Genetic Epidemiology, Psychiatric Genetics, Asthma Genetics and Statistical Genetics Laboratories investigate the pattern of disease in families, particularly identical and non-identical twins, to assess the relative importance of genes and environment in a variety of important health problems.
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PMID
26122586
TITLE
Subcortical brain alterations in major depressive disorder: findings from the ENIGMA Major Depressive Disorder working group.
ABSTRACT
NlmCategory: UNASSIGNED
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.Molecular Psychiatry advance online publication, 30 June 2015; doi:10.1038/mp.2015.69.
DATE PUBLISHED
2015 Jun 30
HISTORY
PUBSTATUS PUBSTATUSDATE
received 2014/10/27
revised 2015/03/13
accepted 2015/04/01
entrez 2015/07/01 06:00
pubmed 2015/07/01 06:00
medline 2015/07/01 06:00
AUTHORS
NAME COLLECTIVENAME LASTNAME FORENAME INITIALS AFFILIATION AFFILIATIONINFO
Schmaal L Schmaal L L Department of Psychiatry and Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, The Netherlands.
Veltman DJ Veltman D J DJ Department of Psychiatry and Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, The Netherlands.
van Erp TG van Erp T G M TG Department of Psychiatry and Human Behavior, University of California, Irvine, CA, USA.
Sämann PG Sämann P G PG Max Planck Institute of Psychiatry, Munich, Germany.
Frodl T Frodl T T 1] Department of Psychiatry, University of Regensburg, Regensburg, Germany [2] Department of Psychiatry, University of Dublin, Trinity College, Dublin, Ireland.
Jahanshad N Jahanshad N N Imaging Genetics Center, Department of Neurology, Keck School of Medicine, University of Southern California, Marina del Rey, CA, USA.
Loehrer E Loehrer E E Department of Epidemiology, Erasmus MC University Medical Center, Rotterdam, The Netherlands.
Tiemeier H Tiemeier H H 1] Department of Epidemiology, Erasmus MC University Medical Center, Rotterdam, The Netherlands [2] Department of Psychiatry, Erasmus MC University Medical Center, Rotterdam, The Netherlands.
Hofman A Hofman A A Department of Epidemiology, Erasmus MC University Medical Center, Rotterdam, The Netherlands.
Niessen WJ Niessen W J WJ 1] Departments of Radiology and Medical Informatics, Erasmus MC University Medical Center, Rotterdam, The Netherlands [2] Imaging Science and Technology, Faculty of Applied Sciences, Delft University of Technology, Delft, The Netherlands.
Vernooij MW Vernooij M W MW 1] Department of Epidemiology, Erasmus MC University Medical Center, Rotterdam, The Netherlands [2] Departments of Radiology and Medical Informatics, Erasmus MC University Medical Center, Rotterdam, The Netherlands.
Ikram MA Ikram M A MA 1] Department of Epidemiology, Erasmus MC University Medical Center, Rotterdam, The Netherlands [2] Departments of Radiology and Medical Informatics, Erasmus MC University Medical Center, Rotterdam, The Netherlands [3] Department of Neurology, Erasmus MC University Medical Center, Rotterdam, The Netherlands.
Wittfeld K Wittfeld K K German Center for Neurodegenerative Diseases (DZNE), Rostock/Greifswald, Germany.
Grabe HJ Grabe H J HJ 1] German Center for Neurodegenerative Diseases (DZNE), Rostock/Greifswald, Germany [2] Department of Psychiatry and Psychotherapy, University Medicine Greifswald, Greifswald, Germany [3] Helios Hospital Stralsund, Stralsund, Germany.
Block A Block A A Department of Psychiatry and Psychotherapy, University Medicine Greifswald, Greifswald, Germany.
Hegenscheid K Hegenscheid K K Institute of Diagnostic Radiology and Neuroradiology, University Medicine Greifswald, Greifswald, Germany.
Völzke H Völzke H H Institute for Community Medicine, University Medicine Greifswald, Greifswald, Germany.
Hoehn D Hoehn D D Max Planck Institute of Psychiatry, Munich, Germany.
Czisch M Czisch M M Max Planck Institute of Psychiatry, Munich, Germany.
Lagopoulos J Lagopoulos J J Clinical Research Unit, Brain and Mind Research Institute, University of Sydney, Camperdown, Australia.
Hatton SN Hatton S N SN Clinical Research Unit, Brain and Mind Research Institute, University of Sydney, Camperdown, Australia.
Hickie IB Hickie I B IB Clinical Research Unit, Brain and Mind Research Institute, University of Sydney, Camperdown, Australia.
Goya-Maldonado R Goya-Maldonado R R Center for Translational Research in Systems Neuroscience and Psychiatry, Department of Psychiatry and Psychotherapy, University Medical Center, Goettingen, Germany.
Krämer B Krämer B B Center for Translational Research in Systems Neuroscience and Psychiatry, Department of Psychiatry and Psychotherapy, University Medical Center, Goettingen, Germany.
Gruber O Gruber O O Center for Translational Research in Systems Neuroscience and Psychiatry, Department of Psychiatry and Psychotherapy, University Medical Center, Goettingen, Germany.
Couvy-Duchesne B Couvy-Duchesne B B 1] NeuroImaging Genetics, QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia [2] School of Psychology, University of Queensland, Brisbane, QLD, Australia [3] Center for Advanced Imaging, University of Queensland, Brisbane, QLD, Australia.
Rentería ME Rentería M E ME Genetic Epidemiology, QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia.
Strike LT Strike L T LT 1] NeuroImaging Genetics, QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia [2] School of Psychology, University of Queensland, Brisbane, QLD, Australia [3] Center for Advanced Imaging, University of Queensland, Brisbane, QLD, Australia.
