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Mol Psychiatry. 2016 Jun;21(6):806-12. doi: 10.1038/mp.2015.69. Epub 2015 Jun 30.

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

Author information

1
Department of Psychiatry and Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, The Netherlands.
2
Department of Psychiatry and Human Behavior, University of California, Irvine, CA, USA.
3
Max Planck Institute of Psychiatry, Munich, Germany.
4
Department of Psychiatry, University of Regensburg, Regensburg, Germany.
5
Department of Psychiatry, University of Dublin, Trinity College, Dublin, Ireland.
6
Imaging Genetics Center, Department of Neurology, Keck School of Medicine, University of Southern California, Marina del Rey, CA, USA.
7
Department of Epidemiology, Erasmus MC University Medical Center, Rotterdam, The Netherlands.
8
Department of Psychiatry, Erasmus MC University Medical Center, Rotterdam, The Netherlands.
9
Departments of Radiology and Medical Informatics, Erasmus MC University Medical Center, Rotterdam, The Netherlands.
10
Imaging Science and Technology, Faculty of Applied Sciences, Delft University of Technology, Delft, The Netherlands.
11
Department of Neurology, Erasmus MC University Medical Center, Rotterdam, The Netherlands.
12
German Center for Neurodegenerative Diseases (DZNE), Rostock/Greifswald, Germany.
13
Department of Psychiatry and Psychotherapy, University Medicine Greifswald, Greifswald, Germany.
14
Helios Hospital Stralsund, Stralsund, Germany.
15
Institute of Diagnostic Radiology and Neuroradiology, University Medicine Greifswald, Greifswald, Germany.
16
Institute for Community Medicine, University Medicine Greifswald, Greifswald, Germany.
17
Clinical Research Unit, Brain and Mind Research Institute, University of Sydney, Camperdown, Australia.
18
Center for Translational Research in Systems Neuroscience and Psychiatry, Department of Psychiatry and Psychotherapy, University Medical Center, Goettingen, Germany.
19
NeuroImaging Genetics, QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia.
20
School of Psychology, University of Queensland, Brisbane, QLD, Australia.
21
Center for Advanced Imaging, University of Queensland, Brisbane, QLD, Australia.
22
Genetic Epidemiology, QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia.
23
Queensland Brain Institute, University of Queensland, Brisbane, QLD, Australia.
24
Quantitative Genetics, QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia.
25
Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond, VA, USA.
26
Department of Psychology, Neuroscience and Behaviour, McMaster University, Hamilton, ON, Canada.
27
Department of Psychiatry, Mathison Centre for Mental Health Research and Education, Hotchkiss Brain Institute, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada.
28
Department of Psychiatry and Institute of Neuroscience, University of Dublin, Trinity College Dublin, Dublin, Ireland.
29
University of Groningen, University Medical Center Groningen, NeuroImaging Center, Groningen, The Netherlands.
30
Department of Psychiatry, Leiden University Medical Center, Leiden University, Leiden, The Netherlands.
31
Leiden Institute for Brain and Cognition, Leiden, The Netherlands.
32
Department of Psychiatry and Psychotherapy, Division of Mind and Brain Research, Charité Universitätsmedizin Berlin, Berlin, Germany.
33
Department of General Psychiatry, University Hospital Heidelberg, Heidelberg, Germany.
34
Department of Psychiatry and Psychotherapy, University Medical Center Freiburg, Freiburg im Breisgau, Germany.
35
Department of Psychiatry, University of Bonn, Bonn, Germany.
36
Department of Psychiatry and Psychotherapy, Philipps-University Marburg, Marburg, Germany.
37
Center for Integrative Psychiatry, University of Lübeck, Lübeck, Germany.
38
Division of Psychiatry, University of Edinburgh, Edinburgh, UK.
39
Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK.
40
University Department of Psychiatry, Warneford Hospital, Oxford, UK.
41
Department of Psychosomatic Medicine, Center for Internal Medicine and Dermatology, Charité Universitätsmedizin, Berlin, Germany.
42
Institute for Social Medicine, Epidemology and Health Economics, Charité Universitätsmedizin, Berlin, Germany.
43
Department of Quantitative Health Sciences, University of Massachusetts Medical School, Worcester, MA, USA.

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.

PMID:
26122586
PMCID:
PMC4879183
DOI:
10.1038/mp.2015.69
[Indexed for MEDLINE]
Free PMC Article

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