Peripheral complement is increased in schizophrenia and inversely related to cortical thickness.

Cerebral Cortex / diagnostic imaging Complement System Proteins Cytokines / metabolism Humans Inflammation Magnetic Resonance Imaging / methods RNA, Messenger Schizophrenia
Complement Cortical thickness Cytokines Inflammation Schizophrenia

Journal

Brain, behavior, and immunity
ISSN: 1090-2139
Titre abrégé: Brain Behav Immun
Pays: Netherlands
ID NLM: 8800478

Informations de publication

Date de publication:
03 2022
Historique:
received: 30 07 2021
revised: 23 10 2021
accepted: 15 11 2021
pubmed: 23 11 2021
medline: 26 4 2022
entrez: 22 11 2021
Statut: ppublish

Résumé

There is growing evidence for complement system involvement in the pathophysiology of schizophrenia, although the extent and magnitude of complement factor disturbances has not been fully reported. It also remains unclear whether complement abnormalities are characteristic of all patients with schizophrenia or whether they are representative of a subgroup of patients who show signs of heightened inflammation. The aim of the present study was to quantify and compare the levels of a range of complement factors, receptors and regulators in healthy controls and people with schizophrenia and to determine the extent to which the levels of these peripheral molecules relate to measures of brain structure, particularly cortical thickness. Seventy-five healthy controls and 90 patients with schizophrenia or schizoaffective disorder were included in the study. Peripheral blood samples were collected from all participants and mRNA expression was quantified in 20 complement related genes, four complement proteins, as well as for four cytokines. T1-weighted structural MRI scans were acquired and analysed to determine cortical thickness measures. There were significant increases in peripheral mRNA encoding receptors (C5ar1, CR1, CR3a), regulators (CD55, C59) and protein concentrations (C3, C3b, C4) in people with schizophrenia relative to healthy controls. C4a expression was significantly increased in a subgroup of patients displaying elevated peripheral cytokine levels. A higher inflammation index score derived from mRNA expression patterns predicted reductions in cortical thickness in the temporal lobe (superior temporal gyrus, transverse temporal gyrus, fusiform gyrus, insula) in patients with schizophrenia and healthy controls. Analysis of all three major complement pathways supports increased complement activity in schizophrenia and also shows that peripheral C4a up-regulation is related to increased peripheral pro-inflammatory cytokines in healthy controls. Our region-specific, neuroimaging findings linked to an increased peripheral complement mRNA expression pattern suggests a role for complement in cortical thinning. Further studies are required to further clarify clinical and neurobiological consequences of aberrant complement levels in schizophrenia and related psychoses.

Sections du résumé

BACKGROUND
There is growing evidence for complement system involvement in the pathophysiology of schizophrenia, although the extent and magnitude of complement factor disturbances has not been fully reported. It also remains unclear whether complement abnormalities are characteristic of all patients with schizophrenia or whether they are representative of a subgroup of patients who show signs of heightened inflammation. The aim of the present study was to quantify and compare the levels of a range of complement factors, receptors and regulators in healthy controls and people with schizophrenia and to determine the extent to which the levels of these peripheral molecules relate to measures of brain structure, particularly cortical thickness.
METHOD
Seventy-five healthy controls and 90 patients with schizophrenia or schizoaffective disorder were included in the study. Peripheral blood samples were collected from all participants and mRNA expression was quantified in 20 complement related genes, four complement proteins, as well as for four cytokines. T1-weighted structural MRI scans were acquired and analysed to determine cortical thickness measures.
RESULTS
There were significant increases in peripheral mRNA encoding receptors (C5ar1, CR1, CR3a), regulators (CD55, C59) and protein concentrations (C3, C3b, C4) in people with schizophrenia relative to healthy controls. C4a expression was significantly increased in a subgroup of patients displaying elevated peripheral cytokine levels. A higher inflammation index score derived from mRNA expression patterns predicted reductions in cortical thickness in the temporal lobe (superior temporal gyrus, transverse temporal gyrus, fusiform gyrus, insula) in patients with schizophrenia and healthy controls.
CONCLUSIONS
Analysis of all three major complement pathways supports increased complement activity in schizophrenia and also shows that peripheral C4a up-regulation is related to increased peripheral pro-inflammatory cytokines in healthy controls. Our region-specific, neuroimaging findings linked to an increased peripheral complement mRNA expression pattern suggests a role for complement in cortical thinning. Further studies are required to further clarify clinical and neurobiological consequences of aberrant complement levels in schizophrenia and related psychoses.

