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; M W Vernooij; M A Ikram; K Wittfeld; H J Grabe; A Block; K Hegenscheid; H Völzke; D Hoehn; M Czisch; Jim Lagopoulos; S N Hatton; I B Hickie; R Goya-Maldonado; B Krämer; O Gruber; B Couvy-Duchesne; M E Rentería; L T Strike; N T Mills; G I de Zubicaray; K L McMahon; S E Medland; N G Martin; N A Gillespie; M J Wright; G B Hall; G M MacQueen; E M Frey; A Carballedo; L S van Velzen; M J van Tol; N J van der Wee; I M Veer; H Walter; K Schnell; E Schramm; C Normann; D Schoepf; C Konrad; B Zurowski; T Nickson; M Papmeyer; A M McIntosh; H C Whalley; J E Sussmann; B R Godlewska; P J Cowen; F H Fischer; P M Thompson; M Rose; D P Hibar; B W J H Penninx

doi:10.1038/mp.2015.69

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

Journal article

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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, …

Molecular Psychiatry, Vol.21, pp.806-812

2016

DOI: https://doi.org/10.1038/mp.2015.69

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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.

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Title: Subcortical brain alterations in major depressive disorder: findings from the ENIGMA Major Depressive Disorder working group
Authors: L Schmaal (Author) - VU University Medical Centre, Netherlands
D J Veltman (Author) - VU University Medical Centre, Netherlands
T G M van Erp (Author) - University of California, United States
P G Sämann (Author) - Max Planck Institute of Psychiatry, Germany
T Frodl (Author) - University of Regensburg, Germany
N Jahanshad (Author) - University of Southern California, United States
E Loehrer (Author) - Erasmus MC University Medical Center, Netherlands
H Tiemeier (Author) - Erasmus MC University Medical Center, Netherlands
A Hofman (Author) - Erasmus MC University Medical Center, Netherlands
W J Niessen (Author) - Erasmus MC University Medical Center, Netherlands
M W Vernooij (Author) - Erasmus MC University Medical Center, Netherlands
M A Ikram (Author) - Erasmus MC University Medical Center, Netherlands
K Wittfeld (Author) - German Center for Neurodegenerative Diseases (DZNE), Germany
H J Grabe (Author) - German Center for Neurodegenerative Diseases (DZNE), Germany
A Block (Author) - University Medicine Greifswald, Germany
K Hegenscheid (Author) - University Medicine Greifswald, Germany
H Völzke (Author) - University Medicine Greifswald, Germany
D Hoehn (Author) - Max Planck Institute of Psychiatry, Germany
M Czisch (Author) - Max Planck Institute of Psychiatry, Germany
Jim Lagopoulos (Author) - University of Sydney
S N Hatton (Author) - University of Sydney
I B Hickie (Author) - University of Sydney
R Goya-Maldonado (Author) - University Medical Center, Germany
B Krämer (Author) - University Medical Center, Germany
O Gruber (Author) - University Medical Center, Germany
B Couvy-Duchesne (Author) - University of Queensland
M E Rentería (Author) - QIMR Berghofer Medical Research Institute
L T Strike (Author) - University of Queensland
N T Mills (Author) - University of Queensland
G I de Zubicaray (Author) - University of Queensland
K L McMahon (Author) - University of Queensland
S E Medland (Author) - QIMR Berghofer Medical Research Institute
N G Martin (Author) - QIMR Berghofer Medical Research Institute
N A Gillespie (Author) - Virginia Institute for Psychiatric and Behavioural Genetics
M J Wright (Author) - QIMR Berghofer Medical Research Institute
G B Hall (Author) - McMaster University, Canada
G M MacQueen (Author) - University of Calgary, Canada
E M Frey (Author) - University of Regensburg, Germany
A Carballedo (Author) - University of Dublin, Ireland
L S van Velzen (Author) - VU University Medical Centre, Netherlands
M J van Tol (Author) - University of Groningen, Netherlands
N J van der Wee (Author) - Leiden University, Netherlands
I M Veer (Author) - University of Groningen, Germany
H Walter (Author) - University of Groningen, Germany
K Schnell (Author) - University Hospital Heidelberg, Germany
E Schramm (Author) - University Medical Center Freiburg, Germany
C Normann (Author) - University Medical Center Freiburg, Germany
D Schoepf (Author) - University of Bonn, Germany
C Konrad (Author) - Philipps-University Marburg, Germany
B Zurowski (Author) - University of Lübeck, Germany
T Nickson (Author) - University of Edinburgh, United Kingdom
M Papmeyer (Author) - University of Edinburgh, United Kingdom
A M McIntosh (Author) - University of Edinburgh, United Kingdom
H C Whalley (Author) - University of Edinburgh, United Kingdom
J E Sussmann (Author) - University of Edinburgh, United Kingdom
B R Godlewska (Author) - Warneford Hospital
P J Cowen (Author) - Warneford Hospital
F H Fischer (Author) - Charité Universitätsmedizin, Germany
P M Thompson (Author) - University of Southern California, United States
M Rose (Author) - Charité Universitätsmedizin, Germany
D P Hibar (Author) - University of Southern California, United States
B W J H Penninx (Author) - VU University Medical Centre, Netherlands
Publication details: Molecular Psychiatry, Vol.21, pp.806-812
Publisher: Nature Publishing Group
Date published: 2016
DOI: 10.1038/mp.2015.69
ISSN: 1359-4184; 1359-4184
Copyright note: Copyright © 2015 The Author. This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/ by/4.0/
Organisation Unit: University of the Sunshine Coast, Queensland; Thompson Institute
Language: English
Record Identifier: 99450194102621
Output Type: Journal article
Research Statement: false

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Web Of Science research areas: Biochemistry & Molecular Biology; Neurosciences; Psychiatry

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