Evidence map›Paper›PMID 26122586›Full record

SynthesisMolecular psychiatry2016

Subcortical brain alterations in major depressive disorder: findings from the ENIGMA Major Depressive Disorder working group.

L Schmaal, D J Veltman, T G M van Erp, P G Sämann, T Frodl, N Jahanshad, E Loehrer, H Tiemeier, A Hofman, W J Niessen and 52 more

2 registry-linked trialsAbstract readMeta-Analysis
PubMed Full text at PMC Publisher
In one paragraph

Synthesis in Molecular psychiatry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 588 papers, 12 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
588citing papers in PubMed, 12 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.

NCT03779477 nacompletednot on this mapstarted 2018, after this paper: background citation

Effect of "Coping With Stress Program" to Depression and Anxiety Symptoms and Brain Functions in Adolescent at High-Risk for Depression

TypeinterventionalSponsorDokuz Eylul UniversityRan2018 to 2020Enrolled57ConditionsDepressionArmsCoping with Stress Course
NCT05034523 unknown statusnot on this mapstarted 2021, after this paper: background citation

Voxel Based Morphometry In Patients With Psychotic Versus Non Psychotic Depression

TypeobservationalSponsorAssiut UniversityRan2021 to 2022Enrolled66ConditionsPsychotic Depression, Non Psychotic DepressionArmsMRI Voxel based morphometry
3 · Its place in the literature

Who cites it

588 citing papers in PubMed, 12 syntheses or guidelines pooled it.

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  20. The neuroanatomy of depression: weak but replicable effects in 4021 individuals from three clinical cohorts.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026
    Article

528 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

62 authors.

L SchmaalDepartment of Psychiatry and Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, The Netherlands.
D J VeltmanDepartment of Psychiatry and Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, The Netherlands.
T G M van ErpDepartment of Psychiatry and Human Behavior, University of California, Irvine, CA, USA.
P G SämannMax Planck Institute of Psychiatry, Munich, Germany.
T FrodlDepartment of Psychiatry, University of Regensburg, Regensburg, Germany.
N JahanshadImaging Genetics Center, Department of Neurology, Keck School of Medicine, University of Southern California, Marina del Rey, CA, USA.
E LoehrerDepartment of Epidemiology, Erasmus MC University Medical Center, Rotterdam, The Netherlands.
H TiemeierDepartment of Epidemiology, Erasmus MC University Medical Center, Rotterdam, The Netherlands.ORCID 0000-0002-4395-1397
A HofmanDepartment of Epidemiology, Erasmus MC University Medical Center, Rotterdam, The Netherlands.
W J NiessenDepartments of Radiology and Medical Informatics, Erasmus MC University Medical Center, Rotterdam, The Netherlands.
M W VernooijDepartment of Epidemiology, Erasmus MC University Medical Center, Rotterdam, The Netherlands.
M A IkramDepartment of Epidemiology, Erasmus MC University Medical Center, Rotterdam, The Netherlands.
K WittfeldGerman Center for Neurodegenerative Diseases (DZNE), Rostock/Greifswald, Germany.
H J GrabeGerman Center for Neurodegenerative Diseases (DZNE), Rostock/Greifswald, Germany.
A BlockDepartment of Psychiatry and Psychotherapy, University Medicine Greifswald, Greifswald, Germany.
K HegenscheidInstitute of Diagnostic Radiology and Neuroradiology, University Medicine Greifswald, Greifswald, Germany.
H VölzkeInstitute for Community Medicine, University Medicine Greifswald, Greifswald, Germany.
D HoehnMax Planck Institute of Psychiatry, Munich, Germany.
M CzischMax Planck Institute of Psychiatry, Munich, Germany.
J LagopoulosClinical Research Unit, Brain and Mind Research Institute, University of Sydney, Camperdown, Australia.
S N HattonClinical Research Unit, Brain and Mind Research Institute, University of Sydney, Camperdown, Australia.
I B HickieClinical Research Unit, Brain and Mind Research Institute, University of Sydney, Camperdown, Australia.
R Goya-MaldonadoCenter for Translational Research in Systems Neuroscience and Psychiatry, Department of Psychiatry and Psychotherapy, University Medical Center, Goettingen, Germany.
B KrämerCenter for Translational Research in Systems Neuroscience and Psychiatry, Department of Psychiatry and Psychotherapy, University Medical Center, Goettingen, Germany.
O GruberCenter for Translational Research in Systems Neuroscience and Psychiatry, Department of Psychiatry and Psychotherapy, University Medical Center, Goettingen, Germany.
B Couvy-DuchesneNeuroImaging Genetics, QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia.
M E RenteríaGenetic Epidemiology, QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia.
L T StrikeNeuroImaging Genetics, QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia.
N T MillsGenetic Epidemiology, QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia.
G I de ZubicaraySchool of Psychology, University of Queensland, Brisbane, QLD, Australia.
K L McMahonCenter for Advanced Imaging, University of Queensland, Brisbane, QLD, Australia.
S E MedlandQuantitative Genetics, QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia.
N G MartinGenetic Epidemiology, QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia.
N A GillespieVirginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond, VA, USA.
M J WrightNeuroImaging Genetics, QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia.
G B HallDepartment of Psychology, Neuroscience and Behaviour, McMaster University, Hamilton, ON, Canada.
G M MacQueenDepartment of Psychiatry, Mathison Centre for Mental Health Research and Education, Hotchkiss Brain Institute, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada.
E M FreyDepartment of Psychiatry, University of Regensburg, Regensburg, Germany.
A CarballedoDepartment of Psychiatry and Institute of Neuroscience, University of Dublin, Trinity College Dublin, Dublin, Ireland.
L S van VelzenDepartment of Psychiatry and Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, The Netherlands.
M J van TolUniversity of Groningen, University Medical Center Groningen, NeuroImaging Center, Groningen, The Netherlands.
N J van der WeeDepartment of Psychiatry, Leiden University Medical Center, Leiden University, Leiden, The Netherlands.
I M VeerDepartment of Psychiatry and Psychotherapy, Division of Mind and Brain Research, Charité Universitätsmedizin Berlin, Berlin, Germany.
H WalterDepartment of Psychiatry and Psychotherapy, Division of Mind and Brain Research, Charité Universitätsmedizin Berlin, Berlin, Germany.
K SchnellDepartment of General Psychiatry, University Hospital Heidelberg, Heidelberg, Germany.
E SchrammDepartment of Psychiatry and Psychotherapy, University Medical Center Freiburg, Freiburg im Breisgau, Germany.
C NormannDepartment of Psychiatry and Psychotherapy, University Medical Center Freiburg, Freiburg im Breisgau, Germany.
D SchoepfDepartment of Psychiatry, University of Bonn, Bonn, Germany.
C KonradDepartment of Psychiatry and Psychotherapy, Philipps-University Marburg, Marburg, Germany.
B ZurowskiCenter for Integrative Psychiatry, University of Lübeck, Lübeck, Germany.
T NicksonDivision of Psychiatry, University of Edinburgh, Edinburgh, UK.
A M McIntoshDivision of Psychiatry, University of Edinburgh, Edinburgh, UK.
M PapmeyerDivision of Psychiatry, University of Edinburgh, Edinburgh, UK.
H C WhalleyDivision of Psychiatry, University of Edinburgh, Edinburgh, UK.
J E SussmannDivision of Psychiatry, University of Edinburgh, Edinburgh, UK.
B R GodlewskaUniversity Department of Psychiatry, Warneford Hospital, Oxford, UK.
P J CowenUniversity Department of Psychiatry, Warneford Hospital, Oxford, UK.
F H FischerDepartment of Psychosomatic Medicine, Center for Internal Medicine and Dermatology, Charité Universitätsmedizin, Berlin, Germany.
M RoseDepartment of Psychosomatic Medicine, Center for Internal Medicine and Dermatology, Charité Universitätsmedizin, Berlin, Germany.
B W J H PenninxDepartment of Psychiatry and Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, The Netherlands.
P M ThompsonImaging Genetics Center, Department of Neurology, Keck School of Medicine, University of Southern California, Marina del Rey, CA, USA.
D P HibarImaging Genetics Center, Department of Neurology, Keck School of Medicine, University of Southern California, Marina del Rey, CA, USA.

