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Greater male than female variability in regional brain structure across the lifespan

View ORCID ProfileLara M Wierenga, View ORCID ProfileGaelle E Doucet, Danai Dima, View ORCID ProfileIngrid Agartz, Moji Aghajani, Theophilus N Akudjedu, Anton Albajes-Eizagirre, View ORCID ProfileDag Alnæs, Kathryn I Alpert, Ole A Andreassen, Alan Anticevic, Philip Asherson, Tobias Banaschewski, View ORCID ProfileNuria Bargallo, Sarah Baumeister, Ramona Baur-Streubel, Alessandro Bertolino, Aurora Bonvino, View ORCID ProfileDorret I Boomsma, Stefan Borgwardt, Josiane Bourque, Anouk den Braber, Daniel Brandeis, Alan Breier, Henry Brodaty, Rachel M Brouwer, View ORCID ProfileJan K Buitelaar, Geraldo F Busatto, Vince D Calhoun, Erick J Canales-Rodríguez, Dara M Cannon, Xavier Caseras, View ORCID ProfileFrancisco X Castellanos, View ORCID ProfileTiffany M Chaim-Avancini, Christopher RK Ching, View ORCID ProfileVincent P Clark, Patricia J Conrod, Annette Conzelmann, Fabrice Crivello, Christopher G Davey, Erin W Dickie, Stefan Ehrlich, Dennis van ’t Ent, View ORCID ProfileSimon E Fisher, Jean-Paul Fouche, View ORCID ProfileBarbara Franke, Paola Fuentes-Claramonte, Eco JC de Geus, Annabella Di Giorgio, David C Glahn, Ian H Gotlib, View ORCID ProfileHans J Grabe, Oliver Gruber, Patricia Gruner, Raquel E Gur, Ruben C Gur, View ORCID ProfileTiril P Gurholt, Lieuwe de Haan, Beathe Haatveit, Ben J Harrison, View ORCID ProfileCatharina A Hartman, View ORCID ProfileSean N Hatton, Dirk J Heslenfeld, Odile A van den Heuvel, Ian B Hickie, View ORCID ProfilePieter J Hoekstra, Sarah Hohmann, View ORCID ProfileAvram J Holmes, Martine Hoogman, Norbert Hosten, Fleur M Howells, Hilleke E Hulshoff Pol, Chaim Huyser, Neda Jahanshad, Anthony C James, Jiyang Jiang, Erik G Jönsson, John A Joska, View ORCID ProfileAndrew J Kalnin, Karolinska Schizophrenia Project (KaSP) Consortium, Marieke Klein, Laura Koenders, Knut K Kolskår, Bernd Krämer, Jonna Kuntsi, Jim Lagopoulos, Luisa Lazaro, Irina S Lebedeva, Phil H Lee, Christine Lochner, Marise WJ Machielsen, Sophie Maingault, Nicholas G Martin, Ignacio Martínez-Zalacaín, David Mataix-Cols, Bernard Mazoyer, Brenna C McDonald, Colm McDonald, View ORCID ProfileAndrew M McIntosh, Katie L McMahon, Genevieve McPhilemy, Dennis van der Meer, José M Menchón, Jilly Naaijen, Lars Nyberg, View ORCID ProfileJaap Oosterlaan, View ORCID ProfileYannis Paloyelis, Paul Pauli, Giulio Pergola, Edith Pomarol-Clotet, Maria J Portella, Joaquim Radua, Andreas Reif, View ORCID ProfileGeneviève Richard, Joshua L Roffman, Pedro GP Rosa, Matthew D Sacchet, View ORCID ProfilePerminder S Sachdev, Raymond Salvador, Salvador Sarró, Theodore D Satterthwaite, View ORCID ProfileAndrew J Saykin, Mauricio H Serpa, Kang Sim, Andrew Simmons, Jordan W Smoller, Iris E Sommer, Carles Soriano-Mas, Dan J Stein, Lachlan T Strike, Philip R Szeszko, Henk S Temmingh, Sophia I Thomopoulos, Alexander S Tomyshev, Julian N Trollor, Anne Uhlmann, Ilya M Veer, Dick J Veltman, Aristotle Voineskos, Henry Völzke, Henrik Walter, Lei Wang, View ORCID ProfileYang Wang, View ORCID ProfileBernd Weber, Wei Wen, John D West, View ORCID ProfileLars T Westlye, Heather C Whalley, Steven CR Williams, Katharina Wittfeld, Daniel H Wolf, Margaret J Wright, Yuliya N Yoncheva, Marcus V Zanetti, Georg C Ziegler, Greig I de Zubicaray, Paul M Thompson, Eveline A Crone, Sophia Frangou, Christian K Tamnes
doi: https://doi.org/10.1101/2020.02.17.952010
Lara M Wierenga
1Leiden University, Leiden, the Netherlands
2Leiden Institute for Brain and Cognition, Leiden, the Netherlands
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  • ORCID record for Lara M Wierenga
  • For correspondence: l.m.wierenga@fsw.leidenuniv.nl
Gaelle E Doucet
3Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, USA
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  • ORCID record for Gaelle E Doucet
Danai Dima
4Department of Psychology, School of Arts and Social Sciences, City, University of London, London, UK
5Department of Neuroimaging, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, London, UK
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Ingrid Agartz
6Norwegian Centre for Mental Disorders Research (NORMENT), Division of Mental Health and Addiction, Institute of Clinical Medicine, University of Oslo, Oslo, Norway
7Department of Psychiatric Research, Diakonhjemmet Hospital, Oslo, Norway
8Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet, & Stockholm Health Care Services, Stockholm County Council, Stockholm, Sweden
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Moji Aghajani
9Department of Psychiatry, Amsterdam Neuroscience, Amsterdam UMC, Vrije Universiteit, Amsterdam, the Netherlands
10GGZ inGeest, Department of Research & Innovation, Amsterdam, The Netherlands
