Merel C Postema1, Martine Hoogman2,3, Sara Ambrosino4, Philip Asherson5, Tobias Banaschewski6, Cibele E Bandeira7,8, Alexandr Baranov9, Claiton H D Bau7,8,10, Sarah Baumeister6, Ramona Baur-Streubel11, Mark A Bellgrove12, Joseph Biederman13,14, Janita Bralten2,3, Daniel Brandeis15,16, Silvia Brem16,15, Jan K Buitelaar17,18, Geraldo F Busatto19, Francisco X Castellanos20,21, Mara Cercignani22, Tiffany M Chaim-Avancini19, Kaylita C Chantiluke23, Anastasia Christakou23,24, David Coghill25,26, Annette Conzelmann27,28, Ana I Cubillo23, Renata B Cupertino7,8, Patrick de Zeeuw29, Alysa E Doyle14,30, Sarah Durston29, Eric A Earl31, Jeffery N Epstein32,33, Thomas Ethofer34, Damien A Fair31, Andreas J Fallgatter35,36, Stephen V Faraone37, Thomas Frodl38,39, Matt C Gabel22, Tinatin Gogberashvili40, Eugenio H Grevet7,8,10, Jan Haavik41,42, Neil A Harrison22,43, Catharina A Hartman44, Dirk J Heslenfeld45, Pieter J Hoekstra46, Sarah Hohmann6, Marie F Høvik42,47, Terry L Jernigan48, Bernd Kardatzki49, Georgii Karkashadze9, Clare Kelly50,51, Gregor Kohls52, Kerstin Konrad52,53, Jonna Kuntsi5, Luisa Lazaro54,55, Sara Lera-Miguel56, Klaus-Peter Lesch57,58,59, Mario R Louza60, Astri J Lundervold41,61, Charles B Malpas62,63, Paulo Mattos64,65, Hazel McCarthy39,66, Leyla Namazova-Baranova9,67, Rosa Nicolau68, Joel T Nigg31,69, Stephanie E Novotny70, Eileen Oberwelland Weiss71,72, Ruth L O'Gorman Tuura73,74, Jaap Oosterlaan75,76, Bob Oranje29, Yannis Paloyelis77, Paul Pauli78, Felipe A Picon7, Kerstin J Plessen79,80, J Antoni Ramos-Quiroga81,82,83,84, Andreas Reif85, Liesbeth Reneman86, Pedro G P Rosa19, Katya Rubia23, Anouk Schrantee87, Lizanne J S Schweren44, Jochen Seitz88, Philip Shaw89, Tim J Silk90,91, Norbert Skokauskas92,93, Juan C Soliva Vila94, Michael C Stevens70,95, Gustavo Sudre96, Leanne Tamm97,98, Fernanda Tovar-Moll64,99, Theo G M van Erp100,101, Alasdair Vance102, Oscar Vilarroya94,103, Yolanda Vives-Gilabert104, Georg G von Polier88,105, Susanne Walitza15, Yuliya N Yoncheva106, Marcus V Zanetti107,108, Georg C Ziegler57, David C Glahn70,109, Neda Jahanshad110, Sarah E Medland111, Paul M Thompson112, Simon E Fisher1,3, Barbara Franke2,3,113, Clyde Francks1,3. 1. Language and Genetics Department, Max Planck Institute for Psycholinguistics, Nijmegen, The Netherlands. 2. Department of Human Genetics, Radboud University Medical Center, Nijmegen, Netherlands. 3. Donders Institute for Brain, Cognition and Behaviour, Radboud University, Nijmegen, Netherlands. 4. NICHE lab, Department of Psychiatry, University Medical Center Utrecht Brain Center, Utrecht University, Utrecht, The Netherlands. 5. Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK. 6. Department of Child and Adolescent Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim/Heidelberg University, Mannheim, Germany. 7. Adulthood ADHD Outpatient Program (ProDAH), Clinical Research Center, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil. 8. Department of Genetics, Institute of Biosciences, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil. 9. Research Institute of Pediatrics and Child Health of Central Clinical Hospital of the Russian Academy of Sciences of the Ministry of Science and Higher Education of the Russian Federation, Moscow, Russia. 10. Developmental Psychiatry Program, Experimental Research Center, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil. 11. Department of Biological Psychology, Clinical Psychology and Psychotherapy, University of Würzburg, Würzburg, Germany. 12. Turner Institute for Brain and Mental Health and School of Psychological Sciences, Monash University, Melbourne, Vic., Australia. 13. Clinical and Research Programs in Pediatric Psychopharmacology and Adult ADHD, Boston, MA, USA. 14. Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA. 15. Department of Child and Adolescent Psychiatry and Psychotherapy, Psychiatric Hospital, University of Zurich, Zurich, Switzerland. 16. The Neuroscience Center Zurich, University of Zurich and ETH Zurich, Zurich, Switzerland. 