Review

. 2020 May 29;10(1):172.

doi: 10.1038/s41398-020-0842-6.

ENIGMA MDD: seven years of global neuroimaging studies of major depression through worldwide data sharing

Lianne Schmaal^{1

2}, Elena Pozzi^{3

4}, Tiffany C Ho^{5

6

7}, Laura S van Velzen^{3

4}, Ilya M Veer⁸, Nils Opel⁹, Eus J W Van Someren^{10

11

12}, Laura K M Han¹², Lybomir Aftanas^{13

14}, André Aleman¹⁵, Bernhard T Baune^{9

16

17}, Klaus Berger¹⁸, Tessa F Blanken^{10

11}, Liliana Capitão^{19

20}, Baptiste Couvy-Duchesne²¹, Kathryn R Cullen²², Udo Dannlowski⁹, Christopher Davey¹⁶, Tracy Erwin-Grabner²³, Jennifer Evans²⁴, Thomas Frodl²⁵, Cynthia H Y Fu^{26

27}, Beata Godlewska¹⁹, Ian H Gotlib⁵, Roberto Goya-Maldonado²³, Hans J Grabe^{28

29}, Nynke A Groenewold³⁰, Dominik Grotegerd⁹, Oliver Gruber³¹, Boris A Gutman³², Geoffrey B Hall³³, Ben J Harrison³⁴, Sean N Hatton³⁵, Marco Hermesdorf¹⁸, Ian B Hickie³⁵, Eva Hilland^{36

37

38}, Benson Irungu³⁹, Rune Jonassen⁴⁰, Sinead Kelly⁴¹, Tilo Kircher⁴², Bonnie Klimes-Dougan²², Axel Krug⁴², Nils Inge Landrø^{36

37}, Jim Lagopoulos⁴³, Jeanne Leerssen^{10

11}, Meng Li²⁵, David E J Linden^{44

45

46}, Frank P MacMaster⁴⁷, Andrew M McIntosh⁴⁸, David M A Mehler^{9

45

46}, Igor Nenadić^{42

49}, Brenda W J H Penninx¹², Maria J Portella^{50

51

52}, Liesbeth Reneman⁵³, Miguel E Rentería⁵⁴, Matthew D Sacchet⁵⁵, Philipp G Sämann⁵⁶, Anouk Schrantee⁵³, Kang Sim^{57

58}, Jair C Soares³⁹, Dan J Stein⁵⁹, Leonardo Tozzi⁶, Nic J A van Der Wee^{60

61}, Marie-José van Tol¹⁵, Robert Vermeiren⁶², Yolanda Vives-Gilabert⁶³, Henrik Walter⁸, Martin Walter^{64

65}, Heather C Whalley⁴⁸, Katharina Wittfeld^{28

29}, Sarah Whittle³⁴, Margaret J Wright^{66

67}, Tony T Yang⁷, Carlos Zarate Jr⁶⁸, Sophia I Thomopoulos⁶⁹, Neda Jahanshad⁶⁹, Paul M Thompson⁶⁹, Dick J Veltman¹²

