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Transl Psychiatry. 2020 Mar 20;10(1):100. doi: 10.1038/s41398-020-0705-1.

ENIGMA and global neuroscience: A decade of large-scale studies of the brain in health and disease across more than 40 countries.

Thompson PM1, Jahanshad N2, Ching CRK2, Salminen LE2, Thomopoulos SI2, Bright J2, Baune BT3,4,5, Bertolín S6, Bralten J7,8, Bruin WB9, Bülow R10, Chen J11, Chye Y12, Dannlowski U3, de Kovel CGF13,14, Donohoe G15, Eyler LT16,17, Faraone SV18, Favre P19,20, Filippi CA21, Frodl T22,23,24, Garijo D25, Gil Y25,26, Grabe HJ27,28, Grasby KL29, Hajek T30,31, Han LKM32, Hatton SN33,34, Hilbert K35, Ho TC36,37, Holleran L15, Homuth G38, Hosten N10, Houenou J19,20,39, Ivanov I40, Jia T41,42,43, Kelly S44,45, Klein M7,8,46, Kwon JS47,48, Laansma MA49, Leerssen J50, Lueken U35, Nunes A30,51, Neill JO52, Opel N3, Piras F53, Piras F53, Postema MC14, Pozzi E54,55, Shatokhina N2, Soriano-Mas C6,56,57, Spalletta G53,58, Sun D59,60, Teumer A61, Tilot AK2, Tozzi L36, van der Merwe C62,63, Van Someren EJW50,64, van Wingen GA9, Völzke H61,65, Walton E66, Wang L67,68, Winkler AM21, Wittfeld K27,28, Wright MJ69,70, Yun JY71,72, Zhang G73, Zhang-James Y18,74, Adhikari BM75, Agartz I76,77,78, Aghajani M79,80, Aleman A81, Althoff RR82, Altmann A83, Andreassen OA76,84, Baron DA85, Bartnik-Olson BL86, Marie Bas-Hoogendam J87,88,89, Baskin-Sommers AR90, Bearden CE59,91, Berner LA40, Boedhoe PSW79, Brouwer RM46, Buitelaar JK92, Caeyenberghs K93, Cecil CAM94,95, Cohen RA96,97, Cole JH98,99, Conrod PJ100, De Brito SA101, de Zwarte SMC46, Dennis EL2,102,103, Desrivieres S104, Dima D105,106, Ehrlich S107, Esopenko C108, Fairchild G66, Fisher SE8,14, Fouche JP109,110, Francks C8,14, Frangou S111,112, Franke B7,8,113, Garavan HP114, Glahn DC115,116, Groenewold NA109, Gurholt TP76,84, Gutman BA117,118, Hahn T3, Harding IH119, Hernaus D120, Hibar DP121, Hillary FG122,123, Hoogman M7,8, Hulshoff Pol HE46, Jalbrzikowski M124, Karkashadze GA125, Klapwijk ET87,89, Knickmeyer RC126,127,128, Kochunov P75, Koerte IK103,129, Kong XZ14, Liew SL130,131, Lin AP132,133, Logue MW134,135,136, Luders E137,138, Macciardi F139, Mackey S114, Mayer AR140, McDonald CR33,141, McMahon AB2,142, Medland SE29, Modinos G106,143, Morey RA144,145, Mueller SC146,147, Mukherjee P148, Namazova-Baranova L125,149, Nir TM2, Olsen A150,151, Paschou P152, Pine DS153, Pizzagalli F2, Rentería ME154, Rohrer JD155, Sämann PG156, Schmaal L55,157, Schumann G43,158, Shiroishi MS2,159, Sisodiya SM160,161, Smit DJA9, Sønderby IE76,84,162, Stein DJ163, Stein JL164, Tahmasian M165, Tate DF166,167, Turner JA168, van den Heuvel OA49,79, van der Wee NJA88,89, van der Werf YD49, van Erp TGM169,170, van Haren NEM46,94, van Rooij D171, van Velzen LS55,157, Veer IM172, Veltman DJ79, Villalon-Reina JE2, Walter H172, Whelan CD173,174, Wilde EA102,175,176, Zarei M165, Zelman V177,178; ENIGMA Consortium.

Author information

1
Imaging Genetics Center, Mark and Mary Stevens Neuroimaging and Informatics Institute, Keck School of Medicine, University of Southern California, Marina del Rey, CA, USA. pthomp@usc.edu.
2
Imaging Genetics Center, Mark and Mary Stevens Neuroimaging and Informatics Institute, Keck School of Medicine, University of Southern California, Marina del Rey, CA, USA.
