Evidence map›Paper›PMID 41951638›Full record

ArticleNature communications2026

Astrocyte fatty acid metabolism as a driver of risk for major depressive disorder.

Eamon Fitzgerald, Nicholas O'Toole, Irina Pokhvisneva, Eric J Nestler, Gustavo Turecki, Corina Nagy, Michael J Meaney

Abstract read
In one paragraph

Article in Nature communications, 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. Article
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.

Eamon FitzgeraldDepartment of Psychiatry, Douglas Mental Health University Institute, McGill University, Montréal, QC, Canada. eamon@cervolve.com.ORCID http://orcid.org/0000-0001-9355-7294
Nicholas O'TooleDepartment of Psychiatry, Douglas Mental Health University Institute, McGill University, Montréal, QC, Canada.
Irina PokhvisnevaDepartment of Psychiatry, Douglas Mental Health University Institute, McGill University, Montréal, QC, Canada.
Eric J NestlerNash Family Department of Neuroscience and Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.ORCID http://orcid.org/0000-0002-7905-2000
Gustavo TureckiDepartment of Psychiatry, Douglas Mental Health University Institute, McGill University, Montréal, QC, Canada.ORCID http://orcid.org/0000-0003-4075-2736
Corina NagyDepartment of Psychiatry, Douglas Mental Health University Institute, McGill University, Montréal, QC, Canada.ORCID http://orcid.org/0000-0003-1439-0129
Michael J MeaneyDepartment of Psychiatry, Douglas Mental Health University Institute, McGill University, Montréal, QC, Canada. michael.meaney@mcgill.ca.ORCID http://orcid.org/0000-0002-8605-1997

Funding

Epigenetic Mechanisms of Chronic Stress ActionR01MH129306 · NIMH · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI ERIC J. NESTLER · 2023 to 2026
$2.7M
NIMH NIH HHS R01 MH129306
6 · The paper itself

Abstract

Genome-wide association studies (GWAS) have successfully identified genetic loci associated with major depressive disorder (MDD), yet the complex gene networks underpinning this polygenic risk remain largely uncharacterised. Here, we elucidate the neurobiological mechanisms of MDD by analyzing co-expression networks of 94 risk genes in the human prefrontal cortex. By linking these networks to individual symptoms, we identify the FADS1 (fatty acid desaturase 1) network as a central integrator across symptom clusters. We find that the FADS1 network functions primarily in astrocytes to regulate fatty acid metabolism and influence oligodendrocyte-related cell states. Furthermore, we identify FGF2 as a synaptic effector of this pathway and highlight PPARα (peroxisome proliferator-activated receptor alpha) as a putative therapeutic target. These results establish astrocyte fatty acid metabolism as a critical mechanistic contributor to MDD and a promising avenue for treatment.

Indexed as

AstrocytesFatty Acid DesaturasesFatty AcidsMajor Depressive DisorderDelta-5 Fatty Acid DesaturaseGene Regulatory NetworksGenetic Predisposition to DiseaseGenome-Wide Association StudyHumansOligodendrogliaPolymorphism, Single NucleotidePPAR alphaPrefrontal CortexDelta-5 Fatty Acid DesaturaseFADS1 protein, humanFatty Acid DesaturasesFatty AcidsPPAR alpha

Identifiers

PMID41951638
PMCPMC13237068

What OpenQuestion holds

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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 OpenQuestion graph.