Analysis of structural brain asymmetries in attention-deficit/hyperactivity disorder in 39 datasets

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

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Objective: Some 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.

Methods: We 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.

Results: There 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.

Conclusion: Prior 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.

Original languageEnglish
Pages (from-to)1202-1219
Number of pages18
JournalJournal of Child Psychology and Psychiatry
Issue number10
Early online date22 Mar 2021
Publication statusPublished - Oct 2021


  • Attention-deficit
  • brain asymmetry
  • brain laterality
  • hyperactivity disorder
  • large-scale data
  • structural MRI

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Developmental and Educational Psychology
  • Psychiatry and Mental health


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