17. Department of Cognitive Neuroscience, Donders Institute for Brain, Cognition and Behaviour, Radboudumc, Nijmegen, The Netherlands. 18. Karakter Child and Adolescent Psychiatry University Center, Nijmegen, The Netherlands. 19. Laboratory of Psychiatric Neuroimaging (LIM-21, Department and Institute of Psychiatry, Hospital das Clinicas HCFMUSP, Faculty of Medicine, University of São Paulo, Sao Paulo, Sao Paulo, Brazil. 20. Department of Child and Adolescent Psychiatry, NYU Grossman School of Medicine, New York, NY, USA. 21. Nathan Kline Institute for Psychiatric Research, Orangeburg, NY, USA. 22. Department of Neuroscience, Brighton and Sussex Medical School, Falmer, Brighton, UK. 23. Department of Child and Adolescent Psychiatry, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK. 24. School of Psychology and Clinical Language Sciences, Centre for Integrative Neuroscience and Neurodynamics, University of Reading, Reading, UK. 25. Departments of Paediatrics and Psychiatry, University of Melbourne, Melbourne, Vic., Australia. 26. Murdoch Children's Research Institute, Melbourne, Vic., Australia. 27. Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, University Hospital of Tübingen, Tübingen, Germany. 28. Department of Psychology (Clinical Psychology II), PFH - Private University of Applied Sciences, Göttingen, Germany. 29. NICHE Lab, Department of Psychiatry, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, The Netherlands. 30. Center for Genomic Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA. 31. Department of Behavioral Neuroscience, Oregon Health & Science University, Portland, OR, USA. 32. Division of Behavioral Medicine and Clinical Psychology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA. 33. Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA. 34. Clinic for Psychiatry/Psychotherapy Tübingen/Department for Biomedical Magnetic Resonance, Tübingen, Germany. 35. Department of Psychiatry and Psychotherapy, University Hospital of Tuebingen, Tuebingen, Germany. 36. LEAD Graduate School, University of Tuebingen, Tübingen, Germany. 37. Departments of Psychiatry and of Neuroscience and Physiology, SUNY Upstate Medical University, Syracuse, NY, USA. 38. Department of Psychiatry and Psychotherapy, Otto von Guericke University, Magdeburg, Germany. 39. Department of Psychiatry, Trinity College Dublin, Dublin, Ireland. 40. Laboratory of Neurology and Cognitive Health, National Medical Research Center for Children's Health, Moscow, Russia. 41. Department of Biomedicine, K.G. Jebsen Centre for Neuropsychiatric Disorders, University of Bergen, Bergen, Norway. 42. Division of Psychiatry, Haukeland University Hospital, Bergen, Norway. 43. Sussex Partnership NHS Foundation Trust, Swandean, East Sussex, UK. 44. Department of Psychiatry, Interdisciplinary Center Psychopathology and Emotion Regulation (ICPE), University Medical Center Groningen, University of Groningen, Groningen, The Netherlands. 45. Faculty of Behavioural and Movement Sciences, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands. 46. Department of Child and Adolescent Psychiatry, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands. 47. Department of Clinical Medicine, University of Bergen, Bergen, Norway. 48. Center for Human Development, UC San Diego, La Jolla, CA, USA. 49. Department of Biomedical Magnetic Resonance, University of Tuebingen, Tuebingen, Germany. 50. School of Psychology and Department of Psychiatry at the School of Medicine, Trinity College Dublin, Ireland. 51. Trinity College Institute of Neuroscience, Trinity College Dublin, Dublin, Ireland. 52. Child Neuropsychology Section, Department of Child and Adolescent Psychiatry, Psychosomatics, and Psychotherapy, University Hospital RWTH, Aachen, Germany. 53. JARA Institute Molecular Neuroscience and Neuroimaging (INM-11), Institute for Neuroscience and Medicine, Research Center Jülich, Jülich, Germany. 54. Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Biomedical Network Research Center on Mental Health (CIBERSAM), Barcelona, Spain. 