3
Department of Psychiatry, University of Münster, Münster, Germany.
4
Department of Psychiatry, The University of Melbourne, Melbourne, VIC, Australia.
5
The Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Melbourne, VIC, Australia.
6
Department of Psychiatry, Bellvitge University Hospital, Bellvitge Biomedical Research Institute-IDIBELL, Barcelona, Spain.
7
Department of Human Genetics, Radboud University Medical Center, Nijmegen, The Netherlands.
8
Donders Institute for Brain, Cognition and Behaviour, Radboud University, Nijmegen, The Netherlands.
9
Department of Psychiatry, Amsterdam UMC, University of Amsterdam, Amsterdam Neuroscience, Amsterdam, The Netherlands.
10
Institute for Diagnostic Radiology and Neuroradiology, University Medicine Greifswald, Greifswald, Germany.
11
Department of Computer Science and Engineering, The Ohio State University, Columbus, OH, USA.
12
Turner Institute for Brain and Mental Health, School of Psychological Sciences, Monash University, Clayton, VIC, Australia.
13
Biometris Wageningen University and Research, Wageningen, The Netherlands.
14
Language & Genetics Department, Max Planck Institute for Psycholinguistics, Nijmegen, The Netherlands.
15
The Center for Neuroimaging and Cognitive Genomics, School of Psychology, National University of Ireland, Galway, Ireland.
16
Department of Psychiatry, University of California, San Diego, La Jolla, CA, USA.
17
Desert-Pacific Mental Illness Research, Education, and Clinical Center, VA San Diego Healthcare System, San Diego, CA, USA.
18
Departments of Psychiatry and of Neuroscience and Physiology, SUNY Upstate Medical University, Syracuse, NY, USA.
19
INSERM Unit 955 Team 15 'Translational Psychiatry', Créteil, France.
20
NeuroSpin, UNIACT Lab, Psychiatry Team, CEA Saclay, Gif-Sur-Yvette, France.
21
National Institute of Mental Health, National of Health, Bethesda, MD, USA.
22
Department of Psychiatry and Psychotherapy, Otto von Guericke University Magdeburg, Magdeburg, Germany.
23
Department of Psychiatry, Trinity College Dublin, Dublin, Ireland.
24
German Center for Neurodegenerative Diseases (DZNE), Magdeburg, Germany.
25
Information Sciences Institute, University of Southern California, Marina del Rey, CA, USA.
26
Department of Computer Science, University of Southern California, Los Angeles, CA, USA.
27
Department of Psychiatry and Psychotherapy, University Medicine Greifswald, Greifswald, Germany.
28
German Center for Neurodegenerative Diseases (DZNE), Site Rostock/Greifswald, Greifswald, Germany.
29
Psychiatric Genetics, QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia.
30
Department of Psychiatry, Dalhousie University, Halifax, NS, Canada.
31
National Institute of Mental Health, Klecany, Czech Republic.
32
Department of Psychiatry, Amsterdam University Medical Centers, VU University Medical Center, GGZ inGeest, Amsterdam Neuroscience, Amsterdam, The Netherlands.
33
Center for Multimodal Imaging and Genetics, University of California, San Diego, La Jolla, CA, USA.
34
Brain and Mind Centre, University of Sydney, Sydney, Australia.
35
Department of Psychology, Humboldt-Universität zu Berlin, Berlin, Germany.
36
Department of Psychiatry & Behavioral Sciences, Stanford University, Stanford, CA, USA.
37
Department of Psychiatry & Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA, USA.
38
Interfaculty Institute for Genetics and Functional Genomics, University Medicine Greifswald, Greifswald, Germany.
39
APHP, Mondor University Hospitals, School of Medicine, DMU Impact, Psychiatry Department, Créteil, France.
40
Icahn School of Medicine at Mount Sinai, New York, NY, USA.
41
Institute of Science and Technology for Brain-Inspired Intelligence, Fudan University, Shanghai, China.
42
MOE Key Laboratory of Computational Neuroscience and Brain-Inspired Intelligence, Fudan University, Shanghai, China.
43
Centre for Population Neuroscience and Precision Medicine (PONS), MRC SGDP Centre, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK.
44
Department of Psychiatry, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
45
Department of Psychiatry, Brigham and Women's Hospital, Boston, MA, USA.
46
Department of Psychiatry, UMC Brain Center, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands.
47
Department of Psychiatry, Seoul National University College of Medicine, Seoul, Republic of Korea.
