Abstract

A key objective in the field of translational psychiatry over the past few decades has been to identify the brain correlates of major depressive disorder (MDD). Identifying measurable indicators of brain processes associated with MDD could facilitate the detection of individuals at risk, and the development of novel treatments, the monitoring of treatment effects, and predicting who might benefit most from treatments that target specific brain mechanisms. However, despite intensive neuroimaging research towards this effort, underpowered studies and a lack of reproducible findings have hindered progress. Here, we discuss the work of the ENIGMA Major Depressive Disorder (MDD) Consortium, which was established to address issues of poor replication, unreliable results, and overestimation of effect sizes in previous studies. The ENIGMA MDD Consortium currently includes data from 45 MDD study cohorts from 14 countries across six continents. The primary aim of ENIGMA MDD is to identify structural and functional brain alterations associated with MDD that can be reliably detected and replicated across cohorts worldwide. A secondary goal is to investigate how demographic, genetic, clinical, psychological, and environmental factors affect these associations. In this review, we summarize findings of the ENIGMA MDD disease working group to date and discuss future directions. We also highlight the challenges and benefits of large-scale data sharing for mental health research.

Details

Title
ENIGMA MDD: seven years of global neuroimaging studies of major depression through worldwide data sharing
Author
Schmaal Lianne 1   VIAFID ORCID Logo  ; Pozzi, Elena 1 ; C Ho Tiffany 2 ; van Velzen Laura S 1 ; Veer, Ilya M 3 ; Opel Nils 4 ; Van Someren Eus J W 5 ; Han Laura K M 6   VIAFID ORCID Logo  ; Aftanas Lybomir 7 ; Aleman André 8 ; Baune, Bernhard T 9 ; Berger, Klaus 10 ; Blanken, Tessa F 11 ; Capitão Liliana 12   VIAFID ORCID Logo  ; Couvy-Duchesne Baptiste 13 ; R Cullen Kathryn 14 ; Dannlowski Udo 4 ; Davey, Christopher 15   VIAFID ORCID Logo  ; Erwin-Grabner, Tracy 16 ; Evans, Jennifer 17 ; Frodl, Thomas 18 ; Fu Cynthia H Y 19 ; Godlewska Beata 20 ; Gotlib, Ian H 21 ; Goya-Maldonado, Roberto 16 ; Grabe, Hans J 22   VIAFID ORCID Logo  ; Groenewold, Nynke A 23 ; Grotegerd Dominik 4 ; Gruber, Oliver 24 ; Gutman, Boris A 25 ; Hall, Geoffrey B 26 ; Harrison, Ben J 27 ; Hatton, Sean N 28   VIAFID ORCID Logo  ; Hermesdorf, Marco 10 ; Hickie, Ian B 28 ; Hilland Eva 29 ; Benson, Irungu 30 ; Jonassen Rune 31 ; Kelly, Sinead 32 ; Kircher Tilo 33 ; Klimes-Dougan Bonnie 14 ; Krug Axel 33   VIAFID ORCID Logo  ; Landrø, Nils Inge 34 ; Lagopoulos, Jim 35 ; Leerssen Jeanne 11 ; Li, Meng 18 ; Linden David E J 36   VIAFID ORCID Logo  ; MacMaster, Frank P 37 ; M McIntosh Andrew 38   VIAFID ORCID Logo  ; Mehler David M A 39 ; Nenadić Igor 40 ; Penninx Brenda W J H 6 ; Portella, Maria J 41 ; Reneman Liesbeth 42 ; Rentería, Miguel E 43   VIAFID ORCID Logo  ; Sacchet, Matthew D 44 ; G Sämann Philipp 45 ; Schrantee Anouk 42 ; Sim, Kang 46   VIAFID ORCID Logo  ; Soares, Jair C 30 ; Stein, Dan J 47   VIAFID ORCID Logo  ; Tozzi Leonardo 48   VIAFID ORCID Logo  ; van Der Wee Nic J A 49 ; van, Tol Marie-José 50   VIAFID ORCID Logo  ; Vermeiren, Robert 51 ; Vives-Gilabert, Yolanda 52 ; Walter, Henrik 53   VIAFID ORCID Logo  ; Martin, Walter 54 ; Whalley, Heather C 38   VIAFID ORCID Logo  ; Wittfeld Katharina 22   VIAFID ORCID Logo  ; Whittle, Sarah 27 ; Wright, Margaret J 55   VIAFID ORCID Logo  ; Yang, Tony T 56 ; Carlos, Zarate, Jr 57 ; Thomopoulos, Sophia I 58 ; Jahanshad Neda 58   VIAFID ORCID Logo  ; Thompson, Paul M 58 ; Veltman, Dick J 6 

1  Orygen, The National Centre of Excellence in Youth Mental Health, Parkville, Australia (GRID:grid.488501.0); The University of Melbourne, Centre for Youth Mental Health, Parkville, Australia (GRID:grid.1008.9) (ISNI:0000 0001 2179 088X) 