Funding

TR&D3: Intrinsic Surface MappingP41EB015922 · NIBIB · UNIVERSITY OF SOUTHERN CALIFORNIA · PI VAN HORN, JOHN DARRELL · 2012 to 2022
$14.1M
TrainingU54EB020406 · NIBIB · UNIVERSITY OF SOUTHERN CALIFORNIA · PI TOGA, ARTHUR W · 2014 to 2018
$12.5M
Training U54EB020403 · NIBIB · UNIVERSITY OF SOUTHERN CALIFORNIA · PI THOMPSON, PAUL M · 2014 to 2018
$10.1M
Genetic influences on the brain: A twin imaging studyR01HD050735 · NICHD · QUEENSLAND INSTITUTE OF MEDICAL RESEARCH · PI WRIGHT, MARGARET JANE · 2007 to 2011
$2.6M
Genetic & environmental pathways to drug use, abuse & dependenceR00DA023549 · NIDA · VIRGINIA COMMONWEALTH UNIVERSITY · PI GILLESPIE, NATHAN ALEXANDER · 2010 to 2012
$717k
Chief Scientist Office SCD/12Medical Research Council G0701421Medical Research Council MR/K022202/1Medical Research Council MR/K026992/1NIBIB NIH HHS U54 EB020406NICHD NIH HHS R01 HD050735NIDA NIH HHS R00 DA023549Wellcome Trust 104036
6 · The paper itself

Abstract

The pattern of structural brain alterations associated with major depressive disorder (MDD) remains unresolved. This is in part due to small sample sizes of neuroimaging studies resulting in limited statistical power, disease heterogeneity and the complex interactions between clinical characteristics and brain morphology. To address this, we meta-analyzed three-dimensional brain magnetic resonance imaging data from 1728 MDD patients and 7199 controls from 15 research samples worldwide, to identify subcortical brain volumes that robustly discriminate MDD patients from healthy controls. Relative to controls, patients had significantly lower hippocampal volumes (Cohen's d=-0.14, % difference=-1.24). This effect was driven by patients with recurrent MDD (Cohen's d=-0.17, % difference=-1.44), and we detected no differences between first episode patients and controls. Age of onset ⩽21 was associated with a smaller hippocampus (Cohen's d=-0.20, % difference=-1.85) and a trend toward smaller amygdala (Cohen's d=-0.11, % difference=-1.23) and larger lateral ventricles (Cohen's d=0.12, % difference=5.11). Symptom severity at study inclusion was not associated with any regional brain volumes. Sample characteristics such as mean age, proportion of antidepressant users and proportion of remitted patients, and methodological characteristics did not significantly moderate alterations in brain volumes in MDD. Samples with a higher proportion of antipsychotic medication users showed larger caudate volumes in MDD patients compared with controls. This currently largest worldwide effort to identify subcortical brain alterations showed robust smaller hippocampal volumes in MDD patients, moderated by age of onset and first episode versus recurrent episode status.

Indexed as

AdultBrainCase-Control StudiesFemaleHippocampusHumansMagnetic Resonance ImagingMajor Depressive DisorderMaleMiddle AgedNeuroimaging

Identifiers

PMID26122586
PMCPMC4879183

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Registered trials

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.