Evidence map›Paper›PMID 30940904›Full record

ArticleMolecular psychiatry2020

Dysregulation of kynurenine metabolism is related to proinflammatory cytokines, attention, and prefrontal cortex volume in schizophrenia.

Jochen Kindler, Chai K Lim, Cynthia Shannon Weickert, Danny Boerrigter, Cherrie Galletly, Dennis Liu, Kelly R Jacobs, Ryan Balzan, Jason Bruggemann, Maryanne O'Donnell and 3 more

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

Article in Molecular psychiatry, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 147 papers, 13 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
147citing papers in PubMed, 13 pooled it
10.3field-weighted citation impact, top 1% 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

147 citing papers in PubMed, 13 syntheses or guidelines pooled it, 281 citations in OpenAlex.

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  12. BrainFrontiers in immunology · 2021
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87 more citing papers are in PubMed but not listed here.

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

13 authors at 7 institutions in 2 countries.

Jochen Kindler *School of Psychiatry, University of New South Wales, Randwick, NSW, 2031, Australia.
Chai K Lim *Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Macquarie University, Sydney, NSW, 2109, Australia.ORCID http://orcid.org/0000-0003-3526-8405
Cynthia Shannon WeickertSchool of Psychiatry, University of New South Wales, Randwick, NSW, 2031, Australia.
Danny BoerrigterNeuroscience Research Australia, Randwick, NSW, 2031, Australia.
Cherrie GalletlyDiscipline of Psychiatry, School of Medicine, University of Adelaide, Adelaide, SA, Australia.
Dennis LiuDiscipline of Psychiatry, School of Medicine, University of Adelaide, Adelaide, SA, Australia.
Kelly R JacobsDepartment of Biomedical Sciences, Faculty of Medicine and Health Sciences, Macquarie University, Sydney, NSW, 2109, Australia.
Ryan BalzanCollege of Education, Psychology, and Social Work, Flinders University, Adelaide, SA, Australia.
Jason BruggemannSchool of Psychiatry, University of New South Wales, Randwick, NSW, 2031, Australia.
Maryanne O'DonnellSchool of Psychiatry, University of New South Wales, Randwick, NSW, 2031, Australia.
Rhoshel LenrootSchool of Psychiatry, University of New South Wales, Randwick, NSW, 2031, Australia.
Gilles J Guillemin *Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Macquarie University, Sydney, NSW, 2109, Australia.
Thomas W Weickert *School of Psychiatry, University of New South Wales, Randwick, NSW, 2031, Australia. t.weickert@unsw.edu.au.ORCID http://orcid.org/0000-0002-6408-718X
UNSW Sydney · AUMacquarie University · AUFlinders University · AUSA Health · AUSchizophrenia Research Institute · AUThe University of Adelaide · AUUniversity of Bern · CH

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The kynurenine pathway (KP) of tryptophan (TRP) catabolism links immune system activation with neurotransmitter signaling. The KP metabolite kynurenic acid (KYNA) is increased in the brains of people with schizophrenia. We tested the extent to which: (1) brain KP enzyme mRNAs, (2) brain KP metabolites, and (3) plasma KP metabolites differed on the basis of elevated cytokines in schizophrenia vs. control groups and the extent to which plasma KP metabolites were associated with cognition and brain volume in patients displaying elevated peripheral cytokines. KP enzyme mRNAs and metabolites were assayed in two independent postmortem brain samples from a total of 71 patients with schizophrenia and 72 controls. Plasma KP metabolites, cognition, and brain volumes were measured in an independent cohort of 96 patients with schizophrenia and 81 healthy controls. Groups were stratified based on elevated vs. normal proinflammatory cytokine mRNA levels. In the prefrontal cortex (PFC), kynurenine (KYN)/TRP ratio, KYNA levels, and mRNA for enzymes, tryptophan dioxygenase (TDO) and kynurenine aminotransferases (KATI/II), were significantly increased in the high cytokine schizophrenia subgroup. KAT mRNAs significantly correlated with mRNA for glial fibrillary acidic protein in patients. In plasma, the high cytokine schizophrenia subgroup displayed an elevated KYN/TRP ratio, which correlated inversely with attention and dorsolateral prefrontal cortex (DLPFC) volume. This study provides further evidence for the role of inflammation in a subgroup of patients with schizophrenia and suggests a molecular mechanism through which inflammation could lead to schizophrenia. Proinflammatory cytokines may elicit conversion of TRP to KYN in the periphery and increase the N-methyl-D-aspartate receptor antagonist KYNA via increased KAT mRNA and possibly more enzyme synthesis activity in brain astrocytes,  leading to DLPFC volume loss, and attention impairment in schizophrenia.

Indexed as

AttentionAdultCytokinesFemaleHumansInflammation MediatorsKynurenic AcidKynurenineMaleMiddle AgedPrefrontal CortexSchizophreniaYoung AdultCytokinesInflammation MediatorsKynurenic AcidKynurenine

Identifiers

PMID30940904
PMCPMC7577855
OpenAlexW2929017669

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.