48
Department of Brain and Cognitive Sciences, Seoul National University College of Natural Sciences, Seoul, Republic of Korea.
49
Department of Anatomy & Neurosciences, Amsterdam UMC, Location VUmc, Amsterdam Neuroscience, Amsterdam, The Netherlands.
50
Department of Sleep and Cognition, Netherlands Institute for Neuroscience, Amsterdam, The Netherlands.
51
Faculty of Computer Science, Dalhousie University, Halifax, NS, Canada.
52
Child & Adolescent Psychiatry, University of California, Los Angeles, Los Angeles, CA, USA.
53
Laboratory of Neuropsychiatry, IRCCS Santa Lucia Foundation, Rome, Italy.
54
Melbourne Neuropsychiatry Centre, Department of Psychiatry, The University of Melbourne, Melbourne, VIC, Australia.
55
Orygen, The National Centre of Excellence in Youth Mental Health, Melbourne, VIC, Australia.
56
CIBERSAM-G17, Madrid, Spain.
57
Department of Psychobiology and Methodology in Health Sciences, Universitat Autònoma de Barcelona, Barcelona, Spain.
58
Department of Psychiatry and Behavioral Sciences, Baylor College of Medicine, Houston, TX, USA.
59
Department of Psychiatry and Biobehavioral Sciences, Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, Los Angeles, CA, USA.
60
Department of Mental Health, Veterans Affairs Greater Los Angeles Healthcare System, Los Angeles, CA, USA.
61
Institute for Community Medicine, University Medicine Greifswald, Greifswald, Germany.
62
Stanley Center for Psychiatric Research, The Broad Institute, Cambridge, MA, USA.
63
Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA, USA.
64
Psychiatry and Integrative Neurophysiology, VU University, Amsterdam UMC, Amsterdam, The Netherlands.
65
German Centre for Cardiovascular Research, Partner Site Greifswald, Greifswald, Germany.
66
Department of Psychology, University of Bath, Bath, UK.
67
Psychiatry and Behavioral Sciences, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
68
Radiology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
69
Queensland Brain Institute, University of Queensland, Brisbane, QLD, Australia.
70
Centre for Advanced Imaging, University of Queensland, Brisbane, QLD, Australia.
71
Seoul National University Hospital, Seoul, Republic of Korea.
72
Yeongeon Student Support Center, Seoul National University College of Medicine, Seoul, Republic of Korea.
73
Department of Computer Science and Electrical Engineering, University of Maryland, Baltimore County, MD, USA.
74
Department of Psychiatry and Behavioral Sciences, SUNY Upstate Medical University, Syracuse, NY, USA.
75
Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD, USA.
76
Norwegian Centre for Mental Disorders Research (NORMENT), Division of Mental Health & Addiction, Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
77
Department of Clinical Neuroscience, Centre for Psychiatric Research, Karolinska Institutet, Stockholm, Sweden.
78
Department of Psychiatric Research, Diakonhjemmet Hospital, Oslo, Norway.
79
Department of Psychiatry, Amsterdam UMC, Location VUmc, Amsterdam Neuroscience, Amsterdam, The Netherlands.
80
Department of Research & Innovation, GGZ InGeest, Amsterdam, The Netherlands.
81
University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
82
Psychiatry, Pediatrics, and Psychological Sciences, University of Vermont, Burlington, VT, USA.
83
Centre for Medical Image Computing (CMIC), Department of Medical Physics and Biomedical Engineering, University College London, London, UK.
84
Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway.
85
Provost and Senior Vice President, Western University of Health Sciences, Pomona, CA, USA.
86
Department of Radiology, Loma Linda University Medical Center, Loma Linda, CA, USA.
87
Institute of Psychology, Leiden University, Leiden, The Netherlands.
88
Department of Psychiatry, Leiden University Medical Center, Leiden, The Netherlands.
89
Leiden Institute for Brain and Cognition, Leiden, The Netherlands.
90
Department of Psychology, Yale University, New Haven, CT, USA.
91
Department of Psychology, University of California, Los Angeles, CA, USA.
92
Department of Cognitive Neuroscience, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, The Netherlands.
93
Cognitive Neuroscience Unit, School of Psychology, Deakin University, Burwood, VIC, Australia.
94
Department of Child and Adolescent Psychiatry/Psychology, Erasmus Medical Centre, Rotterdam, The Netherlands.
95
Department of Epidemiology, Erasmus Medical Centre, Rotterdam, The Netherlands.
96
Center for Cognitive Aging and Memory, University of Florida, Gainesville, FL, USA.
