Subcortical volumes across the lifespan: Data from 18,605 healthy individuals aged 3–90 years

RESEARCH ARTICLE Subcortical volumes across the lifespan: Data from 18,605 healthy individuals aged 3–90 years Danai Dima 1,2 | Amirhossein Modabbernia 3 | Efstathios Papachristou 4 | Gaelle E. Doucet 5 | Ingrid Agartz 6,7,8 | Moji Aghajani 9,10 | Theophilus N. Akudjedu 11,12 | Anton Albajes-Eizagirre 13,14 | Dag Alnæs 6,15 | Kathryn I. Alpert 16 | Micael Andersson 17 | Nancy C. Andreasen 18 | Ole A. Andreassen 6 | Philip Asherson 19 | Tobias Banaschewski 20 | Nuria Bargallo 21,22 | Sarah Baumeister 20 | Ramona Baur-Streubel 23 | Alessandro Bertolino 24 | Aurora Bonvino 24 | Dorret I. Boomsma 25 | Stefan Borgwardt 26 | Josiane Bourque 27 | Daniel Brandeis 20 | Alan Breier 28 | Henry Brodaty 29 | Rachel M. Brouwer 30 | Jan K. Buitelaar 31,32,33 | Geraldo F. Busatto 34 | Randy L. Buckner 35,36 | Vincent Calhoun 37 | Erick J. Canales-Rodríguez 13,14 | Dara M. Cannon 12 | Xavier Caseras 38 | Francisco X. Castellanos 39 | Simon Cervenka 8,40 | Tiffany M. Chaim-Avancini 34 | Christopher R. K. Ching 41 | Victoria Chubar 42 | Vincent P. Clark 43,44 | Patricia Conrod 45 | Annette Conzelmann 46 | Benedicto Crespo-Facorro 14,47 | Fabrice Crivello 48 | Eveline A. Crone 49,50 | Udo Dannlowski 51 | Anders M. Dale 52 | Christopher Davey 53 | Eco J. C. de Geus 25 | Lieuwe de Haan 54 | Greig I. de Zubicaray 55 | Anouk den Braber 25 | Erin W. Dickie 56,57 | Annabella Di Giorgio 58 | Nhat Trung Doan 6 | Erlend S. Dørum 6,59,60 | Stefan Ehrlich 61,62 | Susanne Erk 63 | Thomas Espeseth 59,64 | Helena Fatouros-Bergman 8,40 | Simon E. Fisher 33,65 | Jean-Paul Fouche 66 | Barbara Franke 33,67,68 | Thomas Frodl 69 | Paola Fuentes-Claramonte 13,14 | David C. Glahn 70 | Ian H. Gotlib 71 | Hans-Jörgen Grabe 72,73 | Oliver Grimm 74 | Nynke A. Groenewold 66,75 | Dominik Grotegerd 75 | Oliver Gruber 76 | Patricia Gruner 77,78 | Rachel E. Gur 27,79,80 | Ruben C. Gur 27,79,80 | Tim Hahn 51 | Ben J. Harrison 81 | Catharine A. Hartman 82 | † Members of the Karolinska Schizophrenia Project (KaSP): Göran Engberg 1 , Sophie Erhardt 1 , Lilly Schwieler 1 , Funda Orhan 1 , Anna Malmqvist 1 , Mikael Hedberg 1 , Lars Farde 2 , Simon Cervenka 2 , Lena Flyckt 5 , Karin Collste 2 , Pauliina Ikonen 2 , Fredrik Piehl 3 , Ingrid Agartz 4,5 1 Department of Physiology and Pharmacology, Karolinska Institute, Sweden; 2 Department of Clinical Neuroscience, Center for Psychiatry Research, Karolinska Institutet, Sweden; 3 Neuroimmunology Unit, Department of Clinical Neuroscience, Karolinska Institutet, Sweden; 4 NORMENT, Division of Mental Health and Addiction, KG Jebsen Centre for Psychosis Research, University of Oslo and Department of Psychiatric Research, Diakonhjemmet Hospital, Norway; 5 Center for Psychiatric Research, Department of Clinical Neuroscience, Karolinska Institutet, Sweden. Received: 22 June 2020 Revised: 27 November 2020 Accepted: 6 December 2020 DOI: 10.1002/hbm.25320 This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. © 2021 The Authors. Human Brain Mapping published by Wiley Periodicals LLC. 452 Hum Brain Mapp. 2022;43:452–469.wileyonlinelibrary.com/journal/hbm Sean N. Hatton 83 | Andreas Heinz 62 | Dirk J. Heslenfeld 84 | Derrek P. Hibar 85 | Ian B. Hickie 83 | Beng-Choon Ho 18 | Pieter J. Hoekstra 86 | Sarah Hohmann 20 | Avram J. Holmes 87 | Martine Hoogman 33,66 | Norbert Hosten 88 | Fleur M. Howells 65,74 | Hilleke E. Hulshoff Pol 30 | Chaim Huyser 89 | Neda Jahanshad 41 | Anthony James 90 | Terry L. Jernigan 91 | Jiyang Jiang 29 | Erik G. Jönsson 6,8,40 | John A. Joska 65 | Rene Kahn 3 | Andrew Kalnin 92 | Ryota Kanai 93 | Marieke Klein 33,66,94 | Tatyana P. Klyushnik 95 | Laura Koenders 53 | Sanne Koops 30 | Bernd Krämer 76 | Jonna Kuntsi 19 | Jim Lagopoulos 96 | Luisa Lázaro 97,14 | Irina Lebedeva 95 | Won Hee Lee 3 | Klaus-Peter Lesch 98 | Christine Lochner 99 | Marise W. J. Machielsen 53 | Sophie Maingault 48 | Nicholas G. Martin 100 | Ignacio Martínez-Zalacaín 14,101 | David Mataix-Cols 8,40 | Bernard Mazoyer 48 | Colm McDonald 12 | Brenna C. McDonald 28 | Andrew M. McIntosh 102 | Katie L. McMahon 103 | Genevieve McPhilemy 12 | Susanne Meinert 51 | José M. Menchón 14,101 | Sarah E. Medland 100 | Andreas Meyer-Lindenberg 104 | Jilly Naaijen 32,33 | Pablo Najt 12 | Tomohiro Nakao 105 | Jan E. Nordvik 106 | Lars Nyberg 17,107 | Jaap Oosterlaan 108 | Víctor Ortiz-García de la Foz 14,109,110 | Yannis Paloyelis 2 | Paul Pauli 23,111 | Giulio Pergola 24 | Edith Pomarol-Clotet 13,14 | Maria J. Portella 13,112 | Steven G. Potkin 113 | Joaquim Radua 8,22,114 | Andreas Reif 73 | Daniel A. Rinker 6 | Joshua L. Roffman 36 | Pedro G. P. Rosa 34 | Matthew D. Sacchet 115 | Perminder S. Sachdev 29 | Raymond Salvador 13 | Pascual Sánchez-Juan 109,116 | Salvador Sarró 13 | Theodore D. Satterthwaite 27 | Andrew J. Saykin 28 | Mauricio H. Serpa 34 | Lianne Schmaal 117,118 | Knut Schnell 119 | Gunter Schumann 19,120 | Kang Sim 121 | Jordan W. Smoller 122 | Iris Sommer 123 | Carles Soriano-Mas 14,101 | Dan J. Stein 99 | Lachlan T. Strike 124 | Suzanne C. Swagerman 25 | Christian K. Tamnes 6,7,125 | Henk S. Temmingh 65 | Sophia I. Thomopoulos 41 | Alexander S. Tomyshev 95 | Diana Tordesillas-Gutiérrez 13,126 | Julian N. Trollor 29 | Jessica A. Turner 127 | Anne Uhlmann 65 | Odile A. van den Heuvel 9 | Dennis van den Meer 6,15,128 | Nic J. A. van der Wee 129,130 | Neeltje E. M. van Haren 131 | Dennis van't Ent 25 | Theo G. M. van Erp 132,113,133 | Ilya M. Veer 62 | Dick J. Veltman 9 | Aristotle Voineskos 55,56 | Henry Völzke 133,134,135 | Henrik Walter 62 | Esther Walton 136 | Lei Wang 137 | Yang Wang 138 | Thomas H. Wassink 18 | Bernd Weber 139 | Wei Wen 29 | John D. West 28 | Lars T. Westlye 58 | Heather Whalley 102 | Lara M. Wierenga 140 | Steven C. R. Williams 2 | Katharina Wittfeld 71,72 | Daniel H. Wolf 27 | Amanda Worker 2 | Margaret J. Wright 124 | Kun Yang 141 | Yulyia Yoncheva 142 | Marcus V. Zanetti 34,143 | Georg C. Ziegler 144 | Paul M. Thompson 41 | DIMA ET AL.453 Sophia Frangou 3,145 | Karolinska Schizophrenia Project (KaSP) 1 Department of Psychology, School of Arts and Social Sciences, City University of London, London, UK 2 Department of Neuroimaging, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK 3 Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, New York 4 Psychology and Human Development, Institute of Education, University College London, London, UK 5 Boys Town National Research Hospital, Omaha, Nebraska 6 Norwegian Centre for Mental Disorders Research (NORMENT), Institute of Clinical Medicine, University of Oslo, Oslo, Norway 7 Department of Psychiatric Research, Diakonhjemmet Hospital, Oslo, Norway 8 Centre for Psychiatric Research, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden 9 Department of Psychiatry, Amsterdam University Medical Centre, Location VUmc, Amsterdam, Netherlands 10 Institute of Education & Child Studies, Section Forensic Family & Youth Care, Leiden University, Netherlands 11 Institute of Medical Imaging and Visualisation, Department of Medical Science and Public Health, Faculty of Health and Social Sciences, Bournemouth University, Poole, UK 12 Clinical Neuroimaging Laboratory, Centre for Neuroimaging and Cognitive Genomics and NCBES Galway Neuroscience Centre, National University of Ireland, Dublin, Ireland 13 FIDMAG Germanes Hospitalàries, Madrid, Spain 14 Mental Health Research Networking Center (CIBERSAM), Madrid, Spain 15 Division of Mental Health and Addiction, Institute of Clinical Medicine, University of Oslo, Oslo, Norway 16 Radiologics, Inc, Chicago, Illinois 17 Department of Integrative Medical Biology, Umeå University, Umeå, Sweden 18 Department of Psychiatry, Carver College of Medicine, The University of Iowa, Iowa City, Iowa 19 Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK 20 Department of Child and Adolescent Psychiatry and Psychotherapy, Central Institute of Mental Health, Heidelberg University, Mannheim, Germany 21 Imaging Diagnostic Centre, Hospital Clinic, Barcelona University Clinic, Barcelona, Spain 22 August Pi i Sunyer Biomedical Research Institut (IDIBAPS), Barcelona, Spain 23 Department of Psychology, Biological Psychology, Clinical Psychology and Psychotherapy, University of Würzburg, Wurzburg, Germany 24 Department of Basic Medical Science, Neuroscience and Sense Organs, University of Bari Aldo Moro, Bari, Italy 25 Department of Biological Psychology, Vrije Universiteit, Amsterdam, Netherlands 26 Department of Psychiatry & Psychotherapy, University of Lübeck, Lubeck, Germany 27 Department of Psychiatry, University of Pennsylvania, Philadelphia, Pennsylvania 28 Department of Radiology and Imaging Sciences, Indiana University School of Medicine, Indianapolis, Indiana 29 Centre for Healthy Brain Ageing, School of Psychiatry, University of New South Wales, Sydney, Australia 30 Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, Utrecht, Netherlands 31 Donders Center of Medical Neurosciences, Radboud University, Nijmegen, Netherlands 32 Donders Centre for