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

Weickert, Thomas W; Ji, Ellen; Galletly, Cherrie; Boerrigter, Danny; Morishima, Yosuke; Bruggemann, Jason; Balzan, Ryan; O'Donnell, Maryanne; Liu, Dennis; Lenroot, Rhoshel; Weickert, Cynthia Shannon; Kindler, Jochen (2024). Toll-Like Receptor mRNA Levels in Schizophrenia: Association With Complement Factors and Cingulate Gyrus Cortical Thinning. Schizophrenia bulletin, 50(2), pp. 403-417. Oxford University Press 10.1093/schbul/sbad171

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BACKGROUND AND HYPOTHESES

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

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

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

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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > University Psychiatric Services > University Hospital of Child and Adolescent Psychiatry and Psychotherapy
04 Faculty of Medicine > University Psychiatric Services > University Hospital of Psychiatry and Psychotherapy > Translational Research Center

UniBE Contributor:

Morishima, Yosuke, Kindler, Jochen

Subjects:

600 Technology > 610 Medicine & health

ISSN:

0586-7614

Publisher:

Oxford University Press

Language:

English

Submitter:

Pubmed Import

Date Deposited:

18 Dec 2023 13:00

Last Modified:

08 Mar 2024 00:14

Publisher DOI:

10.1093/schbul/sbad171

PubMed ID:

38102721

Uncontrolled Keywords:

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

BORIS DOI:

10.48350/190438

URI:

https://boris.unibe.ch/id/eprint/190438

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