical Sciences and Pharmacy and School of Medicine and Public Health, Faculty of Health, The University of Newcastle, University Drive, Callaghan, NSW 2308 Australia; Centre for Translational Neuroscience and Mental Health, The University of Newcastle, Callaghan, NSW 2308 Australia; Hunter Medical Research Institute, New Lambton Heights, NSW 2305, Australia; Schizophrenia Research Institute, Darlinghurst, NSW 2010 Australia.
Ulrich
U
Schall
CIC-UPCET et Pharmacologie Clinique, Hôpital de la Timone, 13005 Marseille, France.
Olivier
O
Blin
Aix Marseille Université, CNRS, CRN2M UMR 7286, 13344 Marseille Cedex 15, France; FondaMental, Fondation de Recherche et de Soins en Santé Mentale, 94000 Créteil, France.
José
J
Boucraut
School of Biomedical Sciences and Pharmacy and School of Medicine and Public Health, Faculty of Health, The University of Newcastle, University Drive, Callaghan, NSW 2308 Australia; Centre for Translational Neuroscience and Mental Health, The University of Newcastle, Callaghan, NSW 2308 Australia; Hunter Medical Research Institute, New Lambton Heights, NSW 2305, Australia; Schizophrenia Research Institute, Darlinghurst, NSW 2010 Australia.
Paul A
PA
Tooney
Aix-Marseille Université, CNRS, Institut de Neurosciences de la Timone UMR 7289, 13005 Marseille, France; CHU de Saint-Etienne, Pôle de Psychiatrie, 42100 Saint-Etienne, France.
Eric
E
Fakra
Aix Marseille Université, CNRS, CRN2M UMR 7286, 13344 Marseille Cedex 15, France; FondaMental, Fondation de Recherche et de Soins en Santé Mentale, 94000 Créteil, France. Electronic address: el-cherif.ibrahim@univ-amu.fr.
El Chérif
EC
Ibrahim
D000328:Adult; D014150:Antipsychotic Agents / Q000627:therapeutic use; D015415:Biomarkers / Q000378:metabolism; D001921:Brain / Q000378:metabolism*; D000073883:CX3C Chemokine Receptor 1; D015331:Cohort Studies; D015536:Down-Regulation; D005260:Female; D006801:Humans; D008297:Male; D046228:Microarray Analysis; D008875:Middle Aged; D060888:Real-Time Polymerase Chain Reaction; D019707:Receptors, Chemokine / Q000378:metabolism*; D012559:Schizophrenia / Q000188:drug therapy / Q000378:metabolism*
D014150:Antipsychotic Agents; D015415:Biomarkers; D000073883:CX3C Chemokine Receptor 1; C095235:CX3CR1 protein, human; D019707:Receptors, Chemokine
CX3CR1; Inflammation; Meta-analysis; Schizophrenia; Transcriptomics; mRNA