. 2024 Aug 1;45(11):e26754.

doi: 10.1002/hbm.26754.

Large-scale analysis of structural brain asymmetries during neurodevelopment: Associations with age and sex in 4265 children and adolescents

F Kurth^{1

2}, D Schijven³, O A van den Heuvel⁴, M Hoogman^{5

6

7}, D van Rooij⁸, D J Stein⁹, J K Buitelaar^{7

10}, S Bölte^{11

12}, G Auzias¹³, A Kushki¹⁴, G Venkatasubramanian^{15

16}, K Rubia¹⁷, S Bollmann¹⁸, J Isaksson^{11

19}, F Jaspers-Fayer²⁰, R Marsh²¹, M C Batistuzzo^{22

23}, P D Arnold²⁴, R A Bressan^{25

26}, S E Stewart²⁷, P Gruner²⁸, L Sorensen²⁹, P M Pan^{30

31}, T J Silk^{32

33}, R C Gur³⁴, A I Cubillo³⁵, J Haavik^{36

37}, R L O'Gorman Tuura³⁸, C A Hartman³⁹, R Calvo^{40

41

42

43}, J McGrath⁴⁴, S Calderoni^{45

46}, A Jackowski^{47

48}, K C Chantiluke¹⁷, T D Satterthwaite^{49

50

51}, G F Busatto⁵², J T Nigg⁵³, R E Gur⁵⁴, A Retico⁵⁵, M Tosetti⁴⁵, L Gallagher^{44

56

57

58}, P R Szeszko^{59

60

61}, J Neufeld^{11

62}, A E Ortiz^{40

43}, C Ghisleni³⁸, L Lazaro^{40

41

42

43}, P J Hoekstra⁶³, E Anagnostou⁶⁴, L Hoekstra^{65

66

67}, B Simpson⁶⁸, J K Plessen⁶⁹, C Deruelle¹³, N Soreni^{70

71}, A James⁷², J Narayanaswamy¹⁵, J Y Reddy¹⁵, J Fitzgerald⁷³, M A Bellgrove⁷⁴, G A Salum^{75

76}, J Janssen⁷⁷, F Muratori⁴⁵, M Vila⁴⁰, M Garcia Giral⁴⁰, S H Ameis^{78

79}, P Bosco⁴⁵, K Lundin Remnélius¹¹, C Huyser^{80

81}, J C Pariente⁸², M Jalbrzikowski^{83

84}, P G Rosa⁸⁵, K M O'Hearn⁸⁶, S Ehrlich⁸⁷, J Mollon⁸⁸, A Zugman⁸⁹, A Christakou^{35

