Evidence map›Paper›PMID 37735504›Full record

ArticleNeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology2024

Sex- and suicide-specific alterations in the kynurenine pathway in the anterior cingulate cortex in major depression.

Samara J Brown, Katerina Christofides, Christin Weissleder, Xu-Feng Huang, Cynthia Shannon Weickert, Chai K Lim, Kelly A Newell

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

Article in Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
26citing papers in PubMed, 2 pooled it
3.1field-weighted citation impact, top 7% 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

26 citing papers in PubMed, 2 syntheses or guidelines pooled it, 32 citations in OpenAlex.

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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

7 authors at 5 institutions in 3 countries.

Samara J BrownSchool of Medical, Indigenous and Health Sciences and Molecular Horizons, University of Wollongong, Wollongong, NSW, Australia. Samara@uow.edu.au.ORCID http://orcid.org/0000-0003-4442-2515
Katerina ChristofidesNICM Health Research Institute, Western Sydney University, Westmead, NSW, Australia.
Christin WeisslederSchizophrenia Research Laboratory, Neuroscience Research Australia, Randwick, NSW, Australia.
Xu-Feng HuangSchool of Medical, Indigenous and Health Sciences and Molecular Horizons, University of Wollongong, Wollongong, NSW, Australia.ORCID http://orcid.org/0000-0002-5895-2253
Cynthia Shannon WeickertSchizophrenia Research Laboratory, Neuroscience Research Australia, Randwick, NSW, Australia.
Chai K LimSchizophrenia Research Laboratory, Neuroscience Research Australia, Randwick, NSW, Australia.ORCID http://orcid.org/0000-0003-3526-8405
Kelly A NewellSchool of Medical, Indigenous and Health Sciences and Molecular Horizons, University of Wollongong, Wollongong, NSW, Australia. knewell@uow.edu.au.
University of Wollongong · AUInstitut des Maladies Génétiques Imagine · FRNeuroscience Research Australia · AUSUNY Upstate Medical University · USWestmead Institute · AU

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Major depressive disorder (MDD) is a serious psychiatric disorder that in extreme cases can lead to suicide. Evidence suggests that alterations in the kynurenine pathway (KP) contribute to the pathology of MDD. Activation of the KP leads to the formation of neuroactive metabolites, including kynurenic acid (KYNA) and quinolinic acid (QUIN). To test for changes in the KP, postmortem anterior cingulate cortex (ACC) was obtained from the National Institute of Health NeuroBioBank. Gene expression of KP enzymes and relevant neuroinflammatory markers were investigated via RT-qPCR (Fluidigm) and KP metabolites were measured using liquid chromatography-mass spectrometry in tissue from individuals with MDD (n = 44) and matched nonpsychiatric controls (n = 36). We report increased IL6 and IL1B mRNA in MDD. Subgroup analysis found that female MDD subjects had significantly decreased KYNA and a trend decrease in the KYNA/QUIN ratio compared to female controls. In addition, MDD subjects that died by suicide had significantly decreased KYNA in comparison to controls and MDD subjects that did not die by suicide, while subjects that did not die by suicide had increased KYAT2 mRNA, which we hypothesise may protect against a decrease in KYNA. Overall, we found sex- and suicide-specific alterations in the KP in the ACC in MDD. This is the first molecular evidence in the brain of subgroup specific changes in the KP in MDD, which not only suggests that treatments aimed at upregulation of the KYNA arm in the brain may be favourable for female MDD sufferers but also might assist managing suicidal behaviour.

Indexed as

Major Depressive DisorderSuicideDepressionFemaleGyrus CinguliHumansKynurenic AcidKynurenineQuinolinic AcidRNA, MessengerKynurenic AcidKynurenineQuinolinic AcidRNA, Messenger

Identifiers

PMID37735504
PMCPMC10789861
OpenAlexW4386929114

What OpenQuestion holds

Textmetadata
LicenceCC BY
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Registered trials

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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.