97
Clinical and Health Psychology, Gainesville, FL, USA.
98
Centre for Medical Image Computing (CMIC), Department of Computer Science, University College London, London, UK.
99
Dementia Research Centre, Institute of Neurology, University College London, London, UK.
100
Universite de Montreal, Centre de Recherche CHU Ste-Justine, Montreal, QC, Canada.
101
School of Psychology and Centre for Human Brain Health, University of Birmingham, Birmingham, UK.
102
Department of Neurology, University of Utah, Salt Lake City, UT, USA.
103
Psychiatry Neuroimaging Laboratory, Brigham & Women's Hospital, Harvard Medical School, Boston, MA, USA.
104
Social, Genetic & Developmental Psychiatry Centre, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK.
105
Department of Psychology, School of Arts and Social Sciences, City, University of London, London, UK.
106
Department of Neuroimaging, Institute of Psychology, Psychiatry and Neurosciences, King's College London, London, UK.
107
Division of Psychological and Social Medicine and Developmental Neurosciences, Faculty of Medicine, TU Dresden, Dresden, Germany.
108
Department of Rehabilitation and Movement Sciences, School of Health Professions, Rutgers Biomedical Health Sciences, Newark, NJ, USA.
109
Department of Psychiatry and Mental Health, University of Cape Town, Cape Town, South Africa.
110
SU/UCT MRC Unit on Risk & Resilience in Mental Disorders, University of Stellenbosch, Stellenbosch, South Africa.
111
Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
112
University of British Columbia, Vancouver, Canada.
113
Department of Psychiatry, Radboud University Medical Center, Nijmegen, The Netherlands.
114
Department of Psychiatry, University of Vermont, Burlington, VT, USA.
115
Department of Psychiatry, Boston Children's Hospital and Harvard Medical School, Boston, MA, USA.
116
Olin Neuropsychiatric Research Center, Institute of Living, Hartford, CT, USA.
117
Biomedical Engineering, Illinois Institute of Technology, Chicago, IL, USA.
118
Institute for Information Transmission Problems, Kharkevich Institute, Moscow, Russian Federation.
119
Turner Institute for Brain and Mental Health & School of Psychological Sciences, Monash University, Melbourne, VIC, Australia.
120
Department of Psychiatry & Neuropsychology, School for Mental Health and Neuroscience, Maastricht University, Maastricht, The Netherlands.
121
Genentech, Inc., South San Francisco, CA, USA.
122
Department of Psychology, Penn State University, University Park, PA, USA.
123
Social Life and Engineering Sciences Imaging Center, University Park, PA, USA.
124
Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA, USA.
125
Research and Scientific Institute of Pediatrics and Child Health, CCH RAS, Ministry of Science and Higher Education, Moscow, Russian Federation.
126
Department of Pediatrics, Michigan State University, East Lansing, MI, USA.
127
Institute for Quantitative Health Science and Engineering, East Lansing, MI, USA.
128
Department of Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
129
CBRAIN, Department of Child and Adolescent Psychiatry, Psychosomatics, and Psychotherapy, Ludwig-Maximilians-Universität München, Munich, Germany.
130
Stevens Neuroimaging and Informatics Institute, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
131
Chan Division of Occupational Science and Occupational Therapy, Los Angeles, CA, USA.
132
Center for Clinical Spectroscopy, Brigham and Women's Hospital, Boston, MA, USA.
133
Harvard Medical School, Boston, MA, USA.
134
National Center for PTSD at Boston VA Healthcare System, Boston, MA, USA.
135
Department of Psychiatry, Boston University School of Medicine, Boston, MA, USA.
136
Biomedical Genetics, Boston University School of Medicine, Boston, MA, USA.
137
School of Psychology, University of Auckland, Auckland, New Zealand.
138
Laboratory of Neuro Imaging, Mark and Mary Stevens Neuroimaging and Informatics Institute, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
139
Department of Psychiatry and Human Behavior, University of California, Irvine, Irvine, CA, USA.
140
Mind Research Network, Albuquerque, NM, USA.
141
Psychiatry, San Diego, CA, USA.
142
The Kavli Foundation, Los Angeles, CA, USA.
143
Department of Psychosis Studies, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK.
144
Department of Psychiatry, Duke University School of Medicine, Durham, NC, USA.
145
Mental Illness Research Education and Clinical Center, Durham VA Medical Center, Durham, NC, USA.
146
Experimental Clinical & Health Psychology, Ghent University, Ghent, Belgium.