90}, C Arango⁹¹, S E Fisher^{3

7}, X Kong^{92

93}, B Franke^{5

6

7}, S E Medland⁹⁴, S I Thomopoulos⁹⁵, N Jahanshad⁹⁵, D C Glahn^{84

96}, P M Thompson⁹⁵, C Francks^{3

6

7}, E Luders^{1

62

97

98}

Affiliations

¹ School of Psychology, University of Auckland, Auckland, New Zealand.
² Institute of Diagnostic and Interventional Radiology, Jena University Hospital, Jena, Germany.
³ Language and Genetics Department, Max Planck Institute for Psycholinguistics, Nijmegen, The Netherlands.
⁴ Department of Psychiatry, Amsterdam University Medical Center, Amsterdam, The Netherlands.
⁵ Department of Psychiatry, Radboud University Medical Center, Nijmegen, The Netherlands.
⁶ Department of Human Genetics, Radboud University Medical Center, Nijmegen, The Netherlands.
⁷ Donders Institute for Brain, Cognition and Behaviour, Radboud University, Nijmegen, The Netherlands.
⁸ Donders Institute for Brain, Cognition and Behavior, Department of Cognitive Neuroscience, Radboud University Medical Center, Nijmegen, The Netherlands.
⁹ SAMRC Unit on Risk & Resilience in Mental Disorders, Department of Psychiatry & Neuroscience Institute, University of Cape Town, Cape Town, South Africa.
¹⁰ Department of Cognitive Neuroscience, Radboudumc, Nijmegen, The Netherlands.
¹¹ Center of Neurodevelopmental Disorders (KIND), Centre for Psychiatry Research, Department of Women's and Children's Health, Karolinska Institutet & Stockholm Health Care Services, Region Stockholm, Stockholm, Sweden.
¹² Curtin Autism Research Group, Curtin School of Allied Health, Curtin University, Perth, Australia.
¹³ Institut de neurosciences de la Timone UMR 7289, Aix-Marseille Université & CNRS, Marseille, France.
¹⁴ Holland Bloorview Kids Rehabilitation Hospital, Institute for Biomedical Engineering, University of Toronto, Toronto, Canada.
¹⁵ National Institute of Mental Health and Neuro Sciences (NIMHANS), Bengaluru, India.
¹⁶ Department of Psychiatry, Temerty Faculty of Medicine, University of Toronto, Toronto, Canada.
¹⁷ Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK.
¹⁸ School of Information Technology and Electrical Engineering, The University of Queensland, Brisbane, Australia.
¹⁹ Child and Adolescent Psychiatry Unit, Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
²⁰ BC Children's Research Institute and the University of British Columbia, Vancouver, Canada.
²¹ Department of Psychiatry, Columbia University Irving Medical Center and the New York State Psychiatric Institute, New York, New York, USA.
²² Department & Institute of Psychiatry, University of Sao Paulo, Medical School, Sao Paulo, Brazil.
²³ Department of Methods and Techniques in Psychology, Pontifical Catholic University, Sao Paulo, Brazil.
²⁴ The Mathison Centre for Mental Health Research & Education, Hotchkiss Brain Institute, University of Calgary, Calgary, Canada.
²⁵ Federal University of São Paulo, São Paulo, Brazil.
²⁶ Instituto Ame Sua Mente, São Paulo, Brazil.
²⁷ British Columbia Children's Hospital, British Columbia Mental Health and Substance Use Services, University of British Columbia, Vancouver, Canada.
²⁸ Department of Psychiatry, Yale University, New Haven, Connecticut, USA.
²⁹ Department of Biological and Medical Psychology, University of Bergen, Bergen, Norway.
³⁰ Laboratório de Neurociências Integrativas (LINC), Departamento de Psiquiatria, Universidade Federal de São Paulo (UNIFESP), São Paulo, Brazil.
³¹ Instituto Nacional de siquiatria do Desenvolvimento (INPD), São Paulo, Brazil.
³² Centre for Social and Early Emotional Development and School of Psychology, Deakin University, Geelong, Australia.
³³ Murdoch Children's Research Institute, Melbourne, Australia.
³⁴ Department of Psychiatry, Section on Neurodevelopment and Psychosis and the Lifespan Brain Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
³⁵ Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
³⁶ Department of Biomedicine, University of Bergen, Bergen, Norway.
³⁷ Division of Psychiatry, Haukeland University Hospital, Bergen, Norway.
³⁸ Center for MR Research, University Children's Hospital Zurich, University of Zurich, Zurich, Switzerland.
³⁹ Interdisciplinary Center Psychopathology and Emotion Regulation, Department of Psychiatry, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
⁴⁰ Department of Child and Adolescent Psychiatry and Psychology, Neuroscience Institute, Hospital Clinic, Barcelona, Spain.
⁴¹ School of Medicine, University of Barcelona, Barcelona, Spain.
⁴² Centro de Investigación Biomédica en Red Salud Mental (CIBERSAM), Barcelona, Spain.
⁴³ Institute d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.
⁴⁴ Department of Psychiatry, Trinity College Dublin, Dublin, Ireland.
⁴⁵ IRCCS Stella Maris Foundation, Pisa, Italy.
⁴⁶ Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.
⁴⁷ Department of Psychiatry, UNIFESP, São Paulo, Brazil.
⁴⁸ Department of Education, ICT and Learning, Østfold University College, Halden, Norway.
⁴⁹ Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
