Toll-Like Receptor mRNA Levels in Schizophrenia: Association With Complement Factors and Cingulate Gyrus Cortical Thinning.

complement factors cortical thickness innate immunity magnetic resonance imaging schizophrenia toll like receptors

Journal

Schizophrenia bulletin
ISSN: 1745-1701
Titre abrégé: Schizophr Bull
Pays: United States
ID NLM: 0236760

Informations de publication

Date de publication:
15 Dec 2023
Historique:
medline: 16 12 2023
pubmed: 16 12 2023
entrez: 16 12 2023
Statut: aheadofprint

Résumé

Previous studies revealed innate immune system activation in people with schizophrenia (SZ), potentially mediated by endogenous pathogen recognition receptors, notably Toll-like receptors (TLR). TLRs are activated by pathogenic molecules like bacterial lipopolysaccharides (TLR1 and TLR4), viral RNA (TLR3), or both (TLR8). Furthermore, the complement system, another key component of innate immunity, has previously been linked to SZ. Peripheral mRNA levels of TLR1, TLR3, TLR4, and TLR8 were compared between SZ and healthy controls (HC). We investigated their relationship with immune activation through complement expression and cortical thickness of the cingulate gyrus, a region susceptible to immunological hits. TLR mRNA levels and peripheral complement receptor mRNA were extracted from 86 SZ and 77 HC white blood cells; structural MRI scans were conducted on a subset. We found significantly higher TLR4 and TLR8 mRNA levels and lower TLR3 mRNA levels in SZ compared to HC. TLRs and complemental factors were significantly associated in SZ and HC, with the strongest deviations of TLR mRNA levels in the SZ subgroup having elevated complement expression. Cortical thickness of the cingulate gyrus was inversely associated with TLR8 mRNA levels in SZ, and with TLR4 and TLR8 levels in HC. The study underscores the role of innate immune activation in schizophrenia, indicating a coordinated immune response of TLRs and the complement system. Our results suggest there could be more bacterial influence (based on TLR 4 levels) as opposed to viral influence (based on TLR3 levels) in schizophrenia. Specific TLRs were associated with brain cortical thickness reductions of limbic brain structures.

Sections du résumé

BACKGROUND AND HYPOTHESES UNASSIGNED
Previous studies revealed innate immune system activation in people with schizophrenia (SZ), potentially mediated by endogenous pathogen recognition receptors, notably Toll-like receptors (TLR). TLRs are activated by pathogenic molecules like bacterial lipopolysaccharides (TLR1 and TLR4), viral RNA (TLR3), or both (TLR8). Furthermore, the complement system, another key component of innate immunity, has previously been linked to SZ.
STUDY DESIGN METHODS
Peripheral mRNA levels of TLR1, TLR3, TLR4, and TLR8 were compared between SZ and healthy controls (HC). We investigated their relationship with immune activation through complement expression and cortical thickness of the cingulate gyrus, a region susceptible to immunological hits. TLR mRNA levels and peripheral complement receptor mRNA were extracted from 86 SZ and 77 HC white blood cells; structural MRI scans were conducted on a subset.
STUDY RESULTS RESULTS
We found significantly higher TLR4 and TLR8 mRNA levels and lower TLR3 mRNA levels in SZ compared to HC. TLRs and complemental factors were significantly associated in SZ and HC, with the strongest deviations of TLR mRNA levels in the SZ subgroup having elevated complement expression. Cortical thickness of the cingulate gyrus was inversely associated with TLR8 mRNA levels in SZ, and with TLR4 and TLR8 levels in HC.
CONCLUSIONS CONCLUSIONS
The study underscores the role of innate immune activation in schizophrenia, indicating a coordinated immune response of TLRs and the complement system. Our results suggest there could be more bacterial influence (based on TLR 4 levels) as opposed to viral influence (based on TLR3 levels) in schizophrenia. Specific TLRs were associated with brain cortical thickness reductions of limbic brain structures.

Identifiants

DOI: 10.1093/schbul/sbad171 PMID: 38102721
pubmed: 38102721
pii: 7475810
doi: 10.1093/schbul/sbad171
pii:
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Subventions

Organisme : University of New South Wales School of Psychiatry; National Health and Medical Research Council
ID : 568807
Organisme : National Health and Medical Research Council
ID : 1021970
Organisme : Swiss National fund
ID : P3SMP3 148381

Informations de copyright

© The Author(s) 2023. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Auteurs

Thomas W Weickert (TW)

Neuroscience Research Australia, Schizophrenia Research Institute, Randwick, NSW 2031, Australia.
School of Psychiatry, University of New South Wales, Randwick, NSW 2031 Australia.
Department of Neuroscience and Physiology, Upstate Medical University, Syracuse, NY 13210, USA.

Ellen Ji (E)

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

Cherrie Galletly (C)

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

Danny Boerrigter (D)

Neuroscience Research Australia, Schizophrenia Research Institute, Randwick, NSW 2031, Australia.

Yosuke Morishima (Y)

Translational Research Center, University Hospital of Psychiatry, University of Bern, Bern, Switzerland.

Jason Bruggemann (J)

Neuroscience Research Australia, Schizophrenia Research Institute, Randwick, NSW 2031, Australia.
School of Psychiatry, University of New South Wales, Randwick, NSW 2031 Australia.
Edith Collins Centre (Translational Research in Alcohol Drugs and Toxicology), Sydney Local Health District, Sydney, Australia.
Speciality of Addiction Medicine, Central Clinical School, Faculty of Medicine and Health, University of Sydney, Sydney, Australia.

Ryan Balzan (R)

School of Psychology, Flinders University, Adelaide, SA, Australia.

Maryanne O'Donnell (M)

Neuroscience Research Australia, Schizophrenia Research Institute, Randwick, NSW 2031, Australia.
Kiloh Centre, Prince of Wales Hospital, Randwick, New South Wales, Australia.

Dennis Liu (D)

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

Rhoshel Lenroot (R)

Neuroscience Research Australia, Schizophrenia Research Institute, Randwick, NSW 2031, Australia.
School of Psychiatry, University of New South Wales, Randwick, NSW 2031 Australia.
Department of Psychiatry, University of New Mexico, Albuquerque, NM 87131-0001, USA.

Cynthia Shannon Weickert (CS)

Neuroscience Research Australia, Schizophrenia Research Institute, Randwick, NSW 2031, Australia.
School of Psychiatry, University of New South Wales, Randwick, NSW 2031 Australia.
Department of Neuroscience and Physiology, Upstate Medical University, Syracuse, NY 13210, USA.

Jochen Kindler (J)

Neuroscience Research Australia, Schizophrenia Research Institute, Randwick, NSW 2031, Australia.
University Hospital of Child and Adolescent Psychiatry and Psychotherapy, University of Bern, 3000 Bern, Switzerland.

Classifications MeSH