Affiliations

¹ Orygen, The National Centre of Excellence in Youth Mental Health, Parkville, VIC, Australia. lianne.schmaal@unimelb.edu.au.
² Centre for Youth Mental Health, The University of Melbourne, Parkville, VIC, Australia. lianne.schmaal@unimelb.edu.au.
³ Orygen, The National Centre of Excellence in Youth Mental Health, Parkville, VIC, Australia.
⁴ Centre for Youth Mental Health, The University of Melbourne, Parkville, VIC, Australia.
⁵ Department of Psychology, Stanford University, Stanford, CA, USA.
⁶ Department of Psychiatry & Behavioral Sciences, Stanford University, Stanford, CA, USA.
⁷ Department of Psychiatry & Weill Institute for Neurosciences, University of California, San Francisco, CA, USA.
⁸ Division of Mind and Brain Research, Department of Psychiatry and Psychotherapy CCM, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany.
⁹ Department of Psychiatry, University of Münster, Münster, Germany.
¹⁰ Department of Sleep and Cognition, Netherlands Institute for Neuroscience (NIN), an institute of the Royal Netherlands Academy of Arts and Sciences, Amsterdam, Netherlands.
¹¹ Department of Integrative Neurophysiology, Center for Neurogenomics and Cognitive Research (CNCR), Amsterdam Neuroscience, VU University Amsterdam, Amsterdam, The Netherlands.
¹² Department of Psychiatry, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam Neuroscience, Amsterdam Public Health Research Institute, Amsterdam, The Netherlands.
¹³ FSSBI Scientific Research Institute of Physiology & Basic Medicine, Laboratory of Affective, Cognitive & Translational Neuroscience, Novosibirsk, Russia.
¹⁴ Department of Neuroscience, Novosibirsk State University, Novosibirsk, Russia.
¹⁵ Department of Biomedical Sciences of Cells and Systems, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
¹⁶ Department of Psychiatry, University of Melbourne, Melbourne, VIC, Australia.
¹⁷ The Florey Institute of Neuroscience and Mental Health, University of Melbourne, Melbourne, VIC, Australia.
¹⁸ Institute of Epidemiology and Social Medicine, University of Münster, Münster, Germany.
¹⁹ Department of Psychiatry, Oxford University, Oxford, UK.
²⁰ Oxford Health NHS Foundation Trust, Oxford, UK.
²¹ Institute for Molecular Bioscience, the University of Queensland, Brisbane, QLD, Australia.
²² Department of Psychology, University of Minnesota, Minneapolis, MN, USA.
²³ Laboratory of Systems Neuroscience and Imaging in Psychiatry (SNIP-Lab), University Medical Center Göttingen, Göttingen, Germany.
²⁴ Experimental Therapeutics Branch, NIMH, NIH, Bethesda, MD, USA.
²⁵ Department of Psychiatry and Psychotherapy, Jena University Hospital, Jena, Germany.
²⁶ School of Psychology, University of East London, London, UK.
²⁷ Centre for Affective Disorders, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
²⁸ Department of Psychiatry and Psychotherapy, University Medicine Greifswald, Greifswald, Germany.
²⁹ German Center for Neurodegenerative Diseases (DZNE), Site Rostock/Greifswald, Germany.
³⁰ Department of Psychiatry & Mental Health, University of Cape Town, Cape Town, South Africa.
³¹ Section for Experimental Psychopathology and Neuroimaging, Department of General Psychiatry, Heidelberg University Hospital, Heidelberg, Germany.
³² Illinois Institute of Technology, Chicago, IL, USA.
³³ Department of Psychology, Neuroscience & Behaviour, McMaster University, Hamilton, ON, Canada.
³⁴ Melbourne Neuropsychiatry Centre, Department of Psychiatry, The University of Melbourne & Melbourne Health, Melbourne, VIC, Australia.
³⁵ Brain and Mind Centre, University of Sydney, Camperdown, NSW, Australia.
³⁶ Clinical Neuroscience Research Group, Department of Psychology, University of Oslo, Oslo, Norway.
³⁷ Department of Psychiatry, Diakonhjemmet Hospital, Oslo, Norway.
³⁸ Norwegian Centre for Mental Disorders Research (NORMENT), Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
³⁹ Department of Psychiatry & Behavioral Sciences, The University of Texas Health Science Center at Houston, Houston, TX, USA.
⁴⁰ Faculty of Health Sciences, Oslo Metropolitan University, Oslo, Norway.
⁴¹ Beth Israel Deaconess Medical Centre, Harvard Medical School, Boston, MA, USA.
⁴² Department of Psychiatry and Psychotherapy, University of Marburg, Marburg, Germany.
⁴³ Sunshine Coast Mind and Neuroscience Thompson Institute, University of the Sunshine Coast, Birtinya, QLD, Australia.
⁴⁴ Division of Psychological Medicine and Clinical Neurosciences, Cardiff University, Cardiff, UK.
⁴⁵ MRC Center for Neuropsychiatric Genetics and Genomics, Cardiff University, Cardiff, UK.
⁴⁶ Cardiff University Brain Research Imaging Center, Cardiff University, Cardiff, UK.
⁴⁷ Psychiatry and Pediatrics, University of Calgary, Addictions and Mental Health Strategic Clinical Network, Calgary, AB, Canada.
⁴⁸ Centre for Clinical Brain Science, University of Edinburgh, Edinburgh, UK.
⁴⁹ Marburg University Hospital UKGM, Marburg, Germany.
⁵⁰ Institut d'Investigació Biomèdica-Sant Pau, Barcelona, Spain.
⁵¹ CIBERSAM, Madrid, Spain.
⁵² Universitat Autònoma de Barcelona, Barcelona, Spain.
⁵³ Department of Radiology and Nuclear Medicine, location AMC, Amsterdam UMC, Amsterdam, The Netherlands.
⁵⁴ Department of Genetics & Computational Biology, QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia.
⁵⁵ Center for Depression, Anxiety, and Stress Research, McLean Hospital, Harvard Medical School, Belmont, MA, USA.
⁵⁶ Max Planck Institute of Psychiatry, Munich, Germany.
⁵⁷ West Region/Institute of Mental Health, Singapore, Singapore.
⁵⁸ Yong Loo Lin School of Medicine/National University of Singapore, Singapore, Singapore.
⁵⁹ SA MRC Research Unit on Risk & Resilience in Mental Disorders, Department of Psychiatry & Neuroscience Institute, University of Cape Town, Cape Town, South Africa.
⁶⁰ Department of Psychiatry, Leiden University Medical Center, Leiden, The Netherlands.
⁶¹ Leiden Institute for Brain and Cognition, Leiden University Medical Center, Leiden, The Netherlands.
⁶² Curium-LUMC, Leiden University Medical Center, Leiden, The Netherlands.
⁶³ Instituto ITACA, Universitat Politècnica de València, Valencia, Spain.
⁶⁴ Department of Psychiatry and Psychotherapy, Jena, Germany.
⁶⁵ Clinical Affective Neuroimaging Laboratory, Leibniz Institute for Neurobiology, Magdeburg, Germany.
⁶⁶ Queensland Brain Institute, The University of Queensland, Brisbane, QLD, Australia.
⁶⁷ Centre for Advanced Imaging, The University of Queensland, Brisbane, QLD, Australia.
⁶⁸ Section on the Neurobiology and Treatment of Mood Disorders, National Institute of Mental Health, Bethesda, MD, USA.
⁶⁹ Imaging Genetics Center, Mark and Mary Stevens Neuroimaging and Informatics Institute, Keck School of Medicine, University of Southern California, Marina del Rey, CA, USA.