⁵⁰ Lifespan Brain Institute, University of Pennsylvania & Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
⁵¹ Center for Biomedical Image Computing and Analytics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
⁵² Department of Psychiatry, Faculty of Medicine, University of São Paulo, São Paulo, Brazil.
⁵³ Department of Psychiatry and Center for ADHD Research, Oregon Health & Science University, Portland, Oregon, USA.
⁵⁴ Department of Psychiatry, The Penn-CHOP Lifespan Brain Institute, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
⁵⁵ Pisa Division, National Institute for Nuclear Physics (INFN), Pisa, Italy.
⁵⁶ The Hospital for Sick children, Toronto, Canada.
⁵⁷ The Centre for Addiction and Mental Health Toronto, Toronto, Canada.
⁵⁸ Department of Psychiatry, University of Toronto, Toronto, Canada.
⁵⁹ Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
⁶⁰ Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
⁶¹ Mental Illness Research, Education and Clinical Center (MIRECC), James J. Peters VA Medical Center, New York, New York, USA.
⁶² Swedish Collegium for Advanced Study (SCAS), Uppsala, Sweden.
⁶³ Department of Child and Adolescent Psychiatry & Accare Child Study Center, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
⁶⁴ Holland Bloorview Kids Rehabilitation Hospital, Department of Pediatrics, Temetry School of Medicine, University of Toronto, Toronto, Canada.
⁶⁵ Karakter University Center for Child and Adolescent Psychiatry, Nijmegen, The Netherlands.
⁶⁶ Donders Center for Cognitive Neuroimaging, Nijmegen, The Netherlands.
⁶⁷ Radboud University Medical Center, Nijmegen, The Netherlands.
⁶⁸ New York State Psychiatric Institute/CUIMC, New York, New York, USA.
⁶⁹ Division of Child and Adolescent Psychiatry, Department of Psychiatry, University Hospital Lausanne, Lausanne, Switzerland.
⁷⁰ Pediatric OCD Consultation Clinic, SJH, Hamilton, Canada.
⁷¹ Department of Psychiatry and Behavioral Neurosciences and Offord Child Studies, McMaster University, Hamilton, Canada.
⁷² Department of Psychiatry, University of Oxford, Oxford, UK.
⁷³ Trinity College Dublin, Dublin, Ireland.
⁷⁴ School of Psychological Sciences and Turner Institute for Brain and Mental Health, Monash University, Melbourne, Australia.
⁷⁵ Graduate Program of Psychiatry and Behavioral Sciences, Universidade Federal do Rio Grande do Sul, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil.
⁷⁶ Child Mind Institute, New York, New York, USA.
⁷⁷ Department of Child and Adolescent Psychiatry, Institute of Psychiatry and Mental Health, Hospital General Universitario Gregorio Marañón, IiSGM, CIBERSAM, Madrid, Spain.
⁷⁸ Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, Canada.
⁷⁹ Temerty Faculty of Medicine, Department of Psychiatry, University of Toronto, Toronto, Canada.
⁸⁰ Academic Center Child and Youth Psychiatry, Levvel, Amsterdam, The Netherlands.
⁸¹ Department of Child and Adolescent Psychiatry, AmsterdamUMC, Amsterdam, The Netherlands.
⁸² Magnetic Resonance Image Core Facility, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.
⁸³ Department of Psychiatry and Behavioral Sciences, Boston Children's Hospital, Boston, Massachusetts, USA.
⁸⁴ Department of Psychiatry, Harvard Medical School, Boston, Massachusetts, USA.
⁸⁵ Laboratory of Psychiatric Neuroimaging (LIM-21), Departamento e Instituto de Psiquiatria, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, Brazil.
⁸⁶ Atrium Health Wake Forest Baptist Medical Center, Winston-Salem, North Carolina, USA.
⁸⁷ Division of Psychological and Social Medicine and Developmental Neurosciences & Department of Child and Adolescent Psychiatry, Faculty of Medicine, TU Dresden, Dresden, Germany.
⁸⁸ Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
⁸⁹ National Institutes of Health/National Institute of Mental Health, Bethesda, Maryland, USA.
⁹⁰ Centre for Integrative Neuroscience and Neurodynamics, School of Psychology and Clinical Language Sciences, University of Reading, Reading, UK.
⁹¹ Department of Child and Adolescent Psychiatry, Institute of Psychiatry and Mental Health, Hospital General Universitario Gregorio Marañón, IiSGM, School of Medicine, Universidad Complutense, CIBERSAM, Madrid, Spain.
⁹² Department of Psychology and Behavioral Sciences, Zhejiang University, Hangzhou, China.
⁹³ Department of Psychiatry of Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China.
⁹⁴ QIMR Berghofer Medical Research Institute, Herston, Australia.
⁹⁵ Imaging Genetics Center, Mark and Mary Stevens Neuroimaging and Informatics Institute, Keck School of Medicine, University of Southern California, Marina del Rey, California, USA.
⁹⁶ Tommy Fuss Center for Neuropsychiatric Disease Research, Boston Children's Hospital, Boston, Massachusetts, USA.
⁹⁷ Department of Women's and Children's Health, Uppsala University, Uppsala, Sweden.
⁹⁸ Laboratory of Neuro Imaging, Keck School of Medicine, University of Southern California, Los Angeles, California, USA.

