Evidence map›Paper›PMID 38102721›Full record

ArticleSchizophrenia bulletin2024

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

Thomas W Weickert, Ellen Ji, Cherrie Galletly, Danny Boerrigter, Yosuke Morishima, Jason Bruggemann, Ryan Balzan, Maryanne O'Donnell, Dennis Liu, Rhoshel Lenroot and 2 more

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Schizophrenia bulletin, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed, 1 pooled it
1.0field-weighted citation impact, top 27% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

6 citing papers in PubMed, 1 synthesis or guideline pooled it, 10 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Article
  4. Review
  5. Review
  6. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors at 6 institutions in 3 countries.

Thomas W WeickertNeuroscience Research Australia, Schizophrenia Research Institute, Randwick, NSW 2031, Australia.
Ellen JiPsychiatric University Hospital Zurich, Zurich, Switzerland.
Cherrie GalletlyDiscipline of Psychiatry, School of Medicine, University of Adelaide, Adelaide, SA, Australia.
Danny BoerrigterNeuroscience Research Australia, Schizophrenia Research Institute, Randwick, NSW 2031, Australia.
Yosuke MorishimaTranslational Research Center, University Hospital of Psychiatry, University of Bern, Bern, Switzerland.
Jason BruggemannNeuroscience Research Australia, Schizophrenia Research Institute, Randwick, NSW 2031, Australia.
Ryan BalzanSchool of Psychology, Flinders University, Adelaide, SA, Australia.
Maryanne O'DonnellNeuroscience Research Australia, Schizophrenia Research Institute, Randwick, NSW 2031, Australia.
Dennis LiuDiscipline of Psychiatry, School of Medicine, University of Adelaide, Adelaide, SA, Australia.
Rhoshel LenrootNeuroscience Research Australia, Schizophrenia Research Institute, Randwick, NSW 2031, Australia.
Cynthia Shannon WeickertNeuroscience Research Australia, Schizophrenia Research Institute, Randwick, NSW 2031, Australia.
Jochen KindlerNeuroscience Research Australia, Schizophrenia Research Institute, Randwick, NSW 2031, Australia.
Neuroscience Research Australia · AUSchizophrenia Research Institute · AUUniversity of Adelaide · AUUNSW Sydney · AUFlinders University · AUUniversity of Bern · CH

Funding

National Health and Medical Research Council 1021970Swiss National fund P3SMP3 148381University of New South Wales School of Psychiatry; National Health and Medical Research Council 568807
6 · The paper itself

Abstract

background and hypothesesPrevious 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

designPeripheral 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

resultsWe 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.

conclusionsThe 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.

Indexed as

SchizophreniaToll-Like Receptor 3Toll-Like Receptor 4Toll-Like Receptor 8Cerebral Cortical ThinningGyrus CinguliHumansRNA, MessengerToll-Like Receptor 1Toll-Like Receptor 7Toll-Like Receptor 9Toll-Like ReceptorsRNA, MessengerToll-Like Receptor 1Toll-Like Receptor 3Toll-Like Receptor 4Toll-Like Receptor 7Toll-Like Receptor 8Toll-Like Receptor 9Toll-Like Receptorscomplement factorscortical thicknessinnate immunitymagnetic resonance imagingschizophreniatoll like receptors

Identifiers

PMID38102721
PMCPMC10919782
OpenAlexW4389834026

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.