55. Department of Medicine, University of Barcelona, Barcelona, Spain. 56. Department of Child and Adolescent Psychiatry and Psychology, Institute of Neurosciencies, Hospital Clinic, Barcelona, Spain. 57. Division of Molecular Psychiatry, Center of Mental Health, University of Würzburg, Würzburg, Germany. 58. Laboratory of Psychiatric Neurobiology, Institute of Molecular Medicine, I.M. Sechenov First Moscow State Medical University, Moscow, Russia. 59. Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience (MHeNS), Maastricht University, Maastricht, The Netherlands. 60. Institute of Psychiatry, Faculty of Medicine, University of São Paulo, São Paulo, Brazil. 61. Department of Biological and Medical Psychology, University of Bergen, Bergen, Norway. 62. Developmental Imaging Group, Murdoch Children's Research Institute, Melbourne, Vic., Australia. 63. Clinical Outcomes Research Unit (CORe), Department of Medicine, Royal Melbourne Hospital, The University of Melbourne, Melbourne, Vic., Australia. 64. D'Or Institute for Research and Education, Rio de Janeiro, Brazil. 65. Federal University of Rio de Janeiro, Rio de Janeiro, Brazil. 66. Centre of Advanced Medical Imaging, St James's Hospital, Dublin, Ireland. 67. Russian National Research Medical University Ministry of Health of the Russian Federation, Moscow, Russia. 68. Department of Child and Adolescent Psychiatry and Psychology, Institut of Neurosciencies, Hospital Clinic, Barcelona, Spain. 69. Department of Psychiatry, Oregon Health & Science University, Portland, OR, USA. 70. Olin Neuropsychiatry Research Center, Hartford Hospital, Hartford, CT, USA. 71. Translational Neuroscience, Child and Adolescent Psychiatry, University Hospital RWTH Aachen, Aachen, Germany. 72. Cognitive Neuroscience (INM-3), Institute for Neuroscience and Medicine, Research Center Jülich, Jülich, Germany. 73. Center for MR Research, University Children's Hospital, Zurich, Switzerland. 74. Zurich Center for Integrative Human Physiology (ZIHP), Zurich, Switzerland. 75. Clinical Neuropsychology Section, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands. 76. Emma Neuroscience Group, Department of Pediatrics, Amsterdam Reproduction & Development, Emma Children's Hospital Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, The Netherlands. 77. Department of Neuroimaging, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK. 78. Department of Psychology (Biological Psychology, Clinical Psychology and Psychotherapy) and Center of Mental Health, University of Würzburg, Würzburg, Germany. 79. Child and Adolescent Mental Health Centre, Capital Region Copenhagen, Copenhagen, Denmark. 80. Division of Child and Adolescent Psychiatry, Department of Psychiatry, University Hospital Lausanne, Lausanne, Switzerland. 81. Department of Psychiatry, Hospital Universitari Vall d'Hebron, Barcelona, Catalonia, Spain. 82. Group of Psychiatry, Mental Health and Addictions, Vall d'Hebron Research Institute (VHIR), Barcelona, Catalonia, Spain. 83. Biomedical Network Research Centre on Mental Health (CIBERSAM), Barcelona, Catalonia, Spain. 84. Department of Psychiatry and Legal Medicine, Universitat Autònoma de Barcelona, Barcelona, Catalonia, Spain. 85. Department of Psychiatry, Psychosomatic Medicine and Psychotherapy, University Hospital Frankfurt, Frankfurt, Germany. 86. Academic Medical Center, Amsterdam University Medical Center, Amsterdam, The Netherlands. 87. Department of Radiology and Nuclear Medicine, Amsterdam University Medical Centers, Amsterdam, The Netherlands. 88. Child and Adolescent Psychiatry, University Hospital RWTH Aachen, Aachen, Germany. 89. National Human Genome Research Institute and National Institute of Mental health, Bethesda, MD, USA. 90. School of Psychology, Deakin University, Geelong, Vic., Australia. 91. Murdoch Children's Research Institute, Developmental Imaging, Melbourne, Vic., Australia. 92. Centre for Child and Adolescent Mental Health, NTNU, Trondheim, Norway. 