Subcortical brain volume, regional cortical thickness, and cortical surface area across disorders: findings from the ENIGMA ADHD, ASD, and OCD working groups
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OBJECTIVE: Attention deficit hyperactivity disorder (ADHD), autism spectrum disorder (ASD), and obsessive-compulsive disorder (OCD) are common neurodevelopmental disorders that frequently co-occur. The authors sought to directly compare these disorders using structural brain imaging data from ENIGMA consortium data. METHODS: -weighted whole-brain MRI data from healthy control subjects (N=5,827) and from patients with ADHD (N=2,271), ASD (N=1,777), and OCD (N=2,323) from 151 cohorts worldwide were analyzed using standardized processing protocols. The authors examined subcortical volume, cortical thickness, and cortical surface area differences within a mega-analytical framework, pooling measures extracted from each cohort. Analyses were performed separately for children, adolescents, and adults, using linear mixed-effects models adjusting for age, sex, and site (and intracranial volume for subcortical and surface area measures). RESULTS: No shared differences were found among all three disorders, and shared differences between any two disorders did not survive correction for multiple comparisons. Children with ADHD compared with those with OCD had smaller hippocampal volumes, possibly influenced by IQ. Children and adolescents with ADHD also had smaller intracranial volume than control subjects and those with OCD or ASD. Adults with ASD showed thicker frontal cortices compared with adult control subjects and other clinical groups. No OCD-specific differences were observed across different age groups and surface area differences among all disorders in childhood and adulthood. CONCLUSIONS: The study findings suggest robust but subtle differences across different age groups among ADHD, ASD, and OCD. ADHD-specific intracranial volume and hippocampal differences in children and adolescents, and ASD-specific cortical thickness differences in the frontal cortex in adults, support previous work emphasizing structural brain differences in these disorders.
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ADHD participants have smaller hippocampus volume relative to OCD and smaller intracranial volume relative to ASD and OCD.
“An analysis of structural magnetic resonance imaging (MRI) data from 48 cohorts with a total of over 12,000 participants showed that ADHD participants had smaller hippocampus volume relative to OCD which was related to IQ differences and smaller intracranial volume relative to ASD and OCD patients (Boedhoe et al., 2020).”
From The World Federation of ADHD International Consensus Statement: 208 Evidence-based conclusions about the disorder (2021) · cites this paper as Boedhoe et al., 2020
The Results (Disease-specific subcortical and cortical differences) report smaller hippocampal volume in children with ADHD than in children with OCD, and smaller intracranial volume in children and adolescents with ADHD than in those with ASD or OCD. The Discussion says IQ differences may explain the hippocampal finding; it does not establish that relationship. The citing sentence omits the age limits and says 48 cohorts, whereas the Methods report 151 cohorts. (LLM, conf=0.89)
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- Authors