Identifiants

DOI: 10.1016/j.bbi.2021.11.014 PMID: 34808287
pubmed: 34808287
pii: S0889-1591(21)00610-3
doi: 10.1016/j.bbi.2021.11.014
pii:
doi:

Substances chimiques

Cytokines 0
RNA, Messenger 0
Complement System Proteins 9007-36-7

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

423-434

Informations de copyright

Copyright © 2021 Elsevier Inc. All rights reserved.

Auteurs

Ellen Ji (E)

Psychiatric University Hospital Zurich, Zurich, Switzerland; Neuroscience Research Australia, Sydney, NSW, Australia.

Danny Boerrigter (D)

Neuroscience Research Australia, Sydney, NSW, Australia.

Helen Q Cai (HQ)

Neuroscience Research Australia, Sydney, NSW, Australia; School of Psychiatry, Faculty of Medicine, University of New South Wales, Sydney, NSW, Australia.

David Lloyd (D)

Neuroscience Research Australia, Sydney, NSW, Australia; School of Psychiatry, Faculty of Medicine, University of New South Wales, Sydney, NSW, Australia.

Jason Bruggemann (J)

Neuroscience Research Australia, Sydney, NSW, Australia; School of Psychiatry, Faculty of Medicine, University of New South Wales, Sydney, NSW, Australia; Edith Collins Centre (Translational Research in Alcohol Drugs & Toxicology), Sydney Local Health District, Australia; Speciality of Addiction Medicine, Central Clinical School, Faculty of Medicine and Health, University of Sydney, Australia.

Maryanne O'Donnell (M)

School of Psychiatry, Faculty of Medicine, University of New South Wales, Sydney, NSW, Australia.

Cherrie Galletly (C)

Discipline of Psychiatry, School of Medicine, University of Adelaide, Adelaide, South Australia, Australia; Northern Adelaide Local Health Network, Adelaide, South Australia, Australia; Ramsay Health Care (SA) Mental Health Services, Adelaide, South Australia, Australia.

Andrew Lloyd (A)

Inflammation and Infection Research Centre, University of New South Wales, Sydney, Australia.

Dennis Liu (D)

Discipline of Psychiatry, School of Medicine, University of Adelaide, Adelaide, South Australia, Australia; Northern Adelaide Local Health Network, Adelaide, South Australia, Australia.

Rhoshel Lenroot (R)

Neuroscience Research Australia, Sydney, NSW, Australia; School of Psychiatry, Faculty of Medicine, University of New South Wales, Sydney, NSW, Australia.

Thomas W Weickert (TW)

Neuroscience Research Australia, Sydney, NSW, Australia; School of Psychiatry, Faculty of Medicine, University of New South Wales, Sydney, NSW, Australia; Department of Neuroscience and Physiology, Upstate Medical University, Syracuse, NY, USA.

Cynthia Shannon Weickert (C)

Neuroscience Research Australia, Sydney, NSW, Australia; School of Psychiatry, Faculty of Medicine, University of New South Wales, Sydney, NSW, Australia; Department of Neuroscience and Physiology, Upstate Medical University, Syracuse, NY, USA. Electronic address: c.weickert@neura.edu.au.

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Classifications MeSH

questionsmedicales.fr › Système nerveux › Système nerveux central › Encéphale › Prosencéphale › Télencéphale › Cerveau › Cortex cérébral › Peripheral complement is increased in...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines du sang › Immunoprotéines › Protéines du système du complément › Peripheral complement is increased in...
questionsmedicales.fr › Facteurs biologiques › Protéines et peptides de signalisation intercellulaire › Cytokines › Peripheral complement is increased in...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Peripheral complement is increased in...
questionsmedicales.fr › États, signes et symptômes pathologiques › Processus pathologiques › Inflammation › Peripheral complement is increased in...
questionsmedicales.fr › Diagnostic › Techniques et procédures diagnostiques › Imagerie diagnostique › Tomographie › Imagerie par résonance magnétique › Peripheral complement is increased in...
questionsmedicales.fr › Acides nucléiques, nucléotides et nucléosides › Acides nucléiques › ARN › ARN messager › Peripheral complement is increased in...
questionsmedicales.fr › Troubles mentaux › Schizophrénie et troubles avec traits psychotiques › Schizophrénie › Peripheral complement is increased in...