Cognitive Neuroimaging, Radboud University, Nijmegen, Netherlands 33 Donders Institute for Brain, Cognition and Behaviour, Radboud University, Nijmegen, Netherlands 34 Laboratory of Psychiatric Neuroimaging, Departamento e Instituto de Psiquiatria, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de S~ ao Paulo, S~ ao Paulo, Brazil 35 Department of Psychology, Center for Brain Science, Harvard University, Cambridge, Massachusetts 36 Department of Psychiatry, Massachusetts General Hospital, Boston, Massachusetts 37 Tri-Institutional Center for Translational Research in Neuroimaging and Data Science (TReNDS), Georgia State University, Georgia Institute of Technology, Emory University, USA Neurology, Radiology, Psychiatry and Biomedical Engineering, Emory University, Atlanta, Georgia 38 MRC Centre for Neuropsychiatric Genetics and Genomics, Cardiff University, Cardiff, UK 39 Department of Child and Adolescent Psychiatry, New York University, New York, New York 40 Stockholm Health Care Services, Stockholm Region, Stockholm, Sweden 41 Imaging Genetics Center, Mark and Mary Stevens Neuroimaging and Informatics Institute, Keck School of Medicine, University of Southern California, Los Angeles, California 42 Department of Neuroscience, KU Leuven, Mind-Body Research Group, Leuven, Belgium 43 Department of Psychology, University of New Mexico, Albuquerque, New Mexico 454 DIMA ET AL. 44 Mind Research Network, Albuquerque, New Mexico 45 Department of Psychiatry, Université de Montréal, Montreal, Canada 46 Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, University of Tübingen, Tubingen, Germany 47 HU Virgen del Rocio, IBiS, University of Sevilla, Sevilla, Spain 48 Groupe d'Imagerie Neurofonctionnelle, Institut des Maladies Neurodégénératives, UMR5293, Université de Bordeaux, Talence, France 49 Erasmus School of Social and Behavioural Sciences, Erasmus University Rotterdam, Rotterdam, Netherlands 50 Faculteit der Sociale Wetenschappen, Instituut Psychologie, Universiteit Leiden, Leiden, Netherlands 51 Department of Psychiatry and Psychotherapy, University of Münster, Munster, Germany 52 Center for Multimodal Imaging and Genetics, Department of Neuroscience and Department of Radiology, University of California-San Diego, La Jolla, California 53 Department of Psychiatry, University of Melbourne, Melbourne, Australia 54 Academisch Medisch Centrum, Universiteit van Amsterdam, Amsterdam, Netherlands 55 Faculty of Health, Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Australia 56 Kimel Family Translational Imaging Genetics Laboratory, Campbell Family Mental Health Research Institute, CAMH, Toronto, Canada 57 Department of Psychiatry, University of Toronto, Toronto, Canada 58 Biological Psychiatry Lab, Fondazione IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo (FG), Italy 59 Department of Psychology, University of Oslo, Oslo, Norway 60 Sunnaas Rehabilitation Hospital HT, Nesodden, Norway 61 Division of Psychological and Social Medicine and Developmental Neurosciences, Technische Universität Dresden, Dresden, Germany 62 Faculty of Medicine, Universitätsklinikum Carl Gustav Carus an der TU Dresden, Dresden, Germany 63 Division of Mind and Brain Research, Department of Psychiatry and Psychotherapy, Charité-Universitätsmedizin Berlin, Berlin, Germany 64 Bjørknes College, Oslo, Norway 65 Language and Genetics Department, Max Planck Institute for Psycholinguistics, Nijmegen, Netherlands 66 Department of Psychiatry and Mental Health, University of Cape Town, Rondebosch, South Africa 67 Department of Human Genetics, Radboud University Medical Center, Nijmegen, Netherlands 68 Department of Psychiatry, Radboud University Medical Center, Nijmegen, Netherlands 69 Department of Psychiatry and Psychotherapy, Otto von Guericke University Magdeburg, Magdeburg, Germany 70 Department of Psychiatry, Tommy Fuss Center for Neuropsychiatric Disease Research Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts 71 Department of Psychology, Stanford University, Stanford, California 72 Department of Psychiatry and Psychotherapy, University Medicine Greifswald, University of Greifswald, Greifswald, Germany 73 German Center for Neurodegenerative Diseases (DZNE), Site Rostock/Greifswald, Greifswald, Germany 74 Department for Psychiatry, Psychosomatics and Psychotherapy, Universitätsklinikum Frankfurt, Goethe Universitat, Frankfurt, Germany 75 Neuroscience Institute, University of Cape Town, Rondebosch, South Africa 76 Section for Experimental Psychopathology and Neuroimaging, Department