Evidence map›Paper›PMID 41258534›Full record

ArticleCommunications medicine2025

Neuroanatomical dimensions in major depression linked to cognition, adverse life events, self-harm, metabolomics and genetics.

Wenyi Xiao, Rachel D Woodham, Yuhan Cui, Junhao Wen, Mathilde Antoniades, Dhivya Srinivasan, Yong Fan, Guray Erus, Jose A Garcia, Stephen R Arnott and 40 more

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In one paragraph

Article in Communications medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed, 1 pooled it
–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

2 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. 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

50 authors.

Wenyi Xiao *School of Childhood and Social Care, University of East London, London, UK. w.xiao@uel.ac.uk.ORCID http://orcid.org/0009-0005-3387-1173
Rachel D Woodham *School of Childhood and Social Care, University of East London, London, UK. r.woodham@uel.ac.uk.ORCID http://orcid.org/0000-0002-5581-9449
Yuhan Cui *Center for Biomedical Image Computing and Analytics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Junhao WenCenter for Biomedical Image Computing and Analytics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Mathilde AntoniadesCenter for Biomedical Image Computing and Analytics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.ORCID http://orcid.org/0000-0002-8241-835X
Dhivya SrinivasanCenter for Biomedical Image Computing and Analytics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Yong FanCenter for Biomedical Image Computing and Analytics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.ORCID http://orcid.org/0000-0001-9869-4685
Guray ErusCenter for Biomedical Image Computing and Analytics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.ORCID http://orcid.org/0000-0001-6633-4861
Jose A GarciaCenter for Biomedical Image Computing and Analytics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.ORCID http://orcid.org/0009-0000-2703-0777
Stephen R ArnottRotman Research Institute, Baycrest Centre, Ontario, ON, Canada.ORCID http://orcid.org/0000-0002-0616-7771
Taolin ChenDepartment of Radiology, Huaxi MR Research Center (HMRRC), Institute of Radiology, Functional and Molecular Imaging Key Laboratory of Sichuan Province, West China Hospital of Sichuan University, Chengdu, Sichuan, China.
Ki Sueng ChoiNash Family Center for Advanced Circuit Therapeutics, Icahn School of Medicine at Mount Sinai, New York, NY, USA.ORCID http://orcid.org/0000-0002-6446-0677
Cherise Chin FattDepartment of Psychiatry, Center for Depression Research and Clinical Care, University of Texas Southwestern Medical Center, Dallas, TX, USA.ORCID http://orcid.org/0000-0001-5080-6799
Benicio N FreyDepartment of Psychiatry and Behavioural Neurosciences, McMaster University, Ontario, ON, Canada.ORCID http://orcid.org/0000-0001-8267-943X
Vibe G FrokjaerNeurobiology Research Unit, University Hospital Rigshospitalet, Copenhagen, Denmark.
Melanie GanzNeurobiology Research Unit, University Hospital Rigshospitalet, Copenhagen, Denmark.ORCID http://orcid.org/0000-0002-9120-8098
Beata R GodlewskaDepartment of Psychiatry, University of Oxford, Oxford, UK.ORCID http://orcid.org/0000-0002-5973-3765
Stefanie HasselMathison Centre for Mental Health Research and Education, University of Calgary, Calgary, AB, Canada.
Keith HoDepartment of Psychiatry, University Health Network, Ontario, ON, Canada.
Andrew M McIntoshDivision of Psychiatry, Centre for Clinical Brain Sciences, Royal Infirmary Edinburgh, Edinburgh, UK.ORCID http://orcid.org/0000-0002-0198-4588
Kun QinDepartment of Radiology, Huaxi MR Research Center (HMRRC), Institute of Radiology, Functional and Molecular Imaging Key Laboratory of Sichuan Province, West China Hospital of Sichuan University, Chengdu, Sichuan, China.ORCID http://orcid.org/0000-0003-1254-6388
Susan RotzingerDepartment of Psychiatry, University Health Network, Ontario, ON, Canada.
Matthew D SacchetMeditation Research Program, Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Jonathan SavitzLaureate Institute for Brain Research, Tulsa, OK, USA.ORCID http://orcid.org/0000-0001-8143-182X
Haochang ShouCenter for Biomedical Image Computing and Analytics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.ORCID http://orcid.org/0000-0002-3043-047X
Ashish SinghCenter for Biomedical Image Computing and Analytics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.ORCID http://orcid.org/0000-0003-4486-3636
Aleks StolicynDivision of Psychiatry, Centre for Clinical Brain Sciences, Royal Infirmary Edinburgh, Edinburgh, UK.ORCID http://orcid.org/0000-0002-1147-7539
Irina StrigoDepartment of Psychiatry, University of California San Francisco, San Francisco, CA, USA.ORCID http://orcid.org/0000-0002-8799-716X
Stephen C StrotherRotman Research Institute, Baycrest Centre, Ontario, ON, Canada.ORCID http://orcid.org/0000-0002-3198-217X
Duygu TosunDepartment of Radiology and Biomedical Imaging, University of California San Francisco, San Francisco, CA, USA.ORCID http://orcid.org/0000-0001-8644-7724
Dongtao WeiSchool of Psychology, Southwest University, Chongqing, China.
Ian M AndersonDivision of Neuroscience and Experimental Psychology, University of Manchester, Manchester, UK.
W Edward CraigheadDepartment of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA, USA.ORCID http://orcid.org/0000-0001-9957-0027
J F William DeakinDivision of Neuroscience and Experimental Psychology, University of Manchester, Manchester, UK.ORCID http://orcid.org/0000-0002-2750-962X
Boadie W DunlopDepartment of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA, USA.ORCID http://orcid.org/0000-0002-4653-0483
Rebecca ElliottDivision of Neuroscience and Experimental Psychology, University of Manchester, Manchester, UK.ORCID http://orcid.org/0000-0002-7602-010X
Qiyong GongDepartment of Radiology, Huaxi MR Research Center (HMRRC), Institute of Radiology, Functional and Molecular Imaging Key Laboratory of Sichuan Province, West China Hospital of Sichuan University, Chengdu, Sichuan, China.ORCID http://orcid.org/0000-0002-5912-4871
Ian H GotlibDepartment of Psychology, Stanford University, Stanford, CA, USA.
Catherine J HarmerDepartment of Psychiatry, University of Oxford, Oxford, UK.ORCID http://orcid.org/0000-0002-1609-8335
Sidney H KennedyDepartment of Psychiatry, University Health Network, Ontario, ON, Canada.ORCID http://orcid.org/0000-0001-5339-7185
Gitte M KnudsenNeurobiology Research Unit, University Hospital Rigshospitalet, Copenhagen, Denmark.ORCID http://orcid.org/0000-0003-1508-6866
Helen S MaybergNash Family Center for Advanced Circuit Therapeutics, Icahn School of Medicine at Mount Sinai, New York, NY, USA.ORCID http://orcid.org/0000-0002-1672-2716
Martin P PaulusLaureate Institute for Brain Research, Tulsa, OK, USA.ORCID http://orcid.org/0000-0002-0825-3606
Jiang QiuSchool of Psychology, Southwest University, Chongqing, China.
Madhukar H TrivediDepartment of Psychiatry, Center for Depression Research and Clinical Care, University of Texas Southwestern Medical Center, Dallas, TX, USA.ORCID http://orcid.org/0000-0002-2983-1110
Heather C WhalleyDivision of Psychiatry, Centre for Clinical Brain Sciences, Royal Infirmary Edinburgh, Edinburgh, UK.ORCID http://orcid.org/0000-0002-4505-8869
Chao-Gan YanDepartment of Psychological and Cognitive Sciences, Tsinghua University, Beijing, China.ORCID http://orcid.org/0000-0003-3413-5977
Allan H YoungCentre for Affective Disorders, Department of Psychological Medicine, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
Christos DavatzikosCenter for Biomedical Image Computing and Analytics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.ORCID http://orcid.org/0000-0002-1025-8561
Cynthia H Y FuSchool of Childhood and Social Care, University of East London, London, UK. c.fu@uel.ac.uk.ORCID http://orcid.org/0000-0003-4313-3500

