Analysis of structural brain asymmetries in attention‐deficit/hyperactivity disorder in 39 datasets
Authors: Postema Merel C. , Hoogman Martine , Ambrosino Sara , Asherson Philip , Banaschewski Tobias , Bandeira Cibele E. , Baranov Alexandr , Bau Claiton H.D. , Baumeister Sarah , Baur‐Streubel Ramona , Bellgrove Mark A. , Biederman Joseph , Bralten Janita , Brandeis Daniel , Brem Silvia , Buitelaar Jan K. , Busatto Geraldo F. , Castellanos Francisco X. , Cercignani Mara , Chaim‐Avancini Tiffany M. , Chantiluke Kaylita C. , Christakou Anastasia , Coghill David , Conzelmann Annette , Cubillo Ana I. , Cupertino Renata B. , de Zeeuw Patrick , Doyle Alysa E. , Durston Sarah , Earl Eric A. , Epstein Jeffery N. , Ethofer Thomas , Fair Damien A. , Fallgatter Andreas J. , Faraone Stephen V. , Frodl Thomas , Gabel Matt C. , Gogberashvili Tinatin , Grevet Eugenio H. , Haavik Jan , Harrison Neil A. , Hartman Catharina A. , Heslenfeld Dirk J. , Hoekstra Pieter J. , Hohmann Sarah , Høvik Marie F. , Jernigan Terry L. , Kardatzki Bernd , Karkashadze Georgii , Kelly Clare , Kohls Gregor , Konrad Kerstin , Kuntsi Jonna , Lazaro Luisa , Lera‐Miguel Sara , Lesch Klaus‐Peter , Louza Mario R. , Lundervold Astri J. , Malpas Charles B , Mattos Paulo , McCarthy Hazel , Namazova‐Baranova Leyla , Nicolau Rosa , Nigg Joel T. , Novotny Stephanie E. , Oberwelland Weiss Eileen , O'Gorman Tuura Ruth L. , Oosterlaan Jaap , Oranje Bob , Paloyelis Yannis , Pauli Paul , Picon Felipe A. , Plessen Kerstin J. , Ramos‐Quiroga J. Antoni , Reif Andreas , Reneman Liesbeth , Rosa Pedro G.P. , Rubia Katya , Schrantee Anouk , Schweren Lizanne J.S. , Seitz Jochen , Shaw Philip , Silk Tim J. , Skokauskas Norbert , Soliva Vila Juan C. , Stevens Michael C. , Sudre Gustavo , Tamm Leanne , Tovar‐Moll Fernanda , van Erp Theo G.M. , Vance Alasdair , Vilarroya Oscar , Vives‐Gilabert Yolanda , von Polier Georg G. , Walitza Susanne , Yoncheva Yuliya N. , Zanetti Marcus V. , Ziegler Georg C. , Glahn David C. , Jahanshad Neda , Medland Sarah E. ,   ENIGMA ADHD Working Group, Thompson Paul M. , Fisher Simon E. , Franke Barbara , Francks Clyde 
Published: March 2021

ObjectiveSome studies have suggested alterations of structural brain asymmetry in attention‐deficit/hyperactivity disorder (ADHD), but findings have been contradictory and based on small samples. Here, we performed the largest ever analysis of brain left‐right asymmetry in ADHD, using 39 datasets of the ENIGMA consortium.MethodsWe analyzed asymmetry of subcortical and cerebral cortical structures in up to 1,933 people with ADHD and 1,829 unaffected controls. Asymmetry Indexes (AIs) were calculated per participant for each bilaterally paired measure, and linear mixed effects modeling was applied separately in children, adolescents, adults, and the total sample, to test exhaustively for potential associations of ADHD with structural brain asymmetries.ResultsThere was no evidence for altered caudate nucleus asymmetry in ADHD, in contrast to prior literature. In children, there was less rightward asymmetry of the total hemispheric surface area compared to controls (t = 2.1, p = .04). Lower rightward asymmetry of medial orbitofrontal cortex surface area in ADHD (t = 2.7, p = .01) was similar to a recent finding for autism spectrum disorder. There were also some differences in cortical thickness asymmetry across age groups. In adults with ADHD, globus pallidus asymmetry was altered compared to those without ADHD. However, all effects were small (Cohen’s d from −0.18 to 0.18) and would not survive study‐wide correction for multiple testing.ConclusionPrior studies of altered structural brain asymmetry in ADHD were likely underpowered to detect the small effects reported here. Altered structural asymmetry is unlikely to provide a useful biomarker for ADHD, but may provide neurobiological insights into the trait.