of General Psychiatry, Heidelberg University, Heidelberg, Germany 77 Department of Psychiatry, Yale University, New Haven, Connecticut 78 Learning Based Recovery Center, VA Connecticut Health System, New Haven, Connecticut 79 Lifespan Brain Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 80 Children's Hospital of Philadelphia, University of Pennsylvania, Philadelphia, Pennsylvania 81 Melbourne Neuropsychiatry Center, University of Melbourne, Melbourne, Australia 82 Interdisciplinary Center Psychopathology and Emotion regulation, University Medical Center Groningen, University of Groningen, Groningen, Netherlands 83 Brain and Mind Centre, University of Sydney, Sydney, Australia 84 Departments of Experimental and Clinical Psychology, Vrije Universiteit Amsterdam, Amsterdam, Netherlands 85 Personalized Healthcare, Genentech, Inc, South San Francisco, California 86 Department of Psychiatry, University Medical Center Groningen, University of Groningen, Groningen, Netherlands 87 Department of Psychology, Yale University, New Haven, Connecticut 88 Norbert Institute of Diagnostic Radiology and Neuroradiology, University Medicine Greifswald, University of Greifswald, Greifswald, Germany 89 Bascule, Academic Centre for Children and Adolescent Psychiatry, Duivendrecht, Netherlands 90 Department of Psychiatry, Oxford University, Oxford, UK 91 Center for Human Development, Departments of Cognitive Science, Psychiatry, and Radiology, University of California, San Diego, California 92 Department of Radiology, Ohio State University College of Medicine, Columbus, Ohio DIMA ET AL.455 93 Department of Neuroinformatics, Araya, Inc, Tokyo, Japan 94 Department of Psychiatry, University of California San Diego, La Jolla, California 95 Mental Health Research Center, Russian Academy of Medical Sciences, Moskva, Russia 96 Sunshine Coast Mind and Neuroscience, Thompson Institute, University of the Sunshine Coast, Sunshine Coast, Australia 97 Department of Child and Adolescent Psychiatry and Psychology, Hospital Clinic, University of Barcelona, Barcelona, Spain 98 Department of Psychiatry, Psychosomatics and Psychotherapy, Julius-Maximilians Universität Würzburg, Wurzburg, Germany 99 SA MRC Unit on Risk and Resilience in Mental Disorders, Department of Psychiatry, Stellenbosch University, Stellenbosch, South Africa 100 Queensland Institute of Medical Research, Berghofer Medical Research Institute, Brisbane, Australia 101 Department of Psychiatry, Bellvitge University Hospital-IDIBELL, University of Barcelona, Barcelona, Spain 102 Division of Psychiatry, University of Edinburgh, Edinburgh, UK 103 School of Clinical Sciences, Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Australia 104 Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, Heidelberg University, Heidelberg, Germany 105 Department of Clinical Medicine, Kyushu University, Kyushu, Japan 106 CatoSenteret Rehabilitation Hospital, Son, Norway 107 Department of Radiation Sciences, Umeå Center for Functional Brain Imaging, Umeå University, Umeå, Sweden 108 Department of Clinical Neuropsychology, Amsterdam University Medical Centre, Vrije Universiteit Amsterdam, Amsterdam, Netherlands 109 Department of Psychiatry, University Hospital “Marques de Valdecilla”, Instituto de Investigación Valdecilla (IDIVAL), Santander, Spain 110 Instituto de Salud Carlos III, Madrid, Spain 111 Centre of Mental Health, University of Würzburg, Wurzburg, Germany 112 Department of Psychiatry, Hospital de la Santa Creu i Sant Pau, Institut d'Investigació Biomèdica Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain 113 Department of Psychiatry, University of California at Irvine, Irvine, California 114 Department of Psychosis Studies, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK 115 Center for Depression, Anxiety, and Stress Research, McLean Hospital, Harvard Medical School, Boston, Massachusetts 116 Centro de Investigacion Biomedica en Red en Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain 117 Orygen, The National Centre of Excellence in Youth Mental Health, Parkville, Australia 118 Centre for Youth Mental Health, The University of Melbourne, Melbourne, Australia 119 Department of Psychiatry and Psychotherapy, University Medical Center Göttingen, Göttingen, Germany 120 Centre for Population Neuroscience and Precision Medicine, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK 121 Institute of Mental Health, Singapore, Singapore 122 Center for Genomic Medicine, Massachusetts General Hospital, Boston, Massachusetts 