PMID: 32472038
PMCID: PMC7260219
DOI: 10.1038/s41398-020-0842-6

Review

ENIGMA MDD: seven years of global neuroimaging studies of major depression through worldwide data sharing

Lianne Schmaal et al. Transl Psychiatry. 2020.

. 2020 May 29;10(1):172.

doi: 10.1038/s41398-020-0842-6.

Authors

Affiliations

¹ Orygen, The National Centre of Excellence in Youth Mental Health, Parkville, VIC, Australia. lianne.schmaal@unimelb.edu.au.
² Centre for Youth Mental Health, The University of Melbourne, Parkville, VIC, Australia. lianne.schmaal@unimelb.edu.au.
³ Orygen, The National Centre of Excellence in Youth Mental Health, Parkville, VIC, Australia.
⁴ Centre for Youth Mental Health, The University of Melbourne, Parkville, VIC, Australia.
⁵ Department of Psychology, Stanford University, Stanford, CA, USA.
⁶ Department of Psychiatry & Behavioral Sciences, Stanford University, Stanford, CA, USA.
⁷ Department of Psychiatry & Weill Institute for Neurosciences, University of California, San Francisco, CA, USA.
⁸ Division of Mind and Brain Research, Department of Psychiatry and Psychotherapy CCM, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany.
⁹ Department of Psychiatry, University of Münster, Münster, Germany.
¹⁰ Department of Sleep and Cognition, Netherlands Institute for Neuroscience (NIN), an institute of the Royal Netherlands Academy of Arts and Sciences, Amsterdam, Netherlands.
¹¹ Department of Integrative Neurophysiology, Center for Neurogenomics and Cognitive Research (CNCR), Amsterdam Neuroscience, VU University Amsterdam, Amsterdam, The Netherlands.
¹² Department of Psychiatry, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam Neuroscience, Amsterdam Public Health Research Institute, Amsterdam, The Netherlands.
¹³ FSSBI Scientific Research Institute of Physiology & Basic Medicine, Laboratory of Affective, Cognitive & Translational Neuroscience, Novosibirsk, Russia.
¹⁴ Department of Neuroscience, Novosibirsk State University, Novosibirsk, Russia.
¹⁵ Department of Biomedical Sciences of Cells and Systems, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
¹⁶ Department of Psychiatry, University of Melbourne, Melbourne, VIC, Australia.
¹⁷ The Florey Institute of Neuroscience and Mental Health, University of Melbourne, Melbourne, VIC, Australia.
¹⁸ Institute of Epidemiology and Social Medicine, University of Münster, Münster, Germany.
¹⁹ Department of Psychiatry, Oxford University, Oxford, UK.
²⁰ Oxford Health NHS Foundation Trust, Oxford, UK.
²¹ Institute for Molecular Bioscience, the University of Queensland, Brisbane, QLD, Australia.
²² Department of Psychology, University of Minnesota, Minneapolis, MN, USA.
²³ Laboratory of Systems Neuroscience and Imaging in Psychiatry (SNIP-Lab), University Medical Center Göttingen, Göttingen, Germany.
²⁴ Experimental Therapeutics Branch, NIMH, NIH, Bethesda, MD, USA.
²⁵ Department of Psychiatry and Psychotherapy, Jena University Hospital, Jena, Germany.
²⁶ School of Psychology, University of East London, London, UK.
²⁷ Centre for Affective Disorders, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
²⁸ Department of Psychiatry and Psychotherapy, University Medicine Greifswald, Greifswald, Germany.
²⁹ German Center for Neurodegenerative Diseases (DZNE), Site Rostock/Greifswald, Germany.
³⁰ Department of Psychiatry & Mental Health, University of Cape Town, Cape Town, South Africa.
³¹ Section for Experimental Psychopathology and Neuroimaging, Department of General Psychiatry, Heidelberg University Hospital, Heidelberg, Germany.
