Consortium neuroscience of attention deficit/hyperactivity disorder and autism spectrum disorder: The ENIGMA adventure

Martine Hoogman, Daan van Rooij, Marieke Klein, Premika Boedhoe, Iva Ilioska, Ting Li, Yash Patel, Merel C. Postema, Yanli Zhang-James, Evdokia Anagnostou, Celso Arango, Guillaume Auzias, Tobias Banaschewski, Claiton H.D. Bau, Marlene Behrmann, Mark A. Bellgrove, Daniel Brandeis, Silvia Brem, Geraldo F. Busatto, Sara CalderoniRosa Calvo, Francisco X. Castellanos, David Coghill, Annette Conzelmann, Eileen Daly, Christine Deruelle, Ilan Dinstein, Sarah Durston, Christine Ecker, Stefan Ehrlich, Jeffery N. Epstein, Damien A. Fair, Jacqueline Fitzgerald, Christine M. Freitag, Thomas Frodl, Louise Gallagher, Eugenio H. Grevet, Jan Haavik, Pieter J. Hoekstra, Joost Janssen, Georgii Karkashadze, Joseph A. King, Kerstin Konrad, Jonna Kuntsi, Luisa Lazaro, Jason P. Lerch, Klaus Peter Lesch, Mario R. Louza, Beatriz Luna, Paulo Mattos, Jane McGrath, Filippo Muratori, Clodagh Murphy, Joel T. Nigg, Eileen Oberwelland-Weiss, Ruth L. O'Gorman Tuura, Kirsten O'Hearn, Jaap Oosterlaan, Mara Parellada, Paul Pauli, Kerstin J. Plessen, J. Antoni Ramos-Quiroga, Andreas Reif, Liesbeth Reneman, Alessandra Retico, Pedro G.P. Rosa, Katya Rubia, Philip Shaw, Tim J. Silk, Leanne Tamm, Oscar Vilarroya, Susanne Walitza, Neda Jahanshad, Stephen V. Faraone, Clyde Francks, Odile A. van den Heuvel, Tomas Paus, Paul M. Thompson, Jan K. Buitelaar, Barbara Franke

Research output: Contribution to journalReview articlepeer-review

41 Scopus citations


Neuroimaging has been extensively used to study brain structure and function in individuals with attention deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) over the past decades. Two of the main shortcomings of the neuroimaging literature of these disorders are the small sample sizes employed and the heterogeneity of methods used. In 2013 and 2014, the ENIGMA-ADHD and ENIGMA-ASD working groups were respectively, founded with a common goal to address these limitations. Here, we provide a narrative review of the thus far completed and still ongoing projects of these working groups. Due to an implicitly hierarchical psychiatric diagnostic classification system, the fields of ADHD and ASD have developed largely in isolation, despite the considerable overlap in the occurrence of the disorders. The collaboration between the ENIGMA-ADHD and -ASD working groups seeks to bring the neuroimaging efforts of the two disorders closer together. The outcomes of case–control studies of subcortical and cortical structures showed that subcortical volumes are similarly affected in ASD and ADHD, albeit with small effect sizes. Cortical analyses identified unique differences in each disorder, but also considerable overlap between the two, specifically in cortical thickness. Ongoing work is examining alternative research questions, such as brain laterality, prediction of case–control status, and anatomical heterogeneity. In brief, great strides have been made toward fulfilling the aims of the ENIGMA collaborations, while new ideas and follow-up analyses continue that include more imaging modalities (diffusion MRI and resting-state functional MRI), collaborations with other large databases, and samples with dual diagnoses.

Original languageEnglish (US)
Pages (from-to)37-55
Number of pages19
JournalHuman Brain Mapping
Issue number1
Early online dateMay 18 2020
StatePublished - Jan 2022
Externally publishedYes