123 Department of Biomedical Sciences of Cells and Systems, Rijksuniversiteit Groningen, University Medical Center Groningen, Göttingen, Netherlands 124 Queensland Brain Institute, University of Queensland, Brisbane, Australia 125 PROMENTA Research Center, Department of Psychology, University of Oslo, Oslo, Norway 126 Neuroimaging Unit, Technological Facilities, Valdecilla Biomedical Research Institute IDIVAL, Santander, Spain 127 College of Arts and Sciences, Georgia State University, Atlanta, Georgia 128 School of Mental Health and Neuroscience, Faculty of Health, Medicine and Life Sciences, Maastricht University, Maastricht, Netherlands 129 Department of Psychiatry, Leiden University Medical Center, Leiden, Netherlands 130 Leiden Institute for Brain and Cognition, Leiden, Netherlands 131 Department of Child and Adolescent Psychiatry/Psychology, Erasmus University Medical Center, Sophia Children's Hospital, Rotterdam, The Netherlands 132 Center for the Neurobiology of Learning and Memory, University of California Irvine, Irvine, California 133 Institute of Community Medicine, University Medicine, Greifswald, University of Greifswald, Greifswald, Germany 134 German Centre for Cardiovascular Research (DZHK), partner site Greifswald, Greifswald, Germany 135 German Center for Diabetes Research (DZD), partner site Greifswald, Greifswald, Germany 136 Department of Psychology, University of Bath, Bath, UK 137 Department of Psychiatry and Behavioral Sciences, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 138 Department of Radiology, Medical College of Wisconsin, Milwaukee, Wisconsin 139 Institute for Experimental Epileptology and Cognition Research, University of Bonn, Bonn, Germany 140 Developmental and Educational Psychology Unit, Institute of Psychology, Leiden University, Leiden, Netherlands 141 National High Magnetic Field Laboratory, Florida State University, Tallahassee, Florida 456 DIMA ET AL. 142 Department of Child and Adolescent Psychiatry, Child Study Center, NYU Langone Health, New York, New York 143 Instituto de Ensino e Pesquisa, Hospital Sírio-Libanês, S~ ao Paulo, Brazil 144 Division of Molecular Psychiatry, Center of Mental Health, University of Würzburg, Wurzburg, Germany 145 Department of Psychiatry, Djavad Mowafaghian Centre for Brain Health, University of British Columbia, Vancouver, Canada Correspondence Sophia Frangou, Department of Psychiatry, Icahn School of Medicine at Mount Sinai, 1425 Madison Avenue, New York, New York 10029, USA. Email: [email protected] Danai Dima, University of London, Northampton Square, London EC1V 0HB, UK. Email: [email protected] Funding information National Institute of Mental Health, Grant/ Award Numbers: MH104284, MH116147, R01MH113619, R01 MH090553, R01MH117014, R01MH042191; Karolinska Institutet; Stockholm County Council; Southern and Eastern Norway Regional Health Authority; German Centre for Cardiovascular Research; DZHK; Siemens Healthineers; University of Queensland; US National Institute of Child Health and Human Development, Grant/Award Number: RO1HD050735; Australian National Health and Medical Research Council; Eunice Kennedy Shriver National Institute of Child Health & Human Development; National Institute on Drug Abuse, Grant/Award Numbers: UL1 TR000153, 1 U24 RR025736-01, 1 U24 RR021992; Brain Injury Fund Research Grant Program; Indiana State Department of Health Spinal Cord; Parents Against Childhood Epilepsy; Epilepsy Therapy Project, Fight Against Childhood Epilepsy and Seizures; Epilepsy Foundation; American Epilepsy Society; Knut and Alice Wallenberg Foundation; European Community's Horizon 2020 Programme; Vici Innovation Program; NWO Brain & Cognition Excellence Program; Netherlands Organization for Scientific Research; Hersenstichting Nederland; Netherlands Organization for Health Research and Development; Geestkracht Programme of the Dutch Health Research Council, Grant/ Award Number: 10-000-1001; Universiteit Utrecht; FP7 Ideas: European Research Council; Nederlandse Organisatie voor Wetenschappelijk Onderzoek; National Center for Advancing Translational Sciences; National Institutes of Health; National Center for Research Resources; Consortium grant, Grant/ Award Number: U54 EB020403; U.S. National Institutes of Health, Grant/Award Numbers: R01 CA101318, P30 AG10133, R01 AG19771; Medical Research Council, Grant/ Award Number: G0500092; Fundación Instituto de Investigación Marqués de Valdecilla, Grant/Award Numbers: API07/011, NCT02534363, NCT0235832; Instituto de Salud