³² Illinois Institute of Technology, Chicago, IL, USA.
³³ Department of Psychology, Neuroscience & Behaviour, McMaster University, Hamilton, ON, Canada.
³⁴ Melbourne Neuropsychiatry Centre, Department of Psychiatry, The University of Melbourne & Melbourne Health, Melbourne, VIC, Australia.
³⁵ Brain and Mind Centre, University of Sydney, Camperdown, NSW, Australia.
³⁶ Clinical Neuroscience Research Group, Department of Psychology, University of Oslo, Oslo, Norway.
³⁷ Department of Psychiatry, Diakonhjemmet Hospital, Oslo, Norway.
³⁸ Norwegian Centre for Mental Disorders Research (NORMENT), Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
³⁹ Department of Psychiatry & Behavioral Sciences, The University of Texas Health Science Center at Houston, Houston, TX, USA.
⁴⁰ Faculty of Health Sciences, Oslo Metropolitan University, Oslo, Norway.
⁴¹ Beth Israel Deaconess Medical Centre, Harvard Medical School, Boston, MA, USA.
⁴² Department of Psychiatry and Psychotherapy, University of Marburg, Marburg, Germany.
⁴³ Sunshine Coast Mind and Neuroscience Thompson Institute, University of the Sunshine Coast, Birtinya, QLD, Australia.
⁴⁴ Division of Psychological Medicine and Clinical Neurosciences, Cardiff University, Cardiff, UK.
⁴⁵ MRC Center for Neuropsychiatric Genetics and Genomics, Cardiff University, Cardiff, UK.
⁴⁶ Cardiff University Brain Research Imaging Center, Cardiff University, Cardiff, UK.
⁴⁷ Psychiatry and Pediatrics, University of Calgary, Addictions and Mental Health Strategic Clinical Network, Calgary, AB, Canada.
⁴⁸ Centre for Clinical Brain Science, University of Edinburgh, Edinburgh, UK.
⁴⁹ Marburg University Hospital UKGM, Marburg, Germany.
⁵⁰ Institut d'Investigació Biomèdica-Sant Pau, Barcelona, Spain.
⁵¹ CIBERSAM, Madrid, Spain.
⁵² Universitat Autònoma de Barcelona, Barcelona, Spain.
⁵³ Department of Radiology and Nuclear Medicine, location AMC, Amsterdam UMC, Amsterdam, The Netherlands.
⁵⁴ Department of Genetics & Computational Biology, QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia.
⁵⁵ Center for Depression, Anxiety, and Stress Research, McLean Hospital, Harvard Medical School, Belmont, MA, USA.
⁵⁶ Max Planck Institute of Psychiatry, Munich, Germany.
⁵⁷ West Region/Institute of Mental Health, Singapore, Singapore.
⁵⁸ Yong Loo Lin School of Medicine/National University of Singapore, Singapore, Singapore.
⁵⁹ SA MRC Research Unit on Risk & Resilience in Mental Disorders, Department of Psychiatry & Neuroscience Institute, University of Cape Town, Cape Town, South Africa.
⁶⁰ Department of Psychiatry, Leiden University Medical Center, Leiden, The Netherlands.
⁶¹ Leiden Institute for Brain and Cognition, Leiden University Medical Center, Leiden, The Netherlands.
⁶² Curium-LUMC, Leiden University Medical Center, Leiden, The Netherlands.
⁶³ Instituto ITACA, Universitat Politècnica de València, Valencia, Spain.
⁶⁴ Department of Psychiatry and Psychotherapy, Jena, Germany.
⁶⁵ Clinical Affective Neuroimaging Laboratory, Leibniz Institute for Neurobiology, Magdeburg, Germany.
⁶⁶ Queensland Brain Institute, The University of Queensland, Brisbane, QLD, Australia.
⁶⁷ Centre for Advanced Imaging, The University of Queensland, Brisbane, QLD, Australia.
⁶⁸ Section on the Neurobiology and Treatment of Mood Disorders, National Institute of Mental Health, Bethesda, MD, USA.
⁶⁹ Imaging Genetics Center, Mark and Mary Stevens Neuroimaging and Informatics Institute, Keck School of Medicine, University of Southern California, Marina del Rey, CA, USA.