PMID: 39046031
PMCID: PMC11267452
DOI: 10.1002/hbm.26754

Large-scale analysis of structural brain asymmetries during neurodevelopment: Associations with age and sex in 4265 children and adolescents

F Kurth et al. Hum Brain Mapp. 2024.

. 2024 Aug 1;45(11):e26754.

doi: 10.1002/hbm.26754.

Authors

Affiliations

¹ School of Psychology, University of Auckland, Auckland, New Zealand.
² Institute of Diagnostic and Interventional Radiology, Jena University Hospital, Jena, Germany.
³ Language and Genetics Department, Max Planck Institute for Psycholinguistics, Nijmegen, The Netherlands.
⁴ Department of Psychiatry, Amsterdam University Medical Center, Amsterdam, The Netherlands.
⁵ Department of Psychiatry, Radboud University Medical Center, Nijmegen, The Netherlands.
⁶ Department of Human Genetics, Radboud University Medical Center, Nijmegen, The Netherlands.
⁷ Donders Institute for Brain, Cognition and Behaviour, Radboud University, Nijmegen, The Netherlands.
⁸ Donders Institute for Brain, Cognition and Behavior, Department of Cognitive Neuroscience, Radboud University Medical Center, Nijmegen, The Netherlands.
⁹ SAMRC Unit on Risk & Resilience in Mental Disorders, Department of Psychiatry & Neuroscience Institute, University of Cape Town, Cape Town, South Africa.
¹⁰ Department of Cognitive Neuroscience, Radboudumc, Nijmegen, The Netherlands.
¹¹ Center of Neurodevelopmental Disorders (KIND), Centre for Psychiatry Research, Department of Women's and Children's Health, Karolinska Institutet & Stockholm Health Care Services, Region Stockholm, Stockholm, Sweden.
¹² Curtin Autism Research Group, Curtin School of Allied Health, Curtin University, Perth, Australia.
¹³ Institut de neurosciences de la Timone UMR 7289, Aix-Marseille Université & CNRS, Marseille, France.
¹⁴ Holland Bloorview Kids Rehabilitation Hospital, Institute for Biomedical Engineering, University of Toronto, Toronto, Canada.
¹⁵ National Institute of Mental Health and Neuro Sciences (NIMHANS), Bengaluru, India.
¹⁶ Department of Psychiatry, Temerty Faculty of Medicine, University of Toronto, Toronto, Canada.
¹⁷ Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK.
¹⁸ School of Information Technology and Electrical Engineering, The University of Queensland, Brisbane, Australia.
¹⁹ Child and Adolescent Psychiatry Unit, Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
²⁰ BC Children's Research Institute and the University of British Columbia, Vancouver, Canada.
²¹ Department of Psychiatry, Columbia University Irving Medical Center and the New York State Psychiatric Institute, New York, New York, USA.
²² Department & Institute of Psychiatry, University of Sao Paulo, Medical School, Sao Paulo, Brazil.
²³ Department of Methods and Techniques in Psychology, Pontifical Catholic University, Sao Paulo, Brazil.
²⁴ The Mathison Centre for Mental Health Research & Education, Hotchkiss Brain Institute, University of Calgary, Calgary, Canada.
²⁵ Federal University of São Paulo, São Paulo, Brazil.
²⁶ Instituto Ame Sua Mente, São Paulo, Brazil.
²⁷ British Columbia Children's Hospital, British Columbia Mental Health and Substance Use Services, University of British Columbia, Vancouver, Canada.
²⁸ Department of Psychiatry, Yale University, New Haven, Connecticut, USA.
²⁹ Department of Biological and Medical Psychology, University of Bergen, Bergen, Norway.
³⁰ Laboratório de Neurociências Integrativas (LINC), Departamento de Psiquiatria, Universidade Federal de São Paulo (UNIFESP), São Paulo, Brazil.
³¹ Instituto Nacional de siquiatria do Desenvolvimento (INPD), São Paulo, Brazil.
³² Centre for Social and Early Emotional Development and School of Psychology, Deakin University, Geelong, Australia.
³³ Murdoch Children's Research Institute, Melbourne, Australia.
³⁴ Department of Psychiatry, Section on Neurodevelopment and Psychosis and the Lifespan Brain Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
³⁵ Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
³⁶ Department of Biomedicine, University of Bergen, Bergen, Norway.
³⁷ Division of Psychiatry, Haukeland University Hospital, Bergen, Norway.
³⁸ Center for MR Research, University Children's Hospital Zurich, University of Zurich, Zurich, Switzerland.
³⁹ Interdisciplinary Center Psychopathology and Emotion Regulation, Department of Psychiatry, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
⁴⁰ Department of Child and Adolescent Psychiatry and Psychology, Neuroscience Institute, Hospital Clinic, Barcelona, Spain.
⁴¹ School of Medicine, University of Barcelona, Barcelona, Spain.
⁴² Centro de Investigación Biomédica en Red Salud Mental (CIBERSAM), Barcelona, Spain.
⁴³ Institute d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.
⁴⁴ Department of Psychiatry, Trinity College Dublin, Dublin, Ireland.
⁴⁵ IRCCS Stella Maris Foundation, Pisa, Italy.
⁴⁶ Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.
⁴⁷ Department of Psychiatry, UNIFESP, São Paulo, Brazil.
⁴⁸ Department of Education, ICT and Learning, Østfold University College, Halden, Norway.