2  Stanford University, Department of Psychology, Stanford, USA (GRID:grid.168010.e) (ISNI:0000000419368956); Stanford University, Department of Psychiatry & Behavioral Sciences, Stanford, USA (GRID:grid.168010.e) (ISNI:0000000419368956); University of California, Department of Psychiatry & Weill Institute for Neurosciences, San Francisco, USA (GRID:grid.266102.1) (ISNI:0000 0001 2297 6811) 
3  Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Division of Mind and Brain Research, Department of Psychiatry and Psychotherapy CCM, Berlin, Germany (GRID:grid.1008.9) 
4  University of Münster, Department of Psychiatry, Münster, Germany (GRID:grid.5949.1) (ISNI:0000 0001 2172 9288) 
5  Netherlands Institute for Neuroscience (NIN), an institute of the Royal Netherlands Academy of Arts and Sciences, Department of Sleep and Cognition, Amsterdam, Netherlands (GRID:grid.419918.c) (ISNI:0000 0001 2171 8263); VU University Amsterdam, Department of Integrative Neurophysiology, Center for Neurogenomics and Cognitive Research (CNCR), Amsterdam Neuroscience, Amsterdam, The Netherlands (GRID:grid.12380.38) (ISNI:0000 0004 1754 9227); Vrije Universiteit Amsterdam, Amsterdam Neuroscience, Amsterdam Public Health Research Institute, Department of Psychiatry, Amsterdam UMC, Amsterdam, The Netherlands (GRID:grid.484519.5) 
6  Vrije Universiteit Amsterdam, Amsterdam Neuroscience, Amsterdam Public Health Research Institute, Department of Psychiatry, Amsterdam UMC, Amsterdam, The Netherlands (GRID:grid.484519.5) 
7  FSSBI Scientific Research Institute of Physiology & Basic Medicine, Laboratory of Affective, Cognitive & Translational Neuroscience, Novosibirsk, Russia (GRID:grid.484519.5); Novosibirsk State University, Department of Neuroscience, Novosibirsk, Russia (GRID:grid.4605.7) (ISNI:0000000121896553) 
8  University Medical Center Groningen, University of Groningen, Department of Biomedical Sciences of Cells and Systems, Groningen, The Netherlands (GRID:grid.4605.7) 
9  University of Münster, Department of Psychiatry, Münster, Germany (GRID:grid.5949.1) (ISNI:0000 0001 2172 9288); University of Melbourne, Department of Psychiatry, Melbourne, Australia (GRID:grid.1008.9) (ISNI:0000 0001 2179 088X); University of Melbourne, The Florey Institute of Neuroscience and Mental Health, Melbourne, Australia (GRID:grid.1008.9) (ISNI:0000 0001 2179 088X) 
10  University of Münster, Institute of Epidemiology and Social Medicine, Münster, Germany (GRID:grid.5949.1) (ISNI:0000 0001 2172 9288) 
11  Netherlands Institute for Neuroscience (NIN), an institute of the Royal Netherlands Academy of Arts and Sciences, Department of Sleep and Cognition, Amsterdam, Netherlands (GRID:grid.419918.c) (ISNI:0000 0001 2171 8263); VU University Amsterdam, Department of Integrative Neurophysiology, Center for Neurogenomics and Cognitive Research (CNCR), Amsterdam Neuroscience, Amsterdam, The Netherlands (GRID:grid.12380.38) (ISNI:0000 0004 1754 9227) 
12  Oxford University, Department of Psychiatry, Oxford, UK (GRID:grid.4991.5) (ISNI:0000 0004 1936 8948); Oxford Health NHS Foundation Trust, Oxford, UK (GRID:grid.451190.8) (ISNI:0000 0004 0573 576X) 
13  the University of Queensland, Institute for Molecular Bioscience, Brisbane, Australia (GRID:grid.1003.2) (ISNI:0000 0000 9320 7537) 
14  University of Minnesota, Department of Psychology, Minneapolis, USA (GRID:grid.17635.36) (ISNI:0000000419368657) 
15  University of Melbourne, Department of Psychiatry, Melbourne, Australia (GRID:grid.1008.9) (ISNI:0000 0001 2179 088X) 
16  University Medical Center Göttingen, Laboratory of Systems Neuroscience and Imaging in Psychiatry (SNIP-Lab), Göttingen, Germany (GRID:grid.411984.1) (ISNI:0000 0001 0482 5331) 
17  Experimental Therapeutics Branch, NIMH, NIH, Bethesda, USA (GRID:grid.411984.1) 
18  Jena University Hospital, Department of Psychiatry and Psychotherapy, Jena, Germany (GRID:grid.275559.9) (ISNI:0000 0000 8517 6224) 