- Boedhoe, P. S. W., van Rooij, D., Hoogman, M., Twisk, J. W. R., Schmaal, L., Abe, Y., Alonso, P., Ameis, S. H., Anikin, A., Anticevic, A., Arango, C., Arnold, P. D., Asherson, P., Assogna, F., Auzias, G., Banaschewski, T., Baranov, A., Batistuzzo, M. C., Baumeister, S., Baur-Streubel, R., Behrmann, M., Bellgrove, M. A., Benedetti, F., Beucke, J. C., Biederman, J., Bollettini, I., Bose, A., Bralten, J., Bramati, I. E., Brandeis, D., Brem, S., Brennan, B. P., Busatto, G. F., Calderoni, S., Calvo, A., Calvo, R., Castellanos, F. X., Cercignani, M., Chaim-Avancini, T. M., Chantiluke, K. C., Cheng, Y., Cho, K. I. K., Christakou, A., Coghill, D., Conzelmann, A., Cubillo, A. I., Dale, A. M., Dallaspezia, S., Daly, E., Denys, D., Deruelle, C., Di Martino, A., Dinstein, I., Doyle, A. E., Durston, S., Earl, E. A., Ecker, C., Ehrlich, S., Ely, B. A., Epstein, J. N., Ethofer, T., Fair, D. A., Fallgatter, A. J., Faraone, S. V., Fedor, J., Feng, X., Feusner, J. D., Fitzgerald, J., Fitzgerald, K. D., Fouche, J.-P., Freitag, C. M., Fridgeirsson, E. A., Frodl, T., Gabel, M. C., Gallagher, L., Gogberashvili, T., Gori, I., Gruner, P., Gürsel, D. A., Haar, S., Haavik, J., Hall, G. B., Harrison, N. A., Hartman, C. A., Heslenfeld, D. J., Hirano, Y., Hoekstra, P. J., Hoexter, M. Q., Hohmann, S., Høvik, M. F., Hu, H., Huyser, C., Jahanshad, N., Jalbrzikowski, M., James, A., Janssen, J., Jaspers-Fayer, F., Jernigan, T. L., Kapilushniy, D., Kardatzki, B., Karkashadze, G., Kathmann, N., Kaufmann, C., Kelly, C., Khadka, S., King, J. A., Koch, K., Kohls, G., Konrad, K., Kuno, M., Kuntsi, J., Kvale, G., Kwon, J. S., Lázaro, L., Lera-Miguel, S., Lesch, K.-P., Hoekstra, L., Liu, Y., Lochner, C., Louza, M. R., Luna, B., Lundervold, A. J., Malpas, C. B., Marques, P., Marsh, R., Martínez-Zalacaín, I., Mataix-Cols, D., Mattos, P., McCarthy, H., McGrath, J., Mehta, M. A., Menchón, J. M., Mennes, M., Martinho, M. M., Moreira, P. S., Morer, A., Morgado, P., Muratori, F., Murphy, C. M., Murphy, D. G. M., Nakagawa, A., Nakamae, T., Nakao, T., Namazova-Baranova, L., Narayanaswamy, J. C., Nicolau, R., Nigg, J. T., Novotny, S. E., Nurmi, E. L., Weiss, E. O., O’Gorman Tuura, R. L., O’Hearn, K., O’Neill, J., Oosterlaan, J., Oranje, B., Paloyelis, Y., Parellada, M., Pauli, P., Perriello, C., Piacentini, J., Piras, F., Piras, F., Plessen, K. J., Puig, O., Ramos-Quiroga, J. A., Reddy, Y. C. J., Reif, A., Reneman, L., Retico, A., Rosa, P. G. P., Rubia, K., Rus, O. G., Sakai, Y., Schrantee, A., Schwarz, L., Schweren, L. J. S., Seitz, J., Shaw, P., Shook, D., Silk, T. J., Simpson, H. B., Skokauskas, N., Soliva Vila, J. C., Solovieva, A., Soreni, N., Soriano-Mas, C., Spalletta, G., Stern, E. R., Stevens, M. C., Stewart, S. E., Sudre, G., Szeszko, P. R., Tamm, L., Taylor, M. J., Tolin, D. F., Tosetti, M., Tovar-Moll, F., Tsuchiyagaito, A., van Erp, T. G. M., van Wingen, G. A., Vance, A., Venkatasubramanian, G., Vilarroya, O., Vives-Gilabert, Y., von Polier, G. G., Walitza, S., Wallace, G. L., Wang, Z., Wolfers, T., Yoncheva, Y. N., Yun, J.-Y., Zanetti, M. V., Zhou, F., Ziegler, G. C., Zierhut, K. C., Zwiers, M. P., the ENIGMA ADHD working group, the ENIGMA ASD working group, the ENIGMA OCD working group, Thompson, P. M., Stein, D. J., Buitelaar, J., Franke, B., & van den Heuvel, O. A.
- Affiliations
- The full list of authors in the ENIGMA working groups, author affiliations, author disclosures, and acknowledgments are provided in .
- ORCID
- Hoogman, Martine
- Twisk, Jos W.R.
- Schmaal, Lianne
- Abe, Yoshinari
- Alonso, Pino
- Ameis, Stephanie H.
- Anticevic, Alan
- Arango, Celso
- Arnold, Paul D.
- Asherson, Philip
- Assogna, Francesca
- Auzias, Guillaume
- Banaschewski, Tobias
- Batistuzzo, Marcelo C.
- Baumeister, Sarah
- Behrmann, Marlene
- Bellgrove, Mark A.
- Benedetti, Francesco
- Beucke, Jan C.
- Biederman, Joseph
- Bollettini, Irene
- Bose, Anushree
- Bralten, Janita
- Bramati, Ivanei E.
- Brem, Silvia
- Brennan, Brian P.
- Busatto, Geraldo F.
- Calderoni, Sara
- Calvo, Rosa
- Castellanos, Francisco X.
- Cercignani, Mara
- Chantiluke, Kaylita C.
- Cheng, Yuqi
- Cho, Kang Ik K.
- Christakou, Anastasia
- Coghill, David
- Conzelmann, Annette
- Cubillo, Ana I.
- Dale, Anders M.
- Dallaspezia, Sara
- Daly, Eileen
- Denys, Damiaan
- Deruelle, Christine
- Dinstein, Ilan
- Doyle, Alysa E.