⁴⁹ Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
⁵⁰ Lifespan Brain Institute, University of Pennsylvania & Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
⁵¹ Center for Biomedical Image Computing and Analytics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
⁵² Department of Psychiatry, Faculty of Medicine, University of São Paulo, São Paulo, Brazil.
⁵³ Department of Psychiatry and Center for ADHD Research, Oregon Health & Science University, Portland, Oregon, USA.
⁵⁴ Department of Psychiatry, The Penn-CHOP Lifespan Brain Institute, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
⁵⁵ Pisa Division, National Institute for Nuclear Physics (INFN), Pisa, Italy.
⁵⁶ The Hospital for Sick children, Toronto, Canada.
⁵⁷ The Centre for Addiction and Mental Health Toronto, Toronto, Canada.
⁵⁸ Department of Psychiatry, University of Toronto, Toronto, Canada.
⁵⁹ Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
⁶⁰ Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
⁶¹ Mental Illness Research, Education and Clinical Center (MIRECC), James J. Peters VA Medical Center, New York, New York, USA.
⁶² Swedish Collegium for Advanced Study (SCAS), Uppsala, Sweden.
⁶³ Department of Child and Adolescent Psychiatry & Accare Child Study Center, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
⁶⁴ Holland Bloorview Kids Rehabilitation Hospital, Department of Pediatrics, Temetry School of Medicine, University of Toronto, Toronto, Canada.
⁶⁵ Karakter University Center for Child and Adolescent Psychiatry, Nijmegen, The Netherlands.
⁶⁶ Donders Center for Cognitive Neuroimaging, Nijmegen, The Netherlands.
⁶⁷ Radboud University Medical Center, Nijmegen, The Netherlands.
⁶⁸ New York State Psychiatric Institute/CUIMC, New York, New York, USA.
⁶⁹ Division of Child and Adolescent Psychiatry, Department of Psychiatry, University Hospital Lausanne, Lausanne, Switzerland.
⁷⁰ Pediatric OCD Consultation Clinic, SJH, Hamilton, Canada.
⁷¹ Department of Psychiatry and Behavioral Neurosciences and Offord Child Studies, McMaster University, Hamilton, Canada.
⁷² Department of Psychiatry, University of Oxford, Oxford, UK.
⁷³ Trinity College Dublin, Dublin, Ireland.
⁷⁴ School of Psychological Sciences and Turner Institute for Brain and Mental Health, Monash University, Melbourne, Australia.
⁷⁵ Graduate Program of Psychiatry and Behavioral Sciences, Universidade Federal do Rio Grande do Sul, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil.
⁷⁶ Child Mind Institute, New York, New York, USA.
⁷⁷ Department of Child and Adolescent Psychiatry, Institute of Psychiatry and Mental Health, Hospital General Universitario Gregorio Marañón, IiSGM, CIBERSAM, Madrid, Spain.
⁷⁸ Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, Canada.
⁷⁹ Temerty Faculty of Medicine, Department of Psychiatry, University of Toronto, Toronto, Canada.
⁸⁰ Academic Center Child and Youth Psychiatry, Levvel, Amsterdam, The Netherlands.
⁸¹ Department of Child and Adolescent Psychiatry, AmsterdamUMC, Amsterdam, The Netherlands.
⁸² Magnetic Resonance Image Core Facility, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.
⁸³ Department of Psychiatry and Behavioral Sciences, Boston Children's Hospital, Boston, Massachusetts, USA.
⁸⁴ Department of Psychiatry, Harvard Medical School, Boston, Massachusetts, USA.
⁸⁵ Laboratory of Psychiatric Neuroimaging (LIM-21), Departamento e Instituto de Psiquiatria, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, Brazil.
⁸⁶ Atrium Health Wake Forest Baptist Medical Center, Winston-Salem, North Carolina, USA.
⁸⁷ Division of Psychological and Social Medicine and Developmental Neurosciences & Department of Child and Adolescent Psychiatry, Faculty of Medicine, TU Dresden, Dresden, Germany.
⁸⁸ Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
⁸⁹ National Institutes of Health/National Institute of Mental Health, Bethesda, Maryland, USA.
⁹⁰ Centre for Integrative Neuroscience and Neurodynamics, School of Psychology and Clinical Language Sciences, University of Reading, Reading, UK.
⁹¹ Department of Child and Adolescent Psychiatry, Institute of Psychiatry and Mental Health, Hospital General Universitario Gregorio Marañón, IiSGM, School of Medicine, Universidad Complutense, CIBERSAM, Madrid, Spain.
⁹² Department of Psychology and Behavioral Sciences, Zhejiang University, Hangzhou, China.
⁹³ Department of Psychiatry of Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China.
⁹⁴ QIMR Berghofer Medical Research Institute, Herston, Australia.
⁹⁵ Imaging Genetics Center, Mark and Mary Stevens Neuroimaging and Informatics Institute, Keck School of Medicine, University of Southern California, Marina del Rey, California, USA.
⁹⁶ Tommy Fuss Center for Neuropsychiatric Disease Research, Boston Children's Hospital, Boston, Massachusetts, USA.
⁹⁷ Department of Women's and Children's Health, Uppsala University, Uppsala, Sweden.
⁹⁸ Laboratory of Neuro Imaging, Keck School of Medicine, University of Southern California, Los Angeles, California, USA.

