Evidence map›Paper›PMID 27483383›Full record

ArticleTranslational psychiatry2016

An enzyme in the kynurenine pathway that governs vulnerability to suicidal behavior by regulating excitotoxicity and neuroinflammation.

L Brundin, C M Sellgren, C K Lim, J Grit, E Pålsson, M Landén, M Samuelsson, K Lundgren, P Brundin, D Fuchs and 4 more

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

Article in Translational psychiatry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 107 papers, 8 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
107citing papers in PubMed, 8 pooled it
5.4field-weighted citation impact, top 2% 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

107 citing papers in PubMed, 8 syntheses or guidelines pooled it, 189 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Pooled it
  4. Pooled it
  5. Pooled it
  6. Pooled it
  7. Pooled it
  8. BrainFrontiers in immunology · 2021
    Pooled it
  9. Trial
  10. Article
  11. Article
  12. Review
  13. Review
  14. Review
  15. Article
  16. Article
  17. Article
  18. Article
  19. Review
  20. Article

47 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

14 authors at 8 institutions in 4 countries.

L BrundinCenter for Neurodegenerative Science, Van Andel Research Institute, Grand Rapids, MI, USA.
C M SellgrenDepartment of Physiology and Pharmacology, Karolinska Institute, Stockholm, Sweden.
C K LimFaculty of Medicine and Health Sciences Macquarie University, Sydney, NSW, Australia.
J GritCenter for Neurodegenerative Science, Van Andel Research Institute, Grand Rapids, MI, USA.
E PålssonInstitute of Neuroscience and Physiology, The Sahlgrenska Academy at Gothenburg University, Gothenburg, Sweden.
M LandénInstitute of Neuroscience and Physiology, The Sahlgrenska Academy at Gothenburg University, Gothenburg, Sweden.
M SamuelssonDepartment of Physiology and Pharmacology, Karolinska Institute, Stockholm, Sweden.
K LundgrenDepartment of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
P BrundinCenter for Neurodegenerative Science, Van Andel Research Institute, Grand Rapids, MI, USA.
D FuchsDivision of Biological Chemistry, Innsbruck Medical University, Center for Chemistry and Biomedicine, Innsbruck, Austria.
T T PostolacheDepartment of Psychiatry, University of Maryland School of Medicine, Baltimore, MD, USA.
L Traskman-BendzSection for Psychiatry, Department of Clinical Sciences, Lund University, Lund, Sweden.
G J GuilleminFaculty of Medicine and Health Sciences Macquarie University, Sydney, NSW, Australia.
S ErhardtDepartment of Physiology and Pharmacology, Karolinska Institute, Stockholm, Sweden.
Van Andel Institute · USKarolinska Institutet · SELinköping University · SEMacquarie University · AUUniversity of Gothenburg · SEInnsbruck Medical University · ATLund University · SEUniversity of Maryland, Baltimore · US

Funding

Role of Kynurenine Pathway Metabolites in Perinatal Depression and SuicidalityR01MH104622 · NIMH · VAN ANDEL RESEARCH INSTITUTE · PI BRUNDIN, LENA CECILIA · 2014 to 2016
$1.2M
CSRD VA I01 CX001310NIMH NIH HHS R01 MH104622
6 · The paper itself

Abstract

Emerging evidence suggests that inflammation has a key role in depression and suicidal behavior. The kynurenine pathway is involved in neuroinflammation and regulates glutamate neurotransmission. In the cerebrospinal fluid (CSF) of suicidal patients, levels of inflammatory cytokines and the kynurenine metabolite quinolinic acid (QUIN), an N-methyl-d-aspartate receptor agonist, are increased. The enzyme amino-β-carboxymuconate-semialdehyde-decarboxylase (ACMSD) limits QUIN formation by competitive production of the neuroprotective metabolite picolinic acid (PIC). Therefore, decreased ACMSD activity can lead to excess QUIN. We tested the hypothesis that deficient ACMSD activity underlies suicidal behavior. We measured PIC and QUIN in CSF and plasma samples from 137 patients exhibiting suicidal behavior and 71 healthy controls. We used DSM-IV and the Montgomery-Åsberg Depression Rating Scale and Suicide Assessment Scale to assess behavioral changes. Finally, we genotyped ACMSD tag single-nucleotide polymorphisms (SNPs) in 77 of the patients and 150 population-based controls. Suicide attempters had reduced PIC and a decreased PIC/QUIN ratio in both CSF (P<0.001) and blood (P=0.001 and P<0.01, respectively). The reductions of PIC in CSF were sustained over 2 years after the suicide attempt based on repeated measures. The minor C allele of the ACMSD SNP rs2121337 was more prevalent in suicide attempters and associated with increased CSF QUIN. Taken together, our data suggest that increased QUIN levels may result from reduced activity of ACMSD in suicidal subjects. We conclude that measures of kynurenine metabolites can be explored as biomarkers of suicide risk, and that ACMSD is a potential therapeutic target in suicidal behavior.

Indexed as

Suicidal IdeationSuicide, AttemptedAdolescentAdultAgedAllelesCarboxy-LyasesCase-Control StudiesChildFemaleHumansInflammationKynurenineMaleMiddle AgedPicolinic Acidsaminocarboxymuconate-semialdehyde decarboxylaseCarboxy-LyasesKynureninepicolinic acidPicolinic AcidsQuinolinic Acid

Identifiers

PMID27483383
PMCPMC5022080
OpenAlexW2504229998

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.