Carlos III, Grant/Award Numbers: PI14/00918, PI14/00639, PI060507, Abstract Age has a major effect on brain volume. However, the normative studies available are constrained by small sample sizes, restricted age coverage and significant methodological variability. These limitations introduce inconsistencies and may obscure or distort the lifespan trajectories of brain morphometry. In response, we capitalized on the resources of the Enhancing Neuroimaging Genetics through Meta-Analysis (ENIGMA) Consortium to examine age-related trajectories inferred from crosssectional measures of the ventricles, the basal ganglia (caudate, putamen, pallidum, and nucleus accumbens), the thalamus, hippocampus and amygdala using magnetic resonance imaging data obtained from 18,605 individuals aged 3–90 years. All subcortical structure volumes were at their maximum value early in life. The volume of the basal ganglia showed a monotonic negative association with age thereafter; there was no significant association between age and the volumes of the thalamus, amygdala and the hippocampus (with some degree of decline in thalamus) until the sixth decade of life after which they also showed a steep negative association with age. The lateral ventricles showed continuous enlargement throughout the lifespan. Age was positively associated with inter-individual variability in the hippocampus and amygdala and the lateral ventricles. These results were robust to potential confounders and could be used to examine the functional significance of deviations from typical age-related morphometric patterns. KEYWORDS brain morphometry, ENIGMA, longitudinal trajectories, multisite DIMA ET AL.457 PI050427, PI020499; the Research Council, Grant/Award Number: 223273; South Eastern Norway Regional Health Authority, Grant/ Award Numbers: 2017-112, 2019107; Swedish Research Council; European Community's Seventh Framework Programme, Grant/Award Number: 602450; King's College London; South London and Maudsley NHS Foundation Trust; Biomedical Research Centre; National Institute for Health Research 1|INTRODUCTION Over the last 20 years, studies using structural magnetic resonance imaging (MRI) have confirmed that brain morphometric measures change with age. In general, whole brain, global and regional gray matter volumes increase during development and decrease with aging (Brain Development Cooperative Group, 2012; Driscoll et al., 2009; Fotenos, Snyder, Girton, Morris, & Buckner, 2005; Good et al., 2001; Pfefferbaum et al., 2013; Pomponio et al., 2019; Raz et al., 2005; Raznahan et al., 2014; Resnick, Pham, Kraut, Zonderman, & Davatzikos, 2003; Walhovd et al., 2011). However, most published studies are constrained by small sample sizes, restricted age coverage and methodological variability. These limitations introduce inconsistencies and may obscure or distort the lifespan trajectories of brain structures. To address these limitations, we formed the Lifespan Working group of the Enhancing Neuroimaging Genetics through Meta-Analysis (ENIGMA) Consortium (Thompson et al., 2014, 2017) to perform large-scale analyses of brain morphometric data extracted from MRI images using standardized protocols and unified quality control procedures, harmonized and validated across all participating sites. Here we focus on ventricular, striatal (caudate, putamen, nucleus accumbens), pallidal, thalamic, hippocampal and amygdala volumes. Subcortical structures are crucial for normal cognitive and emotional adaptation (Grossberg, 2009). The striatum and pallidum (together referred to as basal ganglia) are best known for their role in action selection and movement coordination (Calabresi, Picconi, Tozzi, Ghiglieri, & Di Filippo, 2014) but they are also involved in other aspects of cognition particularly memory, inhibitory control, reward and salience processing (Chudasama & Robbins, 2006; Richard, Castro, Difeliceantonio, Robinson, & Berridge, 2013; Scimeca & Badre, 2012; Tremblay, Worbe, Thobois, Sgambato-Faure, & Féger, 2015). The role of the hippocampus has been most clearly defined in connection to declarative memory (Eichenbaum, 2004; Shohamy & Turk-Browne, 2013) while the amygdala has been historically linked to affect processing (Kober et al., 2008). The thalamus is centrally located in the brain and acts as a key hub for the integration of motor and sensory information with higher-order functions (Sherman, 2005; Zhang, Snyder, Shimony, Fox, & Raichle, 2010). The role of subcortical structures extends beyond normal cognition