PMID: 39046031
PMCID: PMC11267452
DOI: 10.1002/hbm.26754

Abstract

Only a small number of studies have assessed structural differences between the two hemispheres during childhood and adolescence. However, the existing findings lack consistency or are restricted to a particular brain region, a specific brain feature, or a relatively narrow age range. Here, we investigated associations between brain asymmetry and age as well as sex in one of the largest pediatric samples to date (n = 4265), aged 1-18 years, scanned at 69 sites participating in the ENIGMA (Enhancing NeuroImaging Genetics through Meta-Analysis) consortium. Our study revealed that significant brain asymmetries already exist in childhood, but their magnitude and direction depend on the brain region examined and the morphometric measurement used (cortical volume or thickness, regional surface area, or subcortical volume). With respect to effects of age, some asymmetries became weaker over time while others became stronger; sometimes they even reversed direction. With respect to sex differences, the total number of regions exhibiting significant asymmetries was larger in females than in males, while the total number of measurements indicating significant asymmetries was larger in males (as we obtained more than one measurement per cortical region). The magnitude of the significant asymmetries was also greater in males. However, effect sizes for both age effects and sex differences were small. Taken together, these findings suggest that cerebral asymmetries are an inherent organizational pattern of the brain that manifests early in life. Overall, brain asymmetry appears to be relatively stable throughout childhood and adolescence, with some differential effects in males and females.