Funding

Disentangling the anatomical, functional and clinical heterogeneity of major depression, using machine learning methodsR01MH134236 · NIMH · UNIVERSITY OF PENNSYLVANIA · PI DAVATZIKOS, CHRISTOS, FU, CYNTHIA · 2023 to 2024
$1.5M
Disentangling the anatomical, functional and clinical heterogeneity of major depression, using machine learning methodsRF1MH134236 · NIMH · UNIVERSITY OF PENNSYLVANIA · PI DAVATZIKOS, CHRISTOS · 2025 to 2025
$1.4M
CSRD VA IK6 CX002926NIMH NIH HHS R01 MH134236NIMH NIH HHS RF1 MH134236
6 · The paper itself

Abstract

backgroundMajor depressive disorder (MDD) is a leading cause of disability worldwide, yet its diagnosis relies on clinical symptoms alone.

methodsUsing the semi-supervised machine learning algorithm, Heterogeneity through Discriminative Analysis (HYDRA), we had identified two neuroanatomical dimensions in deeply phenotyped (i.e., comprehensively assessed across neuroimaging, clinical, and behavioural domains), medication-free participants with MDD from the COORDINATE-MDD consortium. In the present study, we apply this pre-trained HYDRA model to the UK Biobank (UKB) to validate these dimensions in a large general population and a subsample with current depressive symptoms.

resultsDimension 2 (D2), compared to Dimension 1 (D1), is characterized by reduced grey and white matter volumes and limited treatment response to antidepressant and placebo medications. Out-of-sample validation in the UKB general population (n = 37,235) confirms these neuroanatomical features and reveals D2 associations with cognitive impairments, adverse life events, self-harm and suicide attempts, a pro-atherogenic lipid profile, and genetic links to neurodegenerative traits. Similar profiles are observed in the UKB subsample with current depressive symptoms (n = 1455).

conclusionsD1 and D2 represent distinct neurobiological mechanisms underlying MDD. The validation in a general population-based cohort and in a cohort sample with depressive symptoms delineates mechanisms underlying heterogeneity in MDD.

Identifiers

PMID41258534
PMCPMC12663290

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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.