because changes in the volume of these regions have been reliably identified in developmental (Ecker, Bookheimer, & Murphy, 2015; Krain & Castellanos, 2006), psychiatric (Hibar et al., 2016; Kempton et al., 2011; Schmaal et al., 2016; van Erp et al., 2016) and degenerative disorders (Risacher et al., 2009). Using data from 18,605 individuals aged 3–90 years from the ENIGMA Lifespan working group we delineated the association between age and subcortical volumes from early to late life in order to (a) identify periods of volume change or stability, (b) provide normative, age-adjusted centile curves of subcortical volumes and (c) quantify inter-individual variability in subcortical volumes which is considered a major source of inter-study differences (Dickie et al., 2013; Raz, Ghisletta, Rodrigue, Kennedy, & Lindenberger, 2010). 2|MATERIALS AND METHODS 2.1 |Study samples The study data derive from 88 samples comprising 18,605 healthy participants, aged 3–90 years, with near equal representation of men and women (48% and 52%) (Table 1, Figure 1). At the time of scanning, participating individuals were screened to exclude the presence of mental disorders, cognitive impairment or significant medical morbidity. Details of the screening process and eligibility criteria for each research group are shown in Table S1). 2.2 |Neuroimaging Detailed information on scanner vendor, magnet strength and acquisition parameters for each sample are presented in Table S1. For each sample, the intracranial volume (ICV) and the volume of the basal ganglia (caudate, putamen, pallidum, nucleus accumbens), thalamus, hippocampus, amygdala and lateral ventricles were extracted using FreeSurfer (http://surfer.nmr.mgh.harvard.edu) from high-resolution T 1 -weighted MRI brain scans (Fischl, 2012; Fischl et al., 2002). Prior to data pooling, images were visually inspected at each site to exclude participants whose scans were improperly segmented. After merging the samples, only individuals with complete data were included outliers were identified and excluded using Mahalanobis distances. All analyses described below were repeated for ICV-unadjusted volumetric measures which yielded identical results and are only presented as a separate supplement. Approximately 20% of the samples had a multi-scanner design. During data harmonization the scanner was modeled as a site. In each 458 DIMA ET AL. TABLE 1 Characteristics of the included samples Sample Age, mean, years Age, SD, years Age range Sample size N Number of males Number of females ABIDE 17 7.8 6 56 534 439 95 ADHD NF 13 1 12 15 13 7 6 ADNI 76 5.1 60 90 150 70 80 ADNI2GO 73 6.1 56 89 133 55 78 AMC 23 3.4 17 32 92 60 32 Barcelona 1.5T 15 1.8 11 17 30 14 16 Barcelona 3T 15 2.1 11 17 44 24 20 Betula 61 12.9 25 81 234 104 130 BIG 1.5T 28 13.3 13 77 1,288 628 660 BIG 3T 24 7.9 18 69 1,276 540 736 BIL&GIN 27 7.8 18 57 444 217 227 Bonn 39 6.5 29 50 174 174 0 BRAINSCALE 10 1.4 9 15 270 125 145 BRCATLAS 38 15.8 18 80 153 77 76 CAMH 41 17.6 18 86 128 65 63 Cardiff 25 7.4 18 58 316 87 229 CEG 16 1.7 13 19 32 32 0 CIAM 27 5 19 40 30 16 14 CLING 25 5.3 18 58 320 131 189 CODE 40 13.3 20 64 74 31 43 COMPULS/TS Eurotrain 11 1 9 13 53 36 17 Dublin (1) 37 13 17 65 52 23 29 Dublin (2) 30 8.3 19 52 92 51 41 Edinburgh 24 2.9 19 31 55 35 20 ENIGMA-HIV 25 4.4 19 33 31 16 15 ENIGMA-OCD (AMC/Huyser) 14 2.6 9 17 23 9 14 ENIGMA-OCD (IDIBELL) 33 10.1 18 61 65 29 36 ENIGMA-OCD (Kyushu/Nakao) 39 12.5 22 63 40 15 25 ENIGMA-OCD (London Cohort/MataixCols) 37 11.2 21 63 32 11 21 ENIGMA-OCD (van den Heuvel 1.5T) 31 7.6 21 53 48 18 30 ENIGMA-OCD (van den Heuvel 3T) 39 11.2 22 64 35 16 19 ENIGMA-OCD-3T-CONTROLS 31 10.6 19 56 27 10 17 FBIRN 37 11.2 19 60 173 123 50 FIDMAG 38 10.2 19 64 122 53 69 GSP 26 14.9 18 89 1962 860 1,102 HMS 40 12.2 19 64 55 21 34 HUBIN 42 8.9 19 56 99 66 33 IDIVAL (1) 65 10.2 49 87 31 10 21 IDIVAL (3) 30 7.7 19 50 114 69 45 IDIVAL(2) 28 7.6 15 52 79 49 30 IMAGEN 14 0.4 13 16 1744 864 880 IMH 32 10 20 59 79 50 29 IMpACT-NL 37 12 19 63 134 52 82 Indiana 1.5T 60 11 37 79 41 7 34 Indiana 3T 27 18.8 6 73 197 95 102 (Continues) DIMA ET AL.459 TABLE 1 (Continued) Sample Age, mean, years Age, SD, years Age range Sample size N Number of males Number of females Johns Hopkins 44 12.5 20 65 87 41 46 KaSP 27 5.7 20 43 32 15 17 Leiden 17 4.8 8 29 565 274 291 MAS 78 4.5 70 89 361 137 224 MCIC 33 12 18 60 93 63 30 Melbourne 20 3 15 26 102 54 48 METHCT 27 7.3 18 53 62 48 14 MHRC 22 2.9 16 28 52 52 0 Moods 33 9.8 18 51 310 146 164 NCNG 50 16.7 19 79 311 92 219 