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Theophilus N Akudjedu
11Centre for Neuroimaging & Cognitive Genomics (NICOG), Clinical Neuroimaging Laboratory, NCBES Galway Neuroscience Centre, College of Medicine Nursing and Health Sciences, National University of Ireland Galway, Galway, Ireland
12Institute of Medical Imaging & Visualisation, Faculty of Health & Social Sciences, Bournemouth University, Bournemouth, UK
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Anton Albajes-Eizagirre
13FIDMAG Germanes Hospitalàries Research Foundation, Barcelona, Spain
14Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Madrid, Spain
15Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
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Dag Alnæs
6Norwegian Centre for Mental Disorders Research (NORMENT), Division of Mental Health and Addiction, Institute of Clinical Medicine, University of Oslo, Oslo, Norway
16Norwegian Centre for Mental Disorders Research (NORMENT), Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway
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Kathryn I Alpert
17Department of Psychiatry and Behavioral Sciences, Northwestern University Feinberg School of Medicine, Chicago, USA
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Ole A Andreassen
6Norwegian Centre for Mental Disorders Research (NORMENT), Division of Mental Health and Addiction, Institute of Clinical Medicine, University of Oslo, Oslo, Norway
16Norwegian Centre for Mental Disorders Research (NORMENT), Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway
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Alan Anticevic
18Department of Psychiatry, Yale University, New Haven, USA
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Philip Asherson
19Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, London, UK
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Tobias Banaschewski
20Department of Child and Adolescent Psychiatry and Psychotherapy, Central Institute of Mental Health, University of Heidelberg, Medical Faculty Mannheim, Mannheim, Germany
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Nuria Bargallo
21Imaging Diagnostic Center, Hospital Clínic, Barcelona, Spain
22Magnetic Resonance Image Core Facility, IDIBAPS, Barcelona, Spain
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Sarah Baumeister
20Department of Child and Adolescent Psychiatry and Psychotherapy, Central Institute of Mental Health, University of Heidelberg, Medical Faculty Mannheim, Mannheim, Germany
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Ramona Baur-Streubel
23Department for Clinical Psychology, Würzburg University, Margetshöchheim, Germany
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Alessandro Bertolino
24Department of Basic Medical Science, Neuroscience and Sense Organs, University of Bari Aldo Moro, Bari, Italy
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Aurora Bonvino
25University of Bari Aldo Moro, Bari, Italy
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Dorret I Boomsma
26Department of Biological Psychology, VU University Amsterdam, Amsterdam, the Netherlands
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Stefan Borgwardt
27Department of Psychiatry, University of Basel, Basel, Switzerland
28Department of Psychiatry, University of Lübeck, Lübeck, Germany
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Josiane Bourque
29Department of Psychiatry, University of Pennsylvania, Philadelphia, USA
30CHU Sainte-Justine Research Center, Montreal, Quebec, Canada
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Anouk den Braber
26Department of Biological Psychology, VU University Amsterdam, Amsterdam, the Netherlands
31Alzheimer Center, Amsterdam UMC, Location VUMC, Amsterdam, the Netherlands
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Daniel Brandeis
20Department of Child and Adolescent Psychiatry and Psychotherapy, Central Institute of Mental Health, University of Heidelberg, Medical Faculty Mannheim, Mannheim, Germany
32Department of Child and Adolescent Psychiatry and Psychotherapy, Psychiatric Hospital, University of Zurich, Zurich, Switzerland
33Zurich Center for Integrative Human Physiology, University of Zurich, Zurich, Switzerland
34Neuroscience Centre Zurich, University and ETH Zurich, Zurich, Switzerland
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Alan Breier
35Department of Psychiatry, Indiana University School of Medicine, Indianapolis, USA
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Henry Brodaty
36Centre for Healthy Brain Ageing, School of Psychiatry, University of New South Wales, Sydney, Australia
37Dementia Centre for Research Collaboration, School of Psychiatry, University of New South Wales, Sydney, Australia
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Rachel M Brouwer
