Evidence map›Paper›PMID 41731715›Full record

ArticleActa neuropsychiatrica2026

Peripheral metabolic-redox signaling as a core mechanism of major depressive disorder: evidence from deep metabolomic phenotyping.

Michael Maes, Mengqi Niu, Annabel Maes, Yiping Luo, Chenkai Yangyang, Abbas F Almulla, Jing Li, Yingqian Zhang

Abstract read
In one paragraph

Article in Acta neuropsychiatrica, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
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

1 citing paper in PubMed.

  1. Review
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

8 authors.

Michael MaesInternational NIMETOX Center, Sichuan Provincial Center for Mental Health, Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, China.ORCID https://orcid.org/0000-0002-2012-871X
Mengqi NiuInternational NIMETOX Center, Sichuan Provincial Center for Mental Health, Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, China.
Annabel MaesInternational NIMETOX Center, Sichuan Provincial Center for Mental Health, Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, China.
Yiping LuoInternational NIMETOX Center, Sichuan Provincial Center for Mental Health, Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, China.
Chenkai YangyangKey Laboratory of Psychosomatic Medicine, Chinese Academy of Medical Sciences, Chengdu, China.
Abbas F AlmullaKey Laboratory of Psychosomatic Medicine, Chinese Academy of Medical Sciences, Chengdu, China.ORCID https://orcid.org/0000-0002-7667-6731
Jing LiKey Laboratory of Psychosomatic Medicine, Chinese Academy of Medical Sciences, Chengdu, China.
Yingqian ZhangUniversity of Electronic Science and Technology of Chinahttps://ror.org/04qr3zq92, Chengdu, China.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundMajor depressive disorder (MDD) is a neuro-immune, oxidative, and nitrosative stress (NIMETOX) disorder, in which peripheral immune-redox pathways intersect with metabolic networks leading to neurotoxicity within the limbic-prefrontal affective circuits. Comprehensive metabolomics analysis in well-phenotyped patients is vital to elucidate their metabolic profile.

objectivesTo identify metabolic abnormalities that differentiate in patients with severe MDD from healthy controls(HCs) through high-resolution, untargeted metabolomics.

methodsSerum samples from 125 MDD inpatients and 40 HCs were analyzed utilizing liquid chromatography(LC) and mass spectrometry(MS). A meticulously regulated multistage machine-learning pipeline with leakage-prevention protocols was employed to analyze differences between MDD and controls and to predict phenome scores.

resultsFeature selection showed that 16 metabolites and 6 functional modules reliably distinguished MDD. The functional profile of the metabolites indicates a convergence of lipotoxicity, phospholipid(PL) remodeling, disruptions in fatty acid(FA) metabolism, mitochondrial redox imbalance, ether-lipid metabolism, and antioxidant depletion. This MDD metabotype was not affected by metabolic syndrome(MetS). A substantial portion of the variance in overall depression severity (72.5%), physiosomatic symptoms (55.8%), and suicidal ideation(SI) (23.6%) was accounted for by increased lipotoxicity, PL remodeling, and FA storage/signaling. The recurrence of illness (27.7%) was associated with a self-reinforcing lipid-redox-inflammatory module that maintains cellular stress. DISCUSSION: The MDD metabotype represents a cohesive metabolic network that is associated with the NIMETOX pathogenesis of MDD. Metabolomics provides a comprehensive foundation for subtyping and precision psychiatry. Lipoxygenase-15, lipotoxicity, phospholipase A

Indexed as

Major Depressive DisorderMetabolomicsAdultFemaleHumansLipid MetabolismMaleMetabolomeMiddle AgedOxidation-ReductionOxidative StressPhenotypeSignal Transductionantioxidantslipidsmetabolismneuro-immunenomothetic precision psychiatryoxidative and nitrosative stress

Identifiers

PMID41731715
PMCPMC13130358

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
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 Socratic graph.