Keywords: ENIGMA; adolescence; age; asymmetry; brain; childhood; cortical thickness; development; gender; gray matter; sex.

PubMed Disclaimer

Conflict of interest statement

Paul Arnold receives research support from Biohaven Pharmaceuticals. Sven Bölte acted as an author, consultant or lecturer for Medice and Roche over the past 3 years. In addition, he receives royalties for textbooks and diagnostic tools from Hogrefe and Liber, and he is partner at NeuroSupportSolutions International AB. Rodrigo Bressan received personal fees from Sanofi, Ache, as well as institutional grants, personal fees and non‐financial support from Janssen unrelated to this manuscript. Barbara Franke and Martine Hoogman have received educational speaking fees from Medice. Azadeh Kushki has a patent for Anxiety Meter with royalties paid from Awake Labs. Pedro Pan received payment or honoraria for lectures and presentations in educational events for Sandoz, Daiichi Sankyo, Eurofarma, Abbot, Libbs, Instituto Israelita de Pesquisa e Ensino Albert Einstein, Instituto D'Or de Pesquisa e Ensino. Katya Rubia has received a grant from Takeda pharmaceuticals for an unrelated project and consulting fees from Supernus and Lundbeck. Lin Sorensen received a fee for speaking and conference support in 2023 from Medice Nordic Norway. Paul Thompson and Neda Jahanshad were funded in part by a research grant from Biogen, Inc., for research unrelated to this manuscript. Blair Simpson has received royalties from UpToDate, Inc., and a stipend from the American Medical Association for her role as Associate Editor at JAMA Psychiatry. Celso Arango has been a consultant to or has received honoraria or grants from Acadia, Angelini, Biogen, Boehringer, Gedeon Richter, Janssen Cilag, Lundbeck, Medscape, Menarini, Minerva, Otsuka, Pfizer, Roche, Sage, Servier, Shire, Schering Plough, Sumitomo Dainippon Pharma, Sunovion and Takeda.

Figures

**FIGURE 1**
Hemispheric asymmetry. Cortical regions with significant asymmetries are indicated in green. The regions defined by the Desikan–Killiany atlas (Desikan et al., 2006) were projected onto the central surface of the FSAverage template using the CAT12 toolbox (Gaser et al., 2022). Rightward asymmetries are indicated on the right hemispheres, leftward asymmetries on the left hemispheres. All significant asymmetries are FDR‐corrected using a threshold of 0.05 (Benjamini & Yekutieli, ; Hochberg & Benjamini, 1990).

**FIGURE 2**
Age‐related changes in asymmetry. Cortical regions with significant age‐related changes in asymmetry are indicated in orange (increases) or cyan (decreases). Rightward asymmetries are indicated on the right hemispheres, leftward asymmetries on the left hemispheres. If asymmetry for a specific region changes in its direction with increasing age, the region is indicated in both left and right panels.

**FIGURE 3**
Sex differences in asymmetry. Cortical regions with significantly larger asymmetries in males are depicted in blue, and with significantly larger asymmetries in females in red. Rightward asymmetries are indicated on the right hemispheres, leftward asymmetries on the left hemispheres.

See this image and copyright information in PMC

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Wu X, Zhang K, Kuang N, Kong X, Cao M, Lian Z, Liu Y, Fan H, Yu G, Liu Z, Cheng W, Jia T, Sahakian BJ, Robbins TW, Feng J, Schumann G, Palaniyappan L, Zhang J. Wu X, et al. Nat Commun. 2025 May 14;16(1):4480. doi: 10.1038/s41467-025-59110-9. Nat Commun. 2025. PMID: 40368909

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Large-scale analysis of structural brain asymmetries during neurodevelopment: Associations with age and sex in 4265 children and adolescents

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Large-scale analysis of structural brain asymmetries during neurodevelopment: Associations with age and sex in 4265 children and adolescents

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