PMID: 32472038
PMCID: PMC7260219
DOI: 10.1038/s41398-020-0842-6

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.

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Conflict of interest statement

HJG has received travel grants and speakers honoraria from Fresenius Medical Care, Neuraxpharm, Servier and Janssen Cilag as well as research funding from Fresenius Medical Care. DJS has received grants and/or honoraria from Lundbeck and Sun. MDS has received consulting fees from Vorso Corporation. Dr. Zarate is a full-time US government employee. He is listed as a co-inventor on a patent for the use of ketamine and its metabolites in major depression and suicidal ideation. Dr. Zarate has assigned his patent rights to the US government but will share a percentage of any royalties that may be received by the government.

Figures

**Fig. 1. World map of cohorts participating in ENIGMA MDD.**
Locations of cohorts included in the ENIGMA MDD consortium in September 2019.

**Fig. 2. Connections between ENIGMA MDD and other ENIGMA working groups.**
Note: not all ENIGMA working groups are displayed in this figure. In September 2019, ENIGMA includes 50 working groups, of which 26 working groups focus on mental and neurological disorders. dMRI diffusion magnetic resonance imaging (MRI), rsfMRI resting state functional MRI, EEG electroencephalogram, tbfMRI task-based functional MRI, MDD major depressive disorder, PTSD post-traumatic stress disorder, AD anxiety disorder.

**Fig. 3. Converging findings across ENIGMA MDD studies.**
Specific characteristics of brain structure are differentially affected by MDD (or vice versa) at different stages of life. a Alterations in hippocampal and amygdala volumes and shapes are observed in adolescent-onset MDD and lower cortical surface area in adolescents with MDD. b Cortical thickness alterations and white matter abnormalities are specifically associated with adult-onset MDD and older age in individuals with MDD and/or childhood maltreatment. *This association was independent of MDD diagnosis. MDD major depressive disorder, FA fractional anisotropy, RD radial diffusivity.

**Fig. 4. Subcortical volume and cortical thickness alterations in schizophrenia, bipolar disorder, and MDD.**
Results from the ENIGMA major depressive disorder (MDD), schizophrenia (SCZ), and bipolar disorder (BD) working groups suggest that there is considerable overlap in subcortical volume a and cortical thickness b alterations across these diagnostic groups. Most widespread effects and highest effect sizes were observed in SCZ (up to Cohen’s d 0.5), followed by BD (Cohen’s d 0.3), and with more local effects and lower effect sizes in MDD (Cohen’s d 0.15). Importantly, results displayed are based on case–control comparisons within each disorder separately and are not derived from direct comparisons between patient groups. Data were analyzed with the same harmonized methods across the disorders.

See this image and copyright information in PMC

References

1. World Health Organization. Depression and other common mental disorders: global health estimates. 1–24 (2017).
1. Rush AJ, et al. Acute and longer-term outcomes in depressed outpatients requiring one or several treatment steps: a STAR*D report. Am. J. Psychiatry. 2006;163:1905–1917. - PubMed
1. Machado M, Iskedjian M, Ruiz I, Einarson TR. Remission, dropouts, and adverse drug reaction rates in major depressive disorder: a meta-analysis of head-to-head trials. Curr. Med. Res. Opin. 2006;22:1825–1837. - PubMed
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ENIGMA MDD: seven years of global neuroimaging studies of major depression through worldwide data sharing

Affiliations

ENIGMA MDD: seven years of global neuroimaging studies of major depression through worldwide data sharing

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

References

Publication types

MeSH terms

Grants and funding

LinkOut - more resources

Full Text Sources

Miscellaneous