NESDA 40 9.8 21 56 65 22 43 NeuroIMAGE 17 3.7 8 29 376 172 204 Neuroventure 14 0.6 12 15 137 62 75 NTR (1) 15 1.4 11 18 34 11 23 NTR (2) 34 10.3 19 57 105 39 66 NTR (3) 30 5.9 20 42 29 11 18 NU 41 18.8 17 68 15 1 14 NUIG 37 11.5 18 58 89 50 39 NYU 31 8.7 19 52 51 31 20 OATS (1) 71 5.3 65 84 94 27 67 OATS (2) 68 4.4 65 81 33 13 20 OATS (3) 69 4.3 65 81 128 44 84 OATS (4) 70 4.6 65 89 95 23 72 OLIN 36 12.8 21 87 594 236 358 Oxford 16 1.4 14 19 38 18 20 PING 12 4.9 3 21 518 271 247 QTIM 23 3.4 16 30 342 112 230 Sao Paolo 1 27 5.8 17 43 69 45 24 Sao Paolo 3 30 8.1 18 50 83 44 39 SCORE 25 4.3 19 39 44 17 27 SHIP 2 55 12.3 31 84 368 206 162 SHIP TREND 50 13.9 21 81 788 439 349 StagedDep 47 8 27 59 84 20 64 Stanford 37 10.7 19 61 54 20 34 STROKEMRI 42 21.3 18 77 47 17 30 Sydney 37 21.1 12 79 147 58 89 TOP 35 9.8 18 73 296 155 141 Tuebingen 40 12.1 24 61 53 24 29 UMC Utrecht 1.5T 32 12.1 17 66 289 171 118 UMCU 3T 45 15.2 19 81 109 52 57 UNIBA 27 8.7 18 63 130 66 64 UPENN 36 13.6 16 85 185 85 100 Yale 14 2.2 10 18 23 12 11 Total 31 18.4 3 90 18,605 8,980 9,625 460 DIMA ET AL. T. Westlye (grant no. 2014-097) and STROKEMRI (grant no. 2013-054). HUBIN sample: HUBIN was supported by the Swedish Research Council (K2007-62X-15077-04-1, K2008-62P-20597-01-3, K2010-62X-15078-07-2, K2012-61X-15078-09-3), the regional agreement on medical training and clinical research between Stockholm County Council, and the Karolinska Institutet, and the Knut and Alice Wallenberg Foundation. The BIG database: this was established in Nijmegen in 2007, is now part of Cognomics, a joint initiative by researchers of the Donders Centre for Cognitive Neuroimaging, the Human Genetics and Cognitive Neuroscience departments of the Radboud university medical centre, and the Max Planck Institute for Psycholinguistics. The Cognomics Initiative is supported by the participating departments and centres and by external grants, including grants from the Biobanking and Biomolecular Resources Research Infrastructure (Netherlands) (BBMRI-NL) and the Hersenstichting Nederland. The authors also acknowledge grants supporting their work from the Netherlands Organization for Scientific Research (NWO), that is, the NWO Brain & Cognition Excellence Program (grant 433-09-229), the Vici Innovation Program (grant 016-130-669 to BF) and #91619115. Additional support is received from the European Community's Seventh Framework Programme (FP7/2007–2013) under grant agreements n 602805 (Aggressotype), n603016 (MATRICS), n602450 (IMAGEMEND), and n278948 (TACTICS), and from the European Community's Horizon 2020 Programme (H2020/2014–2020) under grant agreements n643051 (MiND) and n667302 (CoCA). CONFLICT OF INTEREST H.-J. G.: Travel grants and speaker honoraria from Fresenius Medical Care, Neuraxpharm, Servier and Janssen Cilag; research funding from Fresenius Medical Care. O. A. A.: Consultant to HealthLytix, speaker honorarium from Lundbeck. A. M. D.: Founder and member of the Scientific Advisory Board CorTechs Labs, Inc where he holds equity; member of the Scientific Advisory of Human Longevity Inc; research grants with General Electric Healthcare. DATA AVAILABILITY STATEMENT The ENIGMA Lifespan Working Group welcomes expression of interest from researchers in the field who wish to use the ENIGMA samples. Data sharing is possible subsequent to consent for the principal investigators of the contributing datasets. Requests should be directed to the corresponding authors. ORCID Danai Dima https://orcid.org/0000-0002-2598-0952 Gaelle E. Doucet https://orcid.org/0000-0003-4120-0474 Moji Aghajani https://orcid.org/0000-0003-2040-4881 Rachel M. Brouwer https://orcid.org/0000-0002-7466-1544 Christopher R. K. Ching https://orcid.org/0000-0003-2921-3408 Simon E. Fisher https://orcid.org/0000-0002-3132-1996 Thomas Frodl https://orcid.org/0000-0002-8113-6959 David C. Glahn https://orcid.org/0000-0002-4749-6977 Ian H. 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Z., Shimony, J. S., Fox, M. D., & Raichle, M. E. (2010). Noninvasive functional and structural connectivity mapping of the human thalamocortical system. Cerebral Cortex,20, 1187–1194. SUPPORTING INFORMATION Additional supporting information may be found online in the Supporting Information section at the end of this article. How to cite this article: Dima D, Modabbernia A, Papachristou E, et al. Subcortical volumes across the lifespan: Data from 18,605 healthy individuals aged 3–90 years. Hum Brain Mapp. 2022;43:452–469. https://doi.org/10.1002/hbm. 25320 DIMA ET AL.469