Mills NT Mills N T NT 1] Genetic Epidemiology, QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia [2] Queensland Brain Institute, University of Queensland, Brisbane, QLD, Australia.
de Zubicaray GI de Zubicaray G I GI School of Psychology, University of Queensland, Brisbane, QLD, Australia.
McMahon KL McMahon K L KL Center for Advanced Imaging, University of Queensland, Brisbane, QLD, Australia.
Medland SE Medland S E SE Quantitative Genetics, QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia.
Martin NG Martin N G NG Genetic Epidemiology, QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia.
Gillespie NA Gillespie N A NA Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond, VA, USA.
Wright MJ Wright M J MJ NeuroImaging Genetics, QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia.
Hall GB Hall G B GB Department of Psychology, Neuroscience and Behaviour, McMaster University, Hamilton, ON, Canada.
MacQueen GM MacQueen G M GM Department of Psychiatry, Mathison Centre for Mental Health Research and Education, Hotchkiss Brain Institute, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada.
Frey EM Frey E M EM Department of Psychiatry, University of Regensburg, Regensburg, Germany.
Carballedo A Carballedo A A Department of Psychiatry and Institute of Neuroscience, University of Dublin, Trinity College Dublin, Dublin, Ireland.
van Velzen LS van Velzen L S LS Department of Psychiatry and Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, The Netherlands.
van Tol MJ van Tol M J MJ University of Groningen, University Medical Center Groningen, NeuroImaging Center, Groningen, The Netherlands.
van der Wee NJ van der Wee N J NJ 1] Department of Psychiatry, Leiden University Medical Center, Leiden University, Leiden, The Netherlands [2] Leiden Institute for Brain and Cognition, Leiden, The Netherlands.
Veer IM Veer I M IM Department of Psychiatry and Psychotherapy, Division of Mind and Brain Research, Charité Universitätsmedizin Berlin, Berlin, Germany.
Walter H Walter H H Department of Psychiatry and Psychotherapy, Division of Mind and Brain Research, Charité Universitätsmedizin Berlin, Berlin, Germany.
Schnell K Schnell K K Department of General Psychiatry, University Hospital Heidelberg, Heidelberg, Germany.
Schramm E Schramm E E Department of Psychiatry and Psychotherapy, University Medical Center Freiburg, Freiburg im Breisgau, Germany.
Normann C Normann C C Department of Psychiatry and Psychotherapy, University Medical Center Freiburg, Freiburg im Breisgau, Germany.
Schoepf D Schoepf D D Department of Psychiatry, University of Bonn, Bonn, Germany.
Konrad C Konrad C C Department of Psychiatry and Psychotherapy, Philipps-University Marburg, Marburg, Germany.
Zurowski B Zurowski B B Center for Integrative Psychiatry, University of Lübeck, Lübeck, Germany.
Nickson T Nickson T T Division of Psychiatry, University of Edinburgh, Edinburgh, UK.
McIntosh AM McIntosh A M AM 1] Division of Psychiatry, University of Edinburgh, Edinburgh, UK [2] Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK.
Papmeyer M Papmeyer M M Division of Psychiatry, University of Edinburgh, Edinburgh, UK.
Whalley HC Whalley H C HC Division of Psychiatry, University of Edinburgh, Edinburgh, UK.
Sussmann JE Sussmann J E JE Division of Psychiatry, University of Edinburgh, Edinburgh, UK.
Godlewska BR Godlewska B R BR University Department of Psychiatry, Warneford Hospital, Oxford, UK.
Cowen PJ Cowen P J PJ University Department of Psychiatry, Warneford Hospital, Oxford, UK.
Fischer FH Fischer F H FH 1] Department of Psychosomatic Medicine, Center for Internal Medicine and Dermatology, Charité Universitätsmedizin, Berlin, Germany [2] Institute for Social Medicine, Epidemology and Health Economics, Charité Universitätsmedizin, Berlin, Germany.
Rose M Rose M M 1] Department of Psychosomatic Medicine, Center for Internal Medicine and Dermatology, Charité Universitätsmedizin, Berlin, Germany [2] Department of Quantitative Health Sciences, University of Massachusetts Medical School, Worcester, MA, USA.
Penninx BW Penninx B W J H BW Department of Psychiatry and Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, The Netherlands.
Thompson PM Thompson P M PM Imaging Genetics Center, Department of Neurology, Keck School of Medicine, University of Southern California, Marina del Rey, CA, USA.
Hibar DP Hibar D P DP Imaging Genetics Center, Department of Neurology, Keck School of Medicine, University of Southern California, Marina del Rey, CA, USA.
INVESTIGATORS
JOURNAL
VOLUME:
ISSUE:
TITLE: Molecular psychiatry
ISOABBREVIATION: Mol. Psychiatry
YEAR: 2015
MONTH: Jun
DAY: 30
MEDLINEDATE:
SEASON:
CITEDMEDIUM: Internet
ISSN: 1476-5578
ISSNTYPE: Electronic
MEDLINE JOURNAL
MEDLINETA: Mol Psychiatry
COUNTRY: England
ISSNLINKING: 1359-4184
NLMUNIQUEID: 9607835
PUBLICATION TYPE
PUBLICATIONTYPE TEXT
JOURNAL ARTICLE
COMMENTS AND CORRECTIONS
GRANTS
GRANTID AGENCY COUNTRY
MR/K026992/1 Medical Research Council United Kingdom
P41 EB015922 NIBIB NIH HHS United States
U54 EB020406 NIBIB NIH HHS United States
104036 Wellcome Trust United Kingdom
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