147
Department of Personality, Psychological Assessment and Treatment, University of Deusto, Bilbao, Spain.
148
Radiology and Biomedical Imaging, San Francisco, CA, USA.
149
Department of Pediatrics, Russian National Research Medical University MoH RF, Moscow, Russian Federation.
150
Department of Psychology, Norwegian University of Science and Technology, Trondheim, Norway.
151
Department of Physical Medicine and Rehabilitation, St. Olavs Hospital, Trondheim University Hospital, Trondheim, Norway.
152
Biological Sciences, Purdue University, West Lafayette, IN, USA.
153
National Institute of Mental Health Intramural Research Program, Bethesda, MD, USA.
154
Department of Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia.
155
Department of Neurodegenerative Disease, UCL Queen Square Institute of Neurology, London, UK.
156
Max Planck Institute of Psychiatry, Munich, Germany.
157
Centre for Youth Mental Health, The University of Melbourne, Melbourne, VIC, Australia.
158
Department of Psychiatry and Psychotherapy, Charite, Humboldt University, Berlin, Germany.
159
Department of Radiology, Keck School of Medicine of USC, University of Southern California, Los Angeles, CA, USA.
160
Department of Clinical and Experimental Epilepsy, University College London, London, UK.
161
Chalfont Centre for Epilepsy, Chalfont St Peter, UK.
162
Department of Medical Genetics, Oslo University Hospital, Oslo, Norway.
163
Department of Psychiatry & Neuroscience Institute, SA MRC Unit on Risk & Resilience in Mental Disorders, Cape Town, South Africa.
164
Department of Genetics & UNC Neuroscience Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
165
Institute of Medical Science and Technology, Shahid Beheshti University, Tehran, I. R., Iran.
166
Department of Neurology, TBI and Concussion Center, Salt Lake City, UT, USA.
167
Missouri Institute of Mental Health, Berkeley, MO, USA.
168
Psychology Department & Neuroscience Institute, Georgia State University, Atlanta, GA, USA.
169
Clinical Translational Neuroscience Laboratory, Department of Psychiatry and Human Behavior, University of California Irvine, Irvine, CA, USA.
170
Center for the Neurobiology of Learning and Memory, University of California, Irvine, Irvine, CA, USA.
171
Donders Centre for Cognitive Neuroimaging, Radboud University Medical Centre, Nijmegen, The Netherlands.
172
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.
173
Molecular and Cellular Therapeutics, Royal College of Surgeons in Ireland, Dublin, Ireland.
174
Research and Early Development, Biogen Inc, Cambridge, MA, USA.
175
VA Salt Lake City Healthcare System, Salt Lake City, UT, USA.
176
Department of Physical Medicine and Rehabilitation, Baylor College of Medicine, Houston, TX, USA.
177
Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
178
Skolkovo Institute of Science and Technology, Moscow, Russian Federation.

Abstract

This review summarizes the last decade of work by the ENIGMA (Enhancing NeuroImaging Genetics through Meta Analysis) Consortium, a global alliance of over 1400 scientists across 43 countries, studying the human brain in health and disease. Building on large-scale genetic studies that discovered the first robustly replicated genetic loci associated with brain metrics, ENIGMA has diversified into over 50 working groups (WGs), pooling worldwide data and expertise to answer fundamental questions in neuroscience, psychiatry, neurology, and genetics. Most ENIGMA WGs focus on specific psychiatric and neurological conditions, other WGs study normal variation due to sex and gender differences, or development and aging; still other WGs develop methodological pipelines and tools to facilitate harmonized analyses of "big data" (i.e., genetic and epigenetic data, multimodal MRI, and electroencephalography data). These international efforts have yielded the largest neuroimaging studies to date in schizophrenia, bipolar disorder, major depressive disorder, post-traumatic stress disorder, substance use disorders, obsessive-compulsive disorder, attention-deficit/hyperactivity disorder, autism spectrum disorders, epilepsy, and 22q11.2 deletion syndrome. More recent ENIGMA WGs have formed to study anxiety disorders, suicidal thoughts and behavior, sleep and insomnia, eating disorders, irritability, brain injury, antisocial personality and conduct disorder, and dissociative identity disorder. Here, we summarize the first decade of ENIGMA's activities and ongoing projects, and describe the successes and challenges encountered along the way. We highlight the advantages of collaborative large-scale coordinated data analyses for testing reproducibility and robustness of findings, offering the opportunity to identify brain systems involved in clinical syndromes across diverse samples and associated genetic, environmental, demographic, cognitive, and psychosocial factors.

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