Bibliographical note

Funding Information:
Martine Hoogman is supported by a personal Veni grant of the Netherlands Organization for Scientific Research (NWO, grant number 91619115). Odile A. van den Heuvel is supported by a personal VIDI grant of the Netherlands Organization for Scientific Research (NWO/ZonMw, number 91717306). This work has further benefited from grants for the NeuroIMAGE study which was supported by NIH Grant R01MH62873 (to Stephen V. Faraone), NWO Large Investment Grant 1750102007010 (to Jan Buitelaar), ZonMW grant 60‐60600‐97‐193, NWO grants 056‐13‐015 and 433‐09‐242, and matching grants from Radboud University Nijmegen Medical Center, University Medical Center Groningen and Accare, and Vrije Universiteit Amsterdam. This also included support from the European Community's Seventh Framework Programme (FP7/2007‐2013) under grant agreement number 278948 (TACTICS), 602805 (Aggressotype), 603016 (MATRICS), and 602450 (Imagemend), and the Innovation Medicine Initiative grants 115300 (EU‐AIMS) and 777394 (AIMS‐2‐TRIALS). Support was also received from the Dutch National Science Agenda for the NWA NeurolabNL project (grant 400 17 602). The first and senior authors would like to acknowledge the Cognomics Initiative, a joint initiative by researchers of the Donders Centre for Cognitive Neuroimaging, the Human Genetics and Cognitive Neuroscience departments of the Radboud University Medical Center, and the Max Planck Institute for Psycholinguistics in Nijmegen. The Cognomics Initiative has received support from the participating departments and centres and from external grants, that is, the Biobanking and Biomolecular Resources Research Infrastructure (Netherlands) (BBMRI‐NL), the Hersenstichting Nederland, the Netherlands Organization for Scientific Research (NWO), and the European Community's Seventh Framework Programme (FP7/2007–2013) under grant agreements n° 602450 (IMAGEMEND). In addition, the work was supported by a grant for the ENIGMA Consortium (grant number U54 EB020403) from the BD2K Initiative of a cross‐NIH partnership. The POND (Province of Ontario Neurodevelopmental Disorders) data collection was supported by the grant IDS‐I l‐02 (to Evdokia Anagnostou, Jason Lerch) from the Ontario Brain Institute, as well as CIHR support from grants CIHR‐106582, CIHR‐142379 (to Margot Taylor). Initial support for the ENIGMA ADHD and ASD working groups was provided by the U.S. National Institutes of Health Big Data to Knowledge Program (BD2K), under grant U54 EB020403. Joel T. Nigg is supported by an NIH grant R01 MH115357. We would like to thank all consortium authors that are not named co‐authors on this article: Sara Ambrosino, Anatoly Anikin, Philip Asherson, Cibele Bandeira, Alexandr Baranov, Sarah Baumeister, Ramona Baur‐Streubel, Joseph Biederman, Janita Bralten, Ivanei Bramati, Anna Calvo, Mara Cercignani, Tiffany Chaim‐Avancini, Kaylita Chantiluke, Anastasia Christakou, Ana Cubillo, Renata Cupertino, Anders Dale, Patrick de Zeeuw, Alysa Doyle, Eric Earl, Thomas Ethofer, Andreas Fallgatter, Matt Gabel, Tinatin Gogberashvili, Neil Harrison, Catharina Hartman, Dirk Heslenfeld, Sarah Hohmann, Marie Høvik, Terry Jernigan, Dmitry Kapilushniy, Bernd Kardatzki, Clare Kelly, Gregor Kohls, Sara Lera‐Miguel, Astri Lundervold, Charles Malpas, Hazel McCarthy, Mitul Mehta, Leyla Namazova‐Baranova, Rosa Nicolau, Stephanie Novotny, Bob Oranje, Yannis Paloyelis, Felipe Picon, Anouk Schrantee, Lena Schwarz, Lizanne Schweren, Jochen Seitz, Norbert Skokauskas, Juan Carlos Soliva Vila, Anastasia Solovieva, Michael Stevens, Gustavo Sudre, Fernanda Tovar‐Moll, Theo van Erp, Alasdair Vance, Yolanda Vives‐Gilabert, Georg von Polier, Yuliya Yoncheva, Marcus Zanetti, Georg Ziegler, and Kathrin Zierhut.

