Brain imaging of the cortex in ADHD: A coordinated analysis of large-scale clinical and population-based samples

Martine Hoogman, Ryan Muetzel, Joao P. Guimaraes, Elena Shumskaya, Maarten Mennes, Marcel P. Zwiers, Neda Jahanshad, Gustavo Sudre, Thomas Wolfers, Eric A. Earl, Juan Carlos Soliva Vila, Yolanda Vives-Gilabert, Sabin Khadka, Stephanie E. Novotny, Catharina A. Hartman, Dirk J. Heslenfeld, Lizanne J.S. Schweren, Sara Ambrosino, Bob Oranje, Patrick De Zeeuw OranjeTiffany M. Chaim-Avancini, Pedro G.P. Rosa, Marcus V. Zanetti, Charles B. Malpas, Gregor Kohls, Georg G. Von Polier, Jochen Seitz, Joseph Biederman, Alysa E. Doyle, Anders M. Dale, Theo G.M. van Erp, Jeffery N. Epstein, Terry L. Jernigan, Ramona Baur-Streubel, Georg C. Ziegler, Kathrin C. Zierhut, Anouk Schrantee, Marie F. Høvik, Astri J. Lundervold, Clare Kelly, Hazel McCarthy, Norbert Skokauskas, Ruth L. O'Gorman Tuura, Anna Calvo, Sara Lera-Miguel, Rosa Nicolau, Kaylita C. Chantiluke, Anastasia Christakou, Alasdair Vance, Mara Cercignani, Matt C. Gabel, Philip Asherson, Sarah Baumeister, Daniel Brandeis, Sarah Hohmann, Ivanei E. Bramati, Fernanda Tovar-Moll, Andreas J. Fallgatter, Bernd Kardatzki, Lena Schwarz, Anatoly Anikin, Alexandr Baranov, Tinatin Gogberashvili, Dmitry Kapilushniy, Anastasia Solovieva, Hanan El Marroun, Tonya White, Georgii Karkashadze, Leyla Namazova-Baranova, Thomas Ethofer, Paulo Mattos, Tobias Banaschewski, David Coghill, Kerstin J. Plessen, Jonna Kuntsi, Mitul A. Mehta, Yannis Paloyelis, Neil A. Harrison, Mark A. Bellgrove, Tim J. Silk, Ana I. Cubillo, Katya Rubia, Luisa Lazaro, Silvia Brem, Susanne Walitza, Thomas Frodl, Mariam Zentis, Francisco X. Castellanos, Yuliya N. Yoncheva, Jan Haavik, Liesbeth Reneman, Annette Conzelmann, Klaus Peter Lesch, Paul Pauli, Andreas Reif, Leanne Tamm, Kerstin Konrad, Eileen Oberwelland Weiss, Geraldo F. Busatto, Mario R. Louza, Sarah Durston, Pieter J. Hoekstra, Jaap Oosterlaan, Michael C. Stevens, J. Antoni Ramos-Quiroga, Oscar Vilarroya, Damien A. Fair, Joel T. Nigg, Paul M. Thompson, Jan K. Buitelaar, Stephen V. Faraone, Philip Shaw, Henning Tiemeier, Janita Bralten, Barbara Franke

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200 Citations (Scopus)


Objective: Neuroimaging studies show structural alterations of various brain regions in children and adults with attention deficit hyperactivity disorder (ADHD), although nonrepli-cations are frequent. The authors sought to identify cortical characteristics related to ADHD using large-scale studies. Methods: Cortical thickness and surface area (based on the Desikan–Killiany atlas) were compared between case subjects with ADHD (N=2,246) and control subjects (N=1,934) for children, adolescents, and adults separately in ENIGMA-ADHD, a consortium of 36 centers. To assess familial effects on cortical measures, case subjects, unaffected siblings, and control subjects in the NeuroIMAGE study (N=506) were compared. Associations of the attention scale from the Child Behavior Checklist with cortical measures were determined in a pediatric population sample (Generation-R, N=2,707). Results: In the ENIGMA-ADHD sample, lower surface area values were found in children with ADHD, mainly in frontal, cingulate, and temporal regions; the largest significant effect was for total surface area (Cohen’s d=20.21). Fusiform gyrus and temporal pole cortical thickness was also lower in children with ADHD. Neither surface area nor thickness differences were found in the adolescent or adult groups. Familial effects were seen for surface area in several regions. In an overlapping set of regions, surface area, but not thickness, was associated with attention problems in the Generation-R sample. Conclusions: Subtle differences in cortical surface area are widespread in children but not adolescents and adults with ADHD, confirming involvement of the frontal cortex and highlighting regions deserving further attention. Notably, the alterations behave like endophenotypes in families and are linked to ADHD symptoms in the population, extending evidence that ADHD behaves as a continuous trait in the population. Future longitudinal studies should clarify individual lifespan trajectories that lead to nonsignificant findings in adolescent and adult groups despite the presence of an ADHD diagnosis.

Original languageEnglish
Pages (from-to)531-542
Number of pages12
JournalAmerican Journal of Psychiatry
Issue number7
Publication statusPublished - Jul 2019

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