19  University of East London, School of Psychology, London, UK (GRID:grid.60969.30) (ISNI:0000 0001 2189 1306); Centre for Affective Disorders, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, London, UK (GRID:grid.13097.3c) (ISNI:0000 0001 2322 6764) 
20  Oxford University, Department of Psychiatry, Oxford, UK (GRID:grid.4991.5) (ISNI:0000 0004 1936 8948) 
21  Stanford University, Department of Psychology, Stanford, USA (GRID:grid.168010.e) (ISNI:0000000419368956) 
22  University Medicine Greifswald, Department of Psychiatry and Psychotherapy, Greifswald, Germany (GRID:grid.5603.0); German Center for Neurodegenerative Diseases (DZNE), Site Rostock/Greifswald, Germany (GRID:grid.424247.3) (ISNI:0000 0004 0438 0426) 
23  University of Cape Town, Department of Psychiatry & Mental Health, Cape Town, South Africa (GRID:grid.7836.a) (ISNI:0000 0004 1937 1151) 
24  Heidelberg University Hospital, Section for Experimental Psychopathology and Neuroimaging, Department of General Psychiatry, Heidelberg, Germany (GRID:grid.5253.1) (ISNI:0000 0001 0328 4908) 
25  Illinois Institute of Technology, Chicago, USA (GRID:grid.62813.3e) (ISNI:0000 0004 1936 7806) 
26  McMaster University, Department of Psychology, Neuroscience & Behaviour, Hamilton, Canada (GRID:grid.25073.33) (ISNI:0000 0004 1936 8227) 
27  The University of Melbourne & Melbourne Health, Melbourne Neuropsychiatry Centre, Department of Psychiatry, Melbourne, Australia (GRID:grid.1008.9) (ISNI:0000 0001 2179 088X) 
28  University of Sydney, Brain and Mind Centre, Camperdown, Australia (GRID:grid.1013.3) (ISNI:0000 0004 1936 834X) 
29  University of Oslo, Clinical Neuroscience Research Group, Department of Psychology, Oslo, Norway (GRID:grid.5510.1) (ISNI:0000 0004 1936 8921); Diakonhjemmet Hospital, Department of Psychiatry, Oslo, Norway (GRID:grid.413684.c) (ISNI:0000 0004 0512 8628); Institute of Clinical Medicine, University of Oslo, Norwegian Centre for Mental Disorders Research (NORMENT), Oslo, Norway (GRID:grid.5510.1) (ISNI:0000 0004 1936 8921) 
30  The University of Texas Health Science Center at Houston, Department of Psychiatry & Behavioral Sciences, Houston, USA (GRID:grid.267308.8) (ISNI:0000 0000 9206 2401) 
31  Oslo Metropolitan University, Faculty of Health Sciences, Oslo, Norway (GRID:grid.267308.8) 
32  Beth Israel Deaconess Medical Centre, Harvard Medical School, Boston, USA (GRID:grid.267308.8) 
33  University of Marburg, Department of Psychiatry and Psychotherapy, Marburg, Germany (GRID:grid.10253.35) (ISNI:0000 0004 1936 9756) 
34  University of Oslo, Clinical Neuroscience Research Group, Department of Psychology, Oslo, Norway (GRID:grid.5510.1) (ISNI:0000 0004 1936 8921); Diakonhjemmet Hospital, Department of Psychiatry, Oslo, Norway (GRID:grid.413684.c) (ISNI:0000 0004 0512 8628) 
35  University of the Sunshine Coast, Sunshine Coast Mind and Neuroscience Thompson Institute, Birtinya, Australia (GRID:grid.1034.6) (ISNI:0000 0001 1555 3415) 
36  Cardiff University, Division of Psychological Medicine and Clinical Neurosciences, Cardiff, UK (GRID:grid.5600.3) (ISNI:0000 0001 0807 5670); Cardiff University, MRC Center for Neuropsychiatric Genetics and Genomics, Cardiff, UK (GRID:grid.5600.3) (ISNI:0000 0001 0807 5670); Cardiff University Brain Research Imaging Center, Cardiff University, Cardiff, UK (GRID:grid.5600.3) (ISNI:0000 0001 0807 5670) 
37  University of Calgary, Addictions and Mental Health Strategic Clinical Network, Psychiatry and Pediatrics, Calgary, Canada (GRID:grid.22072.35) (ISNI:0000 0004 1936 7697) 
38  University of Edinburgh, Centre for Clinical Brain Science, Edinburgh, UK (GRID:grid.4305.2) (ISNI:0000 0004 1936 7988) 
39  University of Münster, Department of Psychiatry, Münster, Germany (GRID:grid.5949.1) (ISNI:0000 0001 2172 9288); Cardiff University, MRC Center for Neuropsychiatric Genetics and Genomics, Cardiff, UK (GRID:grid.5600.3) (ISNI:0000 0001 0807 5670); Cardiff University Brain Research Imaging Center, Cardiff University, Cardiff, UK (GRID:grid.5600.3) (ISNI:0000 0001 0807 5670) 
