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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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“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
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Metadata
- 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
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- PubMed (publishedVersion)
- Research Publications (Maastricht University) (publishedVersion, other-oa)
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- CentAUR (University of Reading) (acceptedVersion)
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- 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)
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- Figshare (submittedVersion)
- IRIS (submittedVersion)
- Archivio Istituzionale della Ricerca - Università Vita-Salute San Raffaele (submittedVersion)
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- 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)
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- University of Melbourne
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- ZonMw (60-60600-97-193, 917.15.318, 056-13-015, 60600, 433-09-242)
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- 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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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