- Earl, Eric A.
- Ecker, Christine
- Ehrlich, Stefan
- Ely, Benjamin A.
- Epstein, Jeffrey N.
- Ethofer, Thomas
- Fair, Damien A.
- Fallgatter, Andreas J.
- Faraone, Stephen V.
- Fedor, Jennifer
- Feusner, Jamie D.
- Fitzgerald, Kate D.
- Freitag, Christine M.
- Fridgeirsson, Egill A.
- Frodl, Thomas
- Gabel, Matt C.
- Gallagher, Louise
- Gogberashvili, Tinatin
- Gori, Ilaria
- Gruner, Patricia
- Haar, Shlomi
- Haavik, Jan
- Hall, Geoffrey B.
- Harrison, Neil A.
- Hartman, Catharina A.
- Hirano, Yoshiyuki
- Hoekstra, Pieter J.
- Hoexter, Marcelo Q.
- Hohmann, Sarah
- Hu, Hao
- Huyser, Chaim
- Jahanshad, Neda
- Jalbrzikowski, Maria
- James, Anthony
- Janssen, Joost
- Jernigan, Terry L.
- Kathmann, Norbert
- Kaufmann, Christian
- Kelly, Clare
- King, Joseph A.
- Koch, Kathrin
- Kohls, Gregor
- Konrad, Kerstin
- Kuno, Masaru
- Kuntsi, Jonna
- Kvale, Gerd
- Kwon, Jun Soo
- Lázaro, Luisa
- Lesch, Klaus-Peter
- Liu, Yanni
- Lundervold, Astri J.
- Malpas, Charles B.
- Marques, Paulo
- Marsh, Rachel
- McGrath, Jane
- Mehta, Mitul A.
- Menchón, José M.
- Mennes, Maarten
- Moreira, Pedro S.
- Morgado, Pedro
- Muratori, Filippo
- Murphy, Declan G.M.
- Nakamae, Takashi
- Nakao, Tomohiro
- Namazova-Baranova, Leyla
- Narayanaswamy, Janardhanan C.
- Nicolau, Rosa
- Nigg, Joel T.
- Nurmi, Erika L.
- O’Hearn, Kirsten
- O’Neill, Joseph
- Oosterlaan, Jaap
- Oranje, Bob
- Paloyelis, Yannis
- Parellada, Mara
- Pauli, Paul
- Perriello, Chris
- Piacentini, John
- Piras, Fabrizio
- Piras, Federica
- Plessen, Kerstin J.
- Puig, Olga
- Reddy, Y.C. Janardhan
- Reif, Andreas
- Reneman, Liesbeth
- Retico, Alessandra
- Rubia, Katya
- Sakai, Yuki
- Schrantee, Anouk
- Schweren, Lizanne J.S.
- Seitz, Jochen
- Shaw, Philip
- Simpson, H. Blair
- Skokauskas, Norbert
- Soreni, Noam
- Spalletta, Gianfranco
- Stern, Emily R.
- Stevens, Michael C.
- Stewart, S. Evelyn
- Sudre, Gustavo
- Szeszko, Philip R.
- Tamm, Leanne
- Taylor, Margot J.
- Tolin, David F.
- Tosetti, Michela
- Tovar-Moll, Fernanda
- Tsuchiyagaito, Aki
- Vance, Alasdair
- Venkatasubramanian, Ganesan
- Walitza, Susanne
- Wallace, Gregory L.
- Wang, Zhen
- Wolfers, Thomas
- Yoncheva, Yuliya N.
- Yun, Je-Yeon
- Zanetti, Marcus V.
- Zhou, Fengfeng
- Ziegler, Georg C.
- Zwiers, Marcel P.
- Thompson, Paul M.
- Stein, Dan J.