40  University of Marburg, Department of Psychiatry and Psychotherapy, Marburg, Germany (GRID:grid.10253.35) (ISNI:0000 0004 1936 9756); Marburg University Hospital UKGM, Marburg, Germany (GRID:grid.10253.35) 
41  Institut d’Investigació Biomèdica-Sant Pau, Barcelona, Spain (GRID:grid.484519.5); CIBERSAM, Madrid, Spain (GRID:grid.418264.d) (ISNI:0000 0004 1762 4012); Universitat Autònoma de Barcelona, Barcelona, Spain (GRID:grid.7080.f) 
42  location AMC, Amsterdam UMC, Department of Radiology and Nuclear Medicine, Amsterdam, The Netherlands (GRID:grid.5650.6) (ISNI:0000000404654431) 
43  QIMR Berghofer Medical Research Institute, Department of Genetics & Computational Biology, Brisbane, Australia (GRID:grid.1049.c) (ISNI:0000 0001 2294 1395) 
44  Center for Depression, Anxiety, and Stress Research, McLean Hospital, Harvard Medical School, Belmont, USA (GRID:grid.240206.2) (ISNI:0000 0000 8795 072X) 
45  Max Planck Institute of Psychiatry, Munich, Germany (GRID:grid.419548.5) (ISNI:0000 0000 9497 5095) 
46  West Region/Institute of Mental Health, Singapore, Singapore (GRID:grid.5650.6); Yong Loo Lin School of Medicine/National University of Singapore, Singapore, Singapore (GRID:grid.4280.e) (ISNI:0000 0001 2180 6431) 
47  University of Cape Town, SA MRC Research Unit on Risk & Resilience in Mental Disorders, Department of Psychiatry & Neuroscience Institute, Cape Town, South Africa (GRID:grid.7836.a) (ISNI:0000 0004 1937 1151) 
48  Stanford University, Department of Psychiatry & Behavioral Sciences, Stanford, USA (GRID:grid.168010.e) (ISNI:0000000419368956) 
49  Leiden University Medical Center, Department of Psychiatry, Leiden, The Netherlands (GRID:grid.10419.3d) (ISNI:0000000089452978); Leiden University Medical Center, Leiden Institute for Brain and Cognition, Leiden, The Netherlands (GRID:grid.10419.3d) (ISNI:0000000089452978) 
50  University Medical Center Groningen, University of Groningen, Department of Biomedical Sciences of Cells and Systems, Groningen, The Netherlands (GRID:grid.10419.3d) 
51  Leiden University Medical Center, Curium-LUMC, Leiden, The Netherlands (GRID:grid.10419.3d) (ISNI:0000000089452978) 
52  Instituto ITACA, Universitat Politècnica de València, Valencia, Spain (GRID:grid.157927.f) (ISNI:0000 0004 1770 5832) 
53  Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Division of Mind and Brain Research, Department of Psychiatry and Psychotherapy CCM, Berlin, Germany (GRID:grid.157927.f) 
54  Department of Psychiatry and Psychotherapy, Jena, Germany (GRID:grid.157927.f); Clinical Affective Neuroimaging Laboratory, Leibniz Institute for Neurobiology, Magdeburg, Germany (GRID:grid.418723.b) (ISNI:0000 0001 2109 6265) 
55  The University of Queensland, Queensland Brain Institute, Brisbane, Australia (GRID:grid.1003.2) (ISNI:0000 0000 9320 7537); The University of Queensland, Centre for Advanced Imaging, Brisbane, Australia (GRID:grid.1003.2) (ISNI:0000 0000 9320 7537) 
56  University of California, Department of Psychiatry & Weill Institute for Neurosciences, San Francisco, USA (GRID:grid.266102.1) (ISNI:0000 0001 2297 6811) 
57  Section on the Neurobiology and Treatment of Mood Disorders, National Institute of Mental Health, Bethesda, USA (GRID:grid.416868.5) (ISNI:0000 0004 0464 0574) 
58  University of Southern California, Imaging Genetics Center, Mark and Mary Stevens Neuroimaging and Informatics Institute, Keck School of Medicine, Marina del Rey, USA (GRID:grid.42505.36) (ISNI:0000 0001 2156 6853) 
Publication year
2020
Publication date
2020
Publisher
Nature Publishing Group
e-ISSN
21583188
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1038/s41398-020-0842-6
ProQuest document ID
2407754162
Copyright
© The Author(s) 2020. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.