Evidence map›Paper›PMID 38273283›Full record

ArticleBMC medicine2024

Dysfunction in endocannabinoids, palmitoylethanolamide, and degradation of tryptophan into kynurenine in individuals with depressive symptoms.

Stefano Comai, Nicolas Nunez, Tobias Atkin, Maykel F Ghabrash, Rita Zakarian, Allan Fielding, Marie Saint-Laurent, Nancy Low, Garrett Sauber, Eugenio Ragazzi and 2 more

Open access · goldAbstract read
In one paragraph

Article in BMC medicine, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
2.0field-weighted citation impact, top 13% 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

4 citing papers in PubMed, 13 citations in OpenAlex.

  1. Article
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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

12 authors at 4 institutions in 3 countries.

Stefano ComaiDepartment of Pharmaceutical and Pharmacological Sciences, University of Padua, Padua, Italy. stefano.comai@unipd.it.
Nicolas NunezDepartment of Psychiatry, McGill University, Montreal, QC, Canada.
Tobias AtkinDepartment of Psychiatry, McGill University, Montreal, QC, Canada.
Maykel F GhabrashDepartment of Psychiatry, McGill University, Montreal, QC, Canada.
Rita ZakarianDepartment of Psychiatry, McGill University, Montreal, QC, Canada.
Allan FieldingDepartment of Psychiatry, McGill University Health Center, Montreal, QC, Canada.
Marie Saint-LaurentDepartment of Psychiatry, McGill University Health Center, Montreal, QC, Canada.
Nancy LowDepartment of Psychiatry, McGill University, Montreal, QC, Canada.
Garrett SauberNeuroscience Research Center and Department of Pharmacology and Toxicology, Medical College of Wisconsin, Milwaukee, WI, USA.
Eugenio RagazziDepartment of Pharmaceutical and Pharmacological Sciences, University of Padua, Padua, Italy.
Cecilia J HillardNeuroscience Research Center and Department of Pharmacology and Toxicology, Medical College of Wisconsin, Milwaukee, WI, USA.
Gabriella GobbiDepartment of Psychiatry, McGill University, Montreal, QC, Canada. gabriella.gobbi@mcgill.ca.ORCID 0000-0003-4124-9825
McGill University · CAMcGill University Health Centre · CAMedical College of Wisconsin · USUniversity of Padua · IT

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundThe endocannabinoid (eCB) system and the serotonin (5-HT) are both implicated in the severity of the depression. 5-HT is synthesized from the amino acid tryptophan (Trp), which is also a precursor for kynurenine (Kyn) whose production is increased at the expense of 5-HT in depressed patients. No clinical studies have investigated the crosstalk between the eCB system and the Trp/5-HT/Kyn pathways. Here, we hypothesized that the eCB system is associated with an enhanced Kyn production in relation to the severity of depressive symptoms.

methodsEighty-two subjects (51 patients with a diagnosis of depressive disorder (DSM-5) and 31 healthy volunteers), were assessed with the Montgomery-Åsberg Depression Rating Scale (MADRS), Beck Depression Scale, and Global Clinical Impression. Serum concentrations of eCBs (N-arachidonoylethanolamine (AEA) and 2-arachidonoylglycerol (2-AG)); structurally related fatty acyl compounds 2-oleoylglycerol (2-OG), oleoylethanolamide (OEA), and palmitoylethanolamide (PEA); Trp, Kyn, Kyn/Trp ratio (an index of Trp degradation into Kyn) and 5-HT were also determined.

resultsFollowing a principal component analysis including the severity of depression, Kyn and the Kyn/Trp ratio appear to be directly associated with 2-AG, AEA, and PEA. Interestingly, these biomarkers also permitted to distinguish the population into two main clusters: one of individuals having mild/severe depressive symptoms and the other with an absence of depressive symptoms. Using parametric analysis, higher serum levels of 2-AG, Kyn, and the ratio Kyn/Trp and lower levels of Trp and 5-HT were found in individuals with mild/severe depressive symptoms than in those without depressive symptoms. While in asymptomatic people, PEA was directly associated to Trp, and OEA indirectly linked to 5-HT, in individuals with depressive symptoms, these correlations were lost, and instead, positive correlations between AEA and 2-AG, PEA and AEA, and PEA vs 2-AG and OEA concentrations were found.

conclusionsParametric and non-parametric analyses suggest a possible association between eCBs, tryptophan/kynurenine biomarkers, and severity of depression, confirming a likely interplay among inflammation, stress, and depression. The enhanced relationships among the biomarkers of the 2-AG and AEA pathways and related lipids seen in individuals with depressive symptoms, but not in asymptomatics, suggest an altered metabolism of the eCB system in depression.

Indexed as

AmidesEthanolaminesKynureninePalmitic AcidsTryptophanBiomarkersDepressionEndocannabinoidsHumansSerotoninAmidesBiomarkersEndocannabinoidsEthanolaminesKynureninepalmidrolPalmitic AcidsSerotoninTryptophanBiomarkersDepressionEndocannabinoidsKynurenine pathwaySerotonin

Identifiers

PMID38273283
PMCPMC10809514
OpenAlexW4391226711

What OpenQuestion holds

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LicenceCC BY
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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.