- Buitelaar, Jan
- Franke, Barbara
- Venue
- American Journal of Psychiatry
- Published
- 2020-09-01
- Volume
- 177
- Issue
- 9
- Pages
- 834-843
- ISSN
- 0002-953X (ISSN-L)
- 1535-7228
- PMC
- PMC8296070
- OpenAlex
- W3034761030
- Cited by
- 201
- References
- 43
- Citations by year
- 2026: 22 · 2025: 30 · 2024: 39 · 2023: 33 · 2022: 29 · 2021: 38 · 2020: 10
- FWCI
- 20.06
- Type
- journal article
- Language
- en
- Open access
- Licence
- other-oa
- Locations
- American Journal of Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Research Publications (Maastricht University) (publishedVersion, other-oa)
- Discovery Research Portal (University of Dundee) (publishedVersion, other-oa)
- Research Portal (King's College London) (publishedVersion, other-oa)
- Amsterdam UMC (VU Amsterdam) - Institutional Repository (publishedVersion)
- CentAUR (University of Reading) (acceptedVersion)
- ORCA Online Research @Cardiff (Cardiff University) (acceptedVersion)
- Zurich Open Repository and Archive (University of Zurich) (acceptedVersion)
- PubMed Central (acceptedVersion)
- CINECA IRIS Institutial research information system (University of Pisa) (submittedVersion, other-oa)
- eScholarship (California Digital Library) (submittedVersion)
- Minerva Access (University of Melbourne) (submittedVersion, other-oa)
- Radboud Repository (Radboud University) (submittedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- HAL AMU (submittedVersion, other-oa)
- Utrecht University Repository (Utrecht University) (submittedVersion, other-oa)
- Figshare (submittedVersion)
- IRIS (submittedVersion)
- Archivio Istituzionale della Ricerca - Università Vita-Salute San Raffaele (submittedVersion)
- mediaTUM – the media and publications repository of the Technical University Munich (Technical University Munich) (submittedVersion)
- Pure Amsterdam UMC (submittedVersion)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion, other-oa)
- SERVAL (Université de Lausanne) (submittedVersion)
- Zurich Open Repository and Archive (University of Zurich) (submittedVersion)
- Radboud Repository (Radboud University) (submittedVersion, other-oa)
- Zurich Open Repository and Archive (University of Zurich)
- Funders
- National Science Foundation (FP7/2007-2013)
- U.S. Department of Defense
- Autism Speaks
- Dana Foundation
- Eli Lilly and Company
- Sanofi
- Massachusetts General Hospital
- Yale University
- Oregon Health and Science University
- Leon Levy Foundation (R01MH083246)
- George Washington University
- Cincinnati Children's Hospital Medical Center
- Stiftelsen Kristian Gerhard Jebsen
- Johns Hopkins University
- University of Cincinnati
- Fundació la Marató de TV3 (01/2010, 091710)
- Ontario Brain Institute
- Fondation Brain Canada
- Japan Agency for Medical Research and Development (JP18dm0307002)
- National Alliance for Research on Schizophrenia and Depression (667302, R01MH085328, 728018, 602805, R01MH083246, U01MH099059)
- Wellcome Trust
- Children’s Hospital of Wisconsin Research Institute
- Children's Hospital Foundation
- BC Children's Hospital
- Alva Foundation
- Murdoch Children's Research Institute (1065895)
- Royal Children's Hospital Foundation
- National Institute of Mental Health and Neurosciences
- Amsterdam University Medical Centers
- Instituto D'Or de Pesquisa e Ensino
- York University
- Michael Smith Health Research BC
- Tenovus
- King's College London (278948)
- University of Oxford
- European Commission (EU-FP7, 643051, 602450, 2007–2013, Eat2beNICE, FP7 2007-2013, 278948, HORIZON2020, 728018, FP7/2007, 667302, 260576, 327340, 602805)
- National Research Foundation
- Department of Biotechnology, Ministry of Science and Technology, India (BT/06/IYBA/2012., 500236/ Z/11/Z)
- Department of Science and Technology, Ministry of Science and Technology, India (IFA 12-LSBM 26, /PR13334/Med/30/259/2009, SR/S0/HS/0016/2011, IFA-12)
- Deutsche Forschungsgemeinschaft (RE1632/5‐1, TRR‐58, KFO125, 602805, FP7/2007–2013, Eat2beNICE, 728018, 667302, ET 112/5-1, SFB TRR 58)
- Ministry of Education, Culture, Sports, Science and Technology (25461732, 22591262, 16K10253)
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (FP7/2007-2013, 32362, 130237, 136249, 113601)
- University of Melbourne
- National Natural Science Foundation of China (13dz2260500, FP7/2007-2013, 81371340, FP7/2007, R01MH083246)
- ZonMw (60-60600-97-193, 917.15.318, 056-13-015, 60600, 433-09-242)
- Universiteit van Amsterdam (11.32050.26)
