Evidence map›Paper›PMID 40994835›Full record

ArticleBiological psychiatry global open science2025

Epigenetic and Structural Brain Aging and Their Associations With Major Depressive Disorder.

Eileen Y Xu, Claire Green, Daniel L McCartney, Laura K M Han, Kathryn L Evans, Rosie M Walker, Danni A Gadd, Douglas Steele, Gordon Waiter, Archie Campbell and 5 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Biological psychiatry global open science, 2025. 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

15 authors.

Eileen Y XuDivision of Psychiatry, Institute for Neuroscience and Cardiovascular Research, University of Edinburgh, Edinburgh, United Kingdom.
Claire GreenDivision of Psychiatry, Institute for Neuroscience and Cardiovascular Research, University of Edinburgh, Edinburgh, United Kingdom.
Daniel L McCartneyCenter for Genomic and Experimental Medicine, Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, United Kingdom.
Laura K M HanDepartment of Psychiatry, Amsterdam University Medical Center location Vrije Universiteit Amsterdam, Amsterdam, the Netherlands.
Kathryn L EvansCenter for Genomic and Experimental Medicine, Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, United Kingdom.
Rosie M WalkerCenter for Genomic and Experimental Medicine, Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, United Kingdom.
Danni A GaddCenter for Genomic and Experimental Medicine, Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, United Kingdom.
Douglas SteeleSchool of Medicine, University of Dundee, Dundee, United Kingdom.
Gordon WaiterAberdeen Biomedical Imaging Centre, School of Medicine, Medical Sciences and Nutrition, University of Aberdeen, Aberdeen, United Kingdom.
Archie CampbellCenter for Genomic and Experimental Medicine, Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, United Kingdom.
Stephen M LawrieDivision of Psychiatry, Institute for Neuroscience and Cardiovascular Research, University of Edinburgh, Edinburgh, United Kingdom.
James H ColeDementia Research Center, Queen Square Institute of Neurology, University College London, London, United Kingdom.
Andrew M McIntoshDivision of Psychiatry, Institute for Neuroscience and Cardiovascular Research, University of Edinburgh, Edinburgh, United Kingdom.
Xueyi ShenDivision of Psychiatry, Institute for Neuroscience and Cardiovascular Research, University of Edinburgh, Edinburgh, United Kingdom.
Heather C WhalleyDivision of Psychiatry, Institute for Neuroscience and Cardiovascular Research, University of Edinburgh, Edinburgh, United Kingdom.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Background: A growing body of evidence suggests that major depressive disorder (MDD) may be associated with premature biological aging. However, most studies reported to date have examined brain-based (BrainAge) and DNA methylation (DNAm)-based measures (DNAmAge) of biological age (BioAge) in isolation. Methods: We investigated 2 well-studied BioAge measures in lifetime and current MDD: BrainAge and DNAmAge (4 separate DNAmAge measures based on Horvath, Hannum, GrimAge, and PhenoAge clocks). We used cross-sectional cohort data from GS:STRADL (Generation Scotland: STratifying Resilience and Depression Longitudinally) (BrainAge Results: Individuals with lifetime MDD showed significantly higher BrainAge and DNAmAge in GS, ranging from 1.60 to 2.45 years, than individuals without MDD for all measures except for Horvath age. No differences were found for BrainAge in the UKB. In terms of PAD, lifetime MDD was significantly associated with GrimAge-PAD, PhenoAge-PAD, and Brain-PAD, ranging from odds ratio (OR) = 1.21-1.30 (and in UKB, Brain-PAD OR = 1.05). DNAm-PAD and Brain-PAD demonstrated shared and distinctive associations with lifetime MDD, where PhenoAge-PAD plus Brain-PAD explained maximum variance (area under the curve = 0.69, Conclusions: Our findings highlight shared and distinct associations of premature brain and DNAm aging in lifetime MDD.

Indexed as

Biological ageBrain ageDepressionEpigenetic ageMajor depressive disorderMethylation

Identifiers

PMID40994835
PMCPMC12454886

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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.