Funding Information:
was supported in part by a research grant from Biogen, Inc. (Boston, USA) for research unrelated to this manuscript. received speaker honorarium from Benecke. served in an advisory or consultancy role for Lilly, Medice, Novartis, Oxford outcomes, Shire and Viforpharma. He received conference support or speaker's fee by Janssen McNeil, Lilly, Medice, Novartis, Shire and Sunovian. He is/has been involved in clinical trials conducted by Lilly & Shire. The present work is unrelated to the above grants and relationships. has given talks at educational events sponsored by and Medicine; all funds are received by King's College London and used for studies of ADHD. was on the speakers' bureau and/or acted as consultant for Janssen‐Cilag, Novartis, and Shire in the previous 5 years; he also received travel awards to participate in scientific meetings from those companies. The ADHD outpatient program (Grupo de Estudos do Déficit de Atenção/Institute of Psychiatry) chaired by Dr. Mattos has also received research support from Novartis and Shire.The funding sources had no role in the design and conduct of the study; collection, management, analysis, or interpretation of the data; or preparation, review, or approval of the manuscript. served in an advisory or consultancy role for Lundbeck, Medice, Neurim Pharmaceuticals, Oberberg GmbH, Shire, and Infectopharm. He received conference support or speaker’s fee by Lilly, Medice, and Shire. He received royalities from Hogrefe, Kohlhammer, CIP Medien, Oxford University Press; the present work is unrelated to these relationships. received a grant from Takeda pharmaceuticals for another project. has received speaker fees from Lilly, Novartis and Janssen Cilag. , received income, potential income, travel expenses continuing education support and/or research support from Tris, Otsuka, Arbor, Ironshore, Shire, Akili Interactive Labs, VAYA, Ironshore, Sunovion, Supernus and Genomind. With his institution, he has US patent US20130217707 A1 for the use of sodium‐hydrogen exchange inhibitors in the treatment of ADHD. received speaking fees from Medice, Lilly and Shire. was on the speakers' bureau and/or acted as a consultant for Eli‐Lilly, Janssen‐Cilag, Novartis, Shire, Lundbeck, Almirall, Braingaze, Sincrolab, Medice and Rubió in the last 5 years. He also received travel awards (air tickets + hotel) for taking part in psychiatric meetings from Janssen‐Cilag, Medice, Rubió, Shire, and Eli‐ Lilly. The Department of Psychiatry chaired by him received unrestricted educational and research support from the following companies in the last 5 years: Eli‐Lilly, Lundbeck, Janssen‐ Cilag, Actelion, Shire, Ferrer, Oryzon, Roche, Psious, and Rubió. served as a speaker for Eli Lilly and received research support from Medice, and travel support from Shire, all outside the submitted work. received a research grant from Shire and was part of the advisory board of Shire. has been in the past 3 years a consultant to/member of advisory board of / and/or speaker for Janssen Cilag BV, Eli Lilly, Medice, Shire, Roche, and Servier. He is not an employee of any of these companies, and not a stock shareholder of any of these companies. He has no other financial or material support, including expert testimony, patents, royalties. has received educational speaking fees from Medice. has received lecture honoraria from Eli‐Lilly, Opopharma in the last 5 years and her outside professional activities and interests are declared under the link of the University of Zurich . serves as an unpaid scientific consultant for an EU‐funded neurofeedback trial. received payment for the authorship of the article and speaker fees from Sanofi and from Pikfarma. has served as a consultant or advisory board member for Roche and Takeda; she has received funding from the Alva Foundation, Autism Speaks, Brain Canada, the Canadian Institutes of Health Research, the Department of Defense, the National Centers of Excellence, NIH, the Ontario Brain Institute, the Physicians' Services Incorporated (PSI) Foundation, Sanofi‐Aventis, and SynapDx, as well as in‐kind research support from AMO Pharma; she receives royalties from American Psychiatric Press and Springer and an editorial honorarium from Wiley. Her contribution is on behalf of the POND network. has served as a consultant for or received honoraria or grants from Acadia, Abbott, Amgen, CIBERSAM, Fundación Alicia Koplowitz, Instituto de Salud Carlos III, Janssen‐Cilag, Lundbeck, Merck, Instituto de Salud Carlos III (co‐financed by the European Regional Development Fund “A way of making Europe,” CIBERSAM, the Madrid Regional Government [S2010/BMD‐2422 AGES], the European Union Structural Funds, and the European Union Seventh Framework Programmeunder grant agreements FP7‐HEALTH‐2009‐2.2.1‐2‐241909, FP7‐HEALTH‐2009‐2.2.1‐3‐242114, FP7‐HEALTH‐2013‐2.2.1‐2‐603196, and FP7‐HEALTH‐2013‐2.2.1‐2‐602478), Otsuka, Pfizer, Roche, Servier, Shire, Takeda, and Schering‐Plow. has served as a consultant for Desitin regarding issues on ASD. Paul M. Thompson Odile A. van den Heuvel David Coghill Jonna Kuntsi Paulo Mattos Tobias Banaschewski Katya Rubia Jan Haavik Stephen V. Faraone Kerstin Konrad Josep‐Antoni Ramos‐Quiroga Josep‐Antoni Ramos‐Quiroga Klaus‐Peter Lesch Pieter Hoekstra Jan Buitelaar Barbara Franke Susanne Walitza Daniel Brandeis Georgii Karkashadze Dr. Anagnostou Dr. Arango Dr. Freitag

Funding Information:
Dutch National Science Agenda, Grant/Award Number: 400 17 602; Innovation Medicine Initiatives, Grant/Award Numbers: 115300, 777394; National Institute of Mental Health, Grant/Award Numbers: R01MH62873, R01MH115357; Nederlandse Organisatie voor Wetenschappelijk Onderzoek, Grant/Award Numbers: 056‐13‐015, 1750102007010, 433‐09‐242, 91619115, 91717306; Seventh Framework Programme, Grant/Award Numbers: 278948, 602805, 603016 602450; U.S. National Institutes of Health Big Data to Knowledge Program, Grant/Award Number: U54 EB020403; ZonMw, Grant/Award Number: 60‐60600‐97‐193 Funding information

Publisher Copyright:
© 2020 The Authors. Human Brain Mapping published by Wiley Periodicals, Inc.


  • ADHD
  • ASD
  • cortex
  • neuroimaging
  • subcortical volumes

PubMed: MeSH publication types

  • Journal Article
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review


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