Evidence map›Paper›PMID 34999196›Full record

ArticleBrain, behavior, and immunity2022

Peripheral and central kynurenine pathway abnormalities in major depression.

Elisabeth R Paul, Lilly Schwieler, Sophie Erhardt, Sandra Boda, Ada Trepci, Robin Kämpe, Anna Asratian, Lovisa Holm, Adam Yngve, Robert Dantzer and 3 more

Open access · hybridAbstract read
In one paragraph

Article in Brain, behavior, and immunity, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers.

0numbers the graph read from it
0cells of the map it votes in
63citing papers in PubMed
6.7field-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

63 citing papers in PubMed, 116 citations in OpenAlex.

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3 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

13 authors at 3 institutions in 2 countries.

Elisabeth R PaulCenter for Social and Affective Neuroscience, Department of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden; Center for Medical Imaging and Visualization, Linköping University, Linköping, Sweden.
Lilly SchwielerDepartment of Physiology and Pharmacology, Karolinska Institute, Stockholm, Sweden.
Sophie ErhardtDepartment of Physiology and Pharmacology, Karolinska Institute, Stockholm, Sweden.
Sandra BodaCenter for Social and Affective Neuroscience, Department of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden; Center for Medical Imaging and Visualization, Linköping University, Linköping, Sweden; Department of Psychiatry, Region Östergötland, Linköping, Sweden.
Ada TrepciDepartment of Physiology and Pharmacology, Karolinska Institute, Stockholm, Sweden.
Robin KämpeCenter for Social and Affective Neuroscience, Department of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden; Center for Medical Imaging and Visualization, Linköping University, Linköping, Sweden.
Anna AsratianCenter for Social and Affective Neuroscience, Department of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden.
Lovisa HolmCenter for Social and Affective Neuroscience, Department of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden.
Adam YngveCenter for Social and Affective Neuroscience, Department of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden; Center for Medical Imaging and Visualization, Linköping University, Linköping, Sweden.
Robert DantzerDepartment of Symptom Research, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Markus HeiligCenter for Social and Affective Neuroscience, Department of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden; Department of Psychiatry, Region Östergötland, Linköping, Sweden.
J Paul HamiltonCenter for Social and Affective Neuroscience, Department of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden; Center for Medical Imaging and Visualization, Linköping University, Linköping, Sweden. Electronic address: paul.hamilton@liu.se.
Martin SamuelssonCenter for Social and Affective Neuroscience, Department of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden; Department of Psychiatry, Region Östergötland, Linköping, Sweden.
Karolinska Institutet · SELinköping University · SEThe University of Texas MD Anderson Cancer Center · US

Funding

Tumor Evolution and Metastasis ProgramP30CA016672 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI DIANE BODURKA · 1985 to 2026
$290.8M
Neuroimmune Mechanisms of Recovery from Comorbid Depression and Chronic PainR01NS073939 · NINDS · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI DANTZER, ROBERT, HEIJNEN, COBI J · 2011 to 2020
$4.0M
The Metabolic Basis of Cancer-Related FatigueR01CA193522 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI DANTZER, ROBERT · 2015 to 2023
$3.8M
NCI NIH HHS P30 CA016672NCI NIH HHS R01 CA193522NINDS NIH HHS R01 NS073939
6 · The paper itself

Abstract

Considerable data relate major depressive disorder (MDD) with aberrant immune system functioning. Pro-inflammatory cytokines facilitate metabolism of tryptophan along the kynurenine pathway (KP) putatively resulting in reduced neuroprotective and increased neurotoxic KP metabolites in MDD, in addition to modulating metabolic and immune function. This central nervous system hypothesis has, however, only been tested in the periphery. Here, we measured KP-metabolite levels in both plasma and cerebrospinal fluid (CSF) of depressed patients (n = 63/36 respectively) and healthy controls (n = 48/33). Further, we assessed the relation between KP abnormalities and brain-structure volumes, as well as body mass index (BMI), an index of metabolic disturbance associated with atypical depression. Plasma levels of picolinic acid (PIC), the kynurenic/quinolinic acid ratio (KYNA/QUIN), and PIC/QUIN were lower in MDD, but QUIN levels were increased. In the CSF, we found lower PIC in MDD. Confirming previous work, MDD patients had lower hippocampal, and amygdalar volumes. Hippocampal and amygdalar volumes were correlated positively with plasma KYNA/QUIN ratio in MDD patients. BMI was increased in the MDD group relative to the control group. Moreover, BMI was inversely correlated with plasma and CSF PIC and PIC/QUIN, and positively correlated with plasma QUIN levels in MDD. Our results partially confirm previous peripheral KP findings and extend them to the CSF in MDD. We present the novel finding that abnormalities in KP metabolites are related to metabolic disturbances in depression, but the relation between KP metabolites and depression-associated brain atrophy might not be as direct as previously hypothesized.

Indexed as

Major Depressive DisorderDepressionHumansKynurenic AcidKynurenineQuinolinic AcidKynurenic AcidKynurenineQuinolinic AcidBrain volumetryCentral nervous systemCerebrospinal fluidInflammationKynurenine pathwayMajor depressive disorderStructural magnetic resonance imaging

Identifiers

PMID34999196
PMCPMC9045681
OpenAlexW4205508152

What OpenQuestion holds

Textmetadata
LicenceTDM
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.