- Radboud Universiteit
- Vrije Universiteit Amsterdam (433-09-242, FP7/2007-2013, 278948, 056-13-015)
- Seoul National University (FP7/2007-2013)
- Generalitat de Catalunya (2017-SGR)
- Ministero della Salute (RC13-14-15-16-17-18A)
- Nederlandse Organisatie voor Wetenschappelijk Onderzoek (602805, 433‐09‐242, 175.010.2007.010, FP7 2007-2013, 05613015, 602450, 728018, 916.86.036, NWO/ZonMW Vidi 917.15.318, 278948, 60600, 667302, R01MH083246, 917-15-318, 60-60600-97-193)
- Accare
- Ministerio de Economía y Competitividad (PI12/01139, PI14/, PI14/00419, PI16/, FI17/00294, SAF2012‐32362, PI040829, PI13/01958, PI16/00889, PI12/, CPII16/00048, SAF2012)
- Provincial Health Services Authority
- Conselho Nacional de Desenvolvimento Científico e Tecnológico (01/2010)
- Shire
- Stavros Niarchos Foundation (R01MH083246)
- State Government of Victoria
- Shanghai Jiao Tong University
- Universitetet i Bergen
- Universitair Medisch Centrum Groningen
- Universidade de São Paulo
- Hospital for Sick Children
- Radboud Universitair Medisch Centrum
- Universität Zürich
- Centro de Investigación Biomédica en Red de Salud Mental
- European College of Neuropsychopharmacology
- Universidade Federal do Rio de Janeiro
- Chiba University
- The Wellcome Trust DBT India Alliance (500236/Z/11/Z)
- Universitat Autònoma de Barcelona
- H. Lundbeck A/S
- Collier Charitable Fund (384419, 569533)
- National Institutes of Health (5r01mh099064-05, 1065895, FP7/2007-2013, 5k23mh104515-05, 1008522, 1750102007010, 5t32mh067763-10, R21TR003103, 5r01mh107419-05, KL2TR000069, UL1TR000067, RR15241, MH099064, HD24061, P41 RR15241, T32MH67763, EB020403, RR-00052, UL1TR001863)
- School of Medicine, New York University
- Intellectual and Developmental Disabilities Research Center (HD-24061)
- University of California, Irvine
- College of Medicine, Seoul National University
- Laureate Institute for Brain Research, University of Tulsa
- Canadian Institutes of Health Research (U01MH099059)
- Medical Research Council (FP7/20072013, EU FP7)
- National Health and Medical Research Council (384419, 384419 and 569533, 1065895, 569533, 1008522)
- Japan Society for the Promotion of Science (18K15523)
- Agència de Gestió d'Ajuts Universitaris i de Recerca (2017SGR, 2017 SGR 881)
- Universitat Politècnica de València
- Instituto de Salud Carlos III (PI16/, CPII16/00048, PI12/01139, PI13/01958, PI11/, PI14/, PI16/00950, 728018, PI040829, FI17/00294, PI16/00889, FP7/2007-2013, Marató de TV3, PI14/00419, 00048)
- European Regional Development Fund (CPII16/00048, 667302, FP7/2007‐2013, FI17/00294, 2007 – 2013, PI13/01958, PI16/00889, 728018, PI16/00950)
- National Institute of Mental Health (R01 MH 62873, R01MH111794, K23MH087770, R01-MH099064, R21MH101441, K23MH092397, R01MH085900, K99MH091238, R01MH115357, MH115357, R01MH094639, R21MH093889, R01MH081803, R01MH081864, K23-MH104515, R01 MH86654, K23MH115206, R01MH083246, R01MH085328, R01MH062873, R00MH091238, R33MH107589, M01 RR00052, R01MH078160, T32MH-067763, U01MH099059, R01MH086654, K23MH082176, R61MH121640, MH099064, L40 MH098392, T32MH073517, R01-MH107419)
- National Institute on Drug Abuse (HHSN271200800009C, U01DA041148)
- National Institute of Neurological Disorders and Stroke (R01NS048527)
- National Institute of Biomedical Imaging and Bioengineering (U54EB020403)
- National Center for Research Resources (P41RR015241, M01RR000052)
- National Center for Advancing Translational Sciences (UL1TR000067/KL2TR00069)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (P30HD024061)
- Cilag
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Attention Deficit Hyperactivity Disorder
- Life Sciences › Neuroscience › Cognitive Neuroscience › Autism Spectrum Disorder Research
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
- Keywords
- attention deficit hyperactivity disorder, autism spectrum disorder, obsessive-compulsive disorder, neurodevelopmental disorders, subcortical volume, cortical thickness, cortical surface area, hippocampal volume, intracranial volume, frontal cortex, structural brain differences, mega-analysis, age differences
- MeSH terms
- Autism Spectrum Disorder, Adolescent, Adult, Attention Deficit Disorder with Hyperactivity, Child, Female, Humans, Human Development, Male, Obsessive-Compulsive Disorder, Organ Size, Psychopathology, Systems Analysis, Cerebrum, Research Report, Neuroimaging
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