93. Institute of Mental Health, Norwegian University of Science and Technology, Trondheim, Norway. 94. Department of Psychiatry and Forensic Medicine, Universitat Autonoma de Barcelona, Barcelona, Spain. 95. Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA. 96. National Human Genome Research Institute, Bethesda, MD, USA. 97. Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA. 98. College of Medicine, University of Cincinnati, Cincinnati, OH, USA. 99. Morphological Sciences Program, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil. 100. Clinical Translational Neuroscience Laboratory, Department of Psychiatry and Human Behavior, University of California Irvine, Irvine, CA, USA. 101. Center for the Neurobiology of Learning and Memory, University of California Irvine, Irvine, CA, USA. 102. Department of Paediatrics, University of Melbourne, Parkville, Vic., Australia. 103. Hospital del Mar Medical Research Institute (IMIM), Barcelona, Spain. 104. Instituto ITACA, Universitat Politècnica de València, València, Spain. 105. Brain and Behavior (INM-7), Institute for Neuroscience and Medicine, Research Center Jülich, Jülich, Germany. 106. Department of Child and Adolescent Psychiatry, NYU Child Study Center, Hassenfeld Children's Hospital at NYU Langone, New York, NY, USA. 107. Department of Psychiatry, Faculty of Medicine, University of São Paulo, São Paulo, Brazil. 108. Hospital Sírio-Libanês, São Paulo, Brazil. 109. Department of Psychiatry, Boston Children's Hospital and Harvard Medical School, Boston, MA, USA. 110. Imaging Genetics Center, Stevens Neuroimaging and Informatics Institute, Keck School of Medicine of USC, Los Angeles, CA, USA. 111. Psychiatric Genetics, QIMR Berghofer Medical Research Institute, Brisbane, Qld, Australia. 112. Imaging Genetics Center, Stevens Institute for Neuroimaging & Informatics, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA. 113. Department of Psychiatry, Radboud University Medical Center, Nijmegen, The Netherlands.
Abstract
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.
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.
Authors: Tulio Guadalupe; Marcel P Zwiers; Alexander Teumer; Katharina Wittfeld; Alejandro Arias Vasquez; Martine Hoogman; Peter Hagoort; Guillen Fernandez; Jan Buitelaar; Katrin Hegenscheid; Henry Völzke; Barbara Franke; Simon E Fisher; Hans J Grabe; Clyde Francks Journal: Hum Brain Mapp Date: 2013-11-04 Impact factor: 5.038
Authors: F X Castellanos; J N Giedd; W L Marsh; S D Hamburger; A C Vaituzis; D P Dickstein; S E Sarfatti; Y C Vauss; J W Snell; N Lange; D Kaysen; A L Krain; G F Ritchie; J C Rajapakse; J L Rapoport Journal: Arch Gen Psychiatry Date: 1996-07
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Authors: Peristera Paschou; Yin Jin; Kirsten Müller-Vahl; Harald E Möller; Renata Rizzo; Pieter J Hoekstra; Veit Roessner; Nanette Mol Debes; Yulia Worbe; Andreas Hartmann; Pablo Mir; Danielle Cath; Irene Neuner; Heike Eichele; Chencheng Zhang; Katarzyna Lewandowska; Alexander Munchau; Julius Verrel; Richard Musil; Tim J Silk; Colleen A Hanlon; Emily D Bihun; Valerie Brandt; Andrea Dietrich; Natalie Forde; Christos Ganos; Deanna J Greene; Chunguang Chu; Michel J Grothe; Tamara Hershey; Piotr Janik; Jonathan M Koller; Juan Francisco Martin-Rodriguez; Karsten Müller; Stefano Palmucci; Adriana Prato; Shukti Ramkiran; Federica Saia; Natalia Szejko; Renzo Torrecuso; Zeynep Tumer; Anne Uhlmann; Tanja Veselinovic; Tomasz Wolańczyk; Jade-Jocelyne Zouki; Pritesh Jain; Apostolia Topaloudi; Mary Kaka; Zhiyu Yang; Petros Drineas; Sophia I Thomopoulos; Tonya White; Dick J Veltman; Lianne Schmaal; Dan J Stein; Jan Buitelaar; Barbara Franke; Odile van den Heuvel; Neda Jahanshad; Paul M Thompson; Kevin J Black Journal: Front Psychiatry Date: 2022-08-18 Impact factor: 5.435
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Authors: Zhiqiang Sha; Dick Schijven; Amaia Carrion-Castillo; Marc Joliot; Bernard Mazoyer; Simon E Fisher; Fabrice Crivello; Clyde Francks Journal: Nat Hum Behav Date: 2021-03-15