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Subcortical brain volume, regional cortical thickness and cortical surface area across attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD), and obsessive-compulsive disorder (OCD): findings from the ENIGMA-ADHD, -ASD, and -OCD working groups

By Premika SW Boedhoe, Daan van Rooij, Martine Hoogman, Jos W.R. Twisk, Lianne Schmaal, Yoshinari Abe, Pino Alonso, Stephanie H Ameis, Anatoly Anikin, Alan Anticevic, Philip Aherson, Celso Arango, Paul D Arnold, Francesca Assogna, Guillaume Auzias, Tobias Banaschewski, Alexander Baranov, Marcelo C. Batistuzzo, Sarah Baumeister, Ramona Baur-Streubel, Marlene Behrmann, Mark A Bellgrove, Francesco Benedetti, Jan C. Beucke, Joseph Biederman, Irene Bollettini, Anushree Bose, Janita Bralten, Ivanei E. Bramati, Daniel Brandeis, Silvia Brem, Brian P. Brennan, Geraldo F. Busatto, Sara Calderoni, Anna Calvo, Rosa Calvo, Francisco X. Castellanos, Mara Cercignani, Tiffany M. Chaim-Avancini, Kaylita C. Chantiluke, Yuqi Cheng, Kang Ik K. Cho, Anastasia Christakou, David Coghill, Annette Conzelmann, Ana I. Cubillo, Anders M Dale, Sara Dallaspezia, Eileen Daly, Damiaan Denys, Christine Deruelle, Adriana Di Martino, Ilan Dinstein, Alysa E. Doyle, Sarah Durston, Eric A. Earl, Christine Ecker, Stefan Ehrlich, Benjamin A. Ely, Jeffery N. Epstein, Thomas Ethofer, Damien A. Fair, Andreas J. Fallgatter, Stephen V. Faraone, Jennifer Fedor, Xin Feng, Jamie D. Feusner, Jackie Fitzgerald, Kate D. Fitzgerald, Jean-Paul Fouche, Christine M. Freitag, Egill A. Fridgeirsson, Thomas Frodl, Matt C. Gabel, Louise Gallagher, Tinatin Gogberashvili, Ilaria Gori, Patricia Gruner, Deniz A. Gürsel, Shlomi Haar, Jan Haavik, Geoffrey B. Hall, Neil A. Harrison, Catharina A. Hartman, Dirk J. Heslenfeld, Yoshiyuki Hirano, Pieter J. Hoekstra, Marcelo Q. Hoexter, Sarah Hohmann, Marie F. Høvik, Hao Hu, Chaim Huyser, Neda Jahanshad, Maria Jalbrzikowski, Anthony James, Joost Janssen, Fern Jaspers-Fayer, Terry L Jernigan, Dmitry Kapilushniy, Bernd Kardatzki, Georgii Karkashadze, Norbert Kathmann, Christian Kaufmann, Clare Kelly, Sabin Khadka, Joseph A. King, Kathrin Koch, Gregor Kohls, Kerstin Kohls, Masaru Kuno, Jonna Kuntsi, Gerd Kvale, Jun Soo Kwon, Luisa Lázaro, Sara Lera-Miguel, Klaus-Peter Lesch, Liesbeth Hoekstra, Yanni Liu, Christine Lochner, Mario R. Louza, Beatriz Luna, Astri J. Lundervold, Charles B Malpas, Paulo Marques, Rachel Marsh, Ignacio Martínez-Zalacaín, David Mataix-Cols, Paulo Mattos, Hazel McCarthy, Jane McGrath, Mitul A Mehta, José M Menchón, Maarten Mennes, Mauricio Moller Martinho, Pedro S Moreira, Astrid Morer, Pedro Morgado, Filippo Muratori, Clodagh M. Murphy, Declan G.M. Murphy, Akiko Nakagawa, Takashi Nakamae, Tomohiro Nakao, Leyla Namazova-Baranova, Janardhanan C. Narayanaswamy, Rosa Nicolau, Joel T. Nigg, Stephanie E. Novotny, Erika L. Nurmi, Eileen Oberwelland Weiss, Ruth L. O’Gorman Tuura, Kirsten O’Hearn, Joseph O’Neill, Jaap Oosterlaan, Bob Oranje, Yannis Paloyelis, Mara Parellada, Paul Pauli, Chris Perriello, John Piacentini, Fabrizio Piras, Federica Piras, Kerstin J. Plessen, Olga Puig, J. Antoni Ramos-Quiroga, Y.C. Janardhan Reddy, Andreas Reif, Liesbeth Reneman, Alessandra Retico, Pedro G.P. Rosa, Katya Rubia, Oana Georgiana Rus, Yuki Sakai, Anouk Schrantee, Lena Schwarz, Lizanne J.S. Schweren, Jochen Seitz, Philip Shaw, Devon Shook, Tim J. Silk, H. Blair Simpson, Norbert Skokauskas, Juan Carlos Soliva Vila, Anastasia Solovieva, Noam Soreni, Carles Soriano-Mas, Gianfranco Spalletta, Emily R. Stern, Michael C. Stevens, S. Evelyn Stewart, Gustavo Sudre, Philip R. Szeszko, Leanne Tamm, Margot J. Taylor, David F. Tolin, Michela Tosetti, Fernanda Tovar-Moll, Aki Tsuchiyagaito, Theo G.M. van Erp, Guido A. van Wingen, Alasdair Vance, Ganesan Venkatasubramanian, Oscar Vilarroya, Yolanda Vives-Gilabert, Georg G. von Polier, Susanne Walitza, Gregory L. Wallace, Zhen Wang, Thomas Wolfers, Yuliya N. Yoncheva, Je-Yeon Yun, Marcus V. Zanetti, Fengfeng Zhou, Georg C. Ziegler, Kathrin C. Zierhut, Marcel P. Zwiers, the ENIGMA-ADHD working group, the ENIGMA-ASD working group, the ENIGMA-OCD working group, Paul M Thompson, Dan J. Stein, Jan Buitelaar, Barbara Franke, Odile A van den Heuvel

Posted 18 Jun 2019
bioRxiv DOI: 10.1101/673012

Objective: Attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD), and obsessive-compulsive disorder (OCD) are common neurodevelopmental disorders that frequently co-occur. We aimed to directly compare all three disorders. The ENIGMA consortium is ideally positioned to investigate structural brain alterations across these disorders. Methods: Structural T1-weighted whole-brain MRI of controls (n=5,827) and 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. We examined subcortical volume, cortical thickness and 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 ICV for subcortical and surface area measures). Results: We found no shared alterations among all three disorders, while shared alterations between any two disorders did not survive multiple comparisons correction. Children with ADHD compared to those with OCD had smaller hippocampal volumes, possibly influenced by IQ. Children and adolescents with ADHD also had smaller ICV than controls and those with OCD or ASD. Adults with ASD showed thicker frontal cortices compared to adult controls and other clinical groups. No OCD-specific alterations across different age-groups and surface area alterations among all disorders in childhood and adulthood were observed. Conclusion: Our findings suggest robust but subtle alterations across different age-groups among ADHD, ASD, and OCD. ADHD-specific ICV and hippocampal alterations in children and adolescents, and ASD-specific cortical thickness alterations in the frontal cortex in adults support previous work emphasizing neurodevelopmental alterations in these disorders.

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