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

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Document Type: Report; Author abstract
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Keywords: Attention-deficit; hyperactivity disorder; brain asymmetry; brain laterality; structural MRI; large-scale data 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. Article Note: Conflict of interest statement: See Acknowledgements for full disclosures. CAPTION(S): Supplementary Methods Table S1. Characteristics of the different datasets. Table S2. Full linear model results for the subcortical volume AIs in children. Table S3. Full linear model results for the cortical surface area AIs in children. Table S4. Full linear model results for the cortical thickness AIs in children. Table S5. Full linear model results for the subcortical volume AIs in adolescents. Table S6. Full linear model results for the cortical surface area AIs in adolescents. Table S7. Full linear model results for the cortical thickness AIs in adolescents. Table S8. Full linear model results for the subcortical volume AIs in adults. Table S9. Full linear model results for the cortical surface area AIs in adults. Table S10. Full linear model results for the cortical thickness AIs in adults. Table S11. Full linear model results for the subcortical volume AIs in all age groups combined. Table S12. Full linear model results for the cortical surface area AI in all age groups combined. Table S13. Full linear model results for the cortical thickness AIs in all age groups combined. Table S14. Directions of asymmetry changes in ADHD individuals versus controls for those AIs that had shown nominally significant (p Table S15. Sensitivity analyses for the effects of diagnosis in all age groups combined, for subcortical volume AIs. Table S16. Sensitivity analyses for the effects of diagnosis in all age groups combined, for cortical surface area AIs. Table S17. Sensitivity analyses for the effects of diagnosis in all age groups combined, for cortical thickness AIs. Table S18. Associations of subcortical volume AIs with disorder severity in ADHD individuals, all age groups combined. Table S19. Associations of cortical surface area AIs with disorder severity in ADHD individuals, all age groups combined. Table S20. Associations of cortical thickness AIs with disorder severity in ADHD individuals, all age groups combined. Table S21. Associations of subcortical volume AIs with psychostimulant medication use in ADHD individuals, all age groups combined. Table S22. Associations of cortical surface area AIs with psychostimulant medication use in ADHD individuals, all age groups combined. Table S23. Associations of cortical thickness AIs with psychostimulant medication use in ADHD individuals, all age groups combined. Table S24. Associations of subcortical volume AIs with comorbidities in ADHD individuals, all age groups combined. Table S25. Associations of cortical surface area AIs with comorbidities in ADHD individuals, all age groups combined. Table S26. Associations of cortical thickness AIs with comorbidities in ADHD individuals, all age groups combined. Table S27. Associations of subcortical volume AIs with IQ in all age groups combined. Table S28. Associations of cortical surface area AIs with IQ in all age groups combined. Table S29. Associations of cortical thickness AIs with IQ in all age groups combined. Figure S1. Joyplot of the distributions of AIs in the total study sample (without winsorization), in ADHD cases and controls. Figure S2. Correlations between AIs of subcortical volumes in the total study sample, as well as in cases and controls. Figure S3. Correlations between AIs of cortical surface areas in the total study sample, cases, and controls. Figure S4. Correlations between AIs of cortical thickness in the total study sample, cases, and controls. Figure S5. Residual plots of the linear mixed effects model analysis of subcortical volume AIs in the total study sample. Figure S6. Residual plots of the linear mixed effects model analysis of cortical surface area AIs and the AI of the total average surface area (totalsurf) in the total study sample. Figure S7. Residual plots of the linear mixed effects model analysis of cortical thickness AIs and the AI of the total average thickness (totalthick) in the total study sample. Figure S8. Scatter plots of the relationship between age and AIs of the subcortical volumes. Figure S9. Scatter plots of the relationship between age and AIs of the cortical surface areas. Figure S10. Scatter plots of the relationship between age and AIs of the cortical thickness. Figure S11. Distributions of age, sex, handedness, IQ and ICV in ADHD and controls. Figure S12. Distributions within ADHD cases of hyperactivity/impulsivity symptom scores, inattention symptom scores, medication status, and comorbidity status. Figure S13. Bar plots of the Cohen's d effect sizes for diagnosis in the different age groups analyzed. Supplementary References Byline: 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 Cercignani, Tiffany M. Chaim-Avancini, Kaylita C. Chantiluke, Anastasia Christakou, David Coghill, Annette Conzelmann, Ana I. Cubillo, Renata B. Cupertino, Patrick 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 C. Soliva Vila, Michael C. Stevens, Gustavo Sudre, Leanne Tamm, Fernanda Tovar-Moll, Theo G.M. Erp, Alasdair Vance, Oscar Vilarroya, Yolanda Vives-Gilabert, Georg G. 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

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Gale Document Number: GALE|A677151756