38Department of Psychiatry, University Medical Center Utrecht Brain Center, Utrecht University, Utrecht, the Netherlands
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Jan K Buitelaar
39Department of Cognitive Neuroscience, Radboud University Medical Centre, Nijmegen, the Netherlands
40Karakter Child and Adolescent Psychiatry University Centre, Nijmegen, the Netherlands
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Geraldo F Busatto
41Laboratory of Psychiatric Neuroimaging (LIM-21), Departamento e Instituto de Psiquiatria, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil
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Vince D Calhoun
42Tri-institutional Center for Translational Research in Neuroimaging and Data Science (TReNDS), Georgia State, Georgia Tech, Emory, Atlanta, USA
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Erick J Canales-Rodríguez
13FIDMAG Germanes Hospitalàries Research Foundation, Barcelona, Spain
14Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Madrid, Spain
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Dara M Cannon
11Centre for Neuroimaging & Cognitive Genomics (NICOG), Clinical Neuroimaging Laboratory, NCBES Galway Neuroscience Centre, College of Medicine Nursing and Health Sciences, National University of Ireland Galway, Galway, Ireland
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Xavier Caseras
43MRC Centre for Neuropsychiatric Genetics and Genomics, Cardiff University, Cardiff, UK
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Francisco X Castellanos
44Department of Child and Adolescent Psychiatry, NYU Grossman School of Medicine, New York, USA
45Nathan Kline Institute for Psychiatric Research, Orangeburg, NY, USA
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Tiffany M Chaim-Avancini
41Laboratory of Psychiatric Neuroimaging (LIM-21), Departamento e Instituto de Psiquiatria, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil
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Christopher RK Ching
46Imaging Genetics Center, Mark and Mary Stevens Neuroimaging and Informatics Institute, Keck School of Medicine, University of Southern California, Marina del Rey, USA
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Vincent P Clark
47Psychology Clinical Neuroscience Center, Department of Psychology, University of New Mexico, Albuquerque, NM, USA
48Mind Research Network, Albuquerque, NM, USA
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Patricia J Conrod
30CHU Sainte-Justine Research Center, Montreal, Quebec, Canada
49Department of Psychiatry, University of Montreal, Montreal, Canada
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Annette Conzelmann
50Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, University of Tübingen, Tübingen, Germany
51PFH – Private University of Applied Sciences, Department of Psychology (Clinical Psychology II), Göttingen, Germany
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Fabrice Crivello
52Groupe d’Imagerie Neurofonctionnelle, Institut des Maladies Neurodégénératives, Bordeaux, France
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Christopher G Davey
53Centre for Youth Mental Health, University of Melbourne, Parkville, Australia
54Orygen, Parkville, Victoria, Australia
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Erin W Dickie
55Campbell Family Mental Health Institute, Centre for Addiction and Mental Health, Department of Psychiatry, University of Toronto, Toronto, Canada
56Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada
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Stefan Ehrlich
57Division of Psychological & Social Medicine and Developmental Neurosciences; Technische Universität Dresden, Faculty of Medicine, University Hospital C.G. Carus, TU-Dresden, Dresden, Germany
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Dennis van ’t Ent
26Department of Biological Psychology, VU University Amsterdam, Amsterdam, the Netherlands
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Simon E Fisher
58Language and Genetics Department, Max Planck Institute for Psycholinguistics, Nijmegen, the Netherlands
59Donders Institute for Brain, Cognition and Behaviour, Radboud University, Nijmegen, the Netherlands
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Jean-Paul Fouche
60Department of Psychiatry and Neuroscience Institute, University of Cape Town, Cape Town, Western Cape, South Africa
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Barbara Franke
59Donders Institute for Brain, Cognition and Behaviour, Radboud University, Nijmegen, the Netherlands
61Department of Human Genetics, Radboud University Medical Center, Nijmegen, the Netherlands
62Department of Psychiatry, Radboud University Medical Center, Nijmegen, the Netherlands
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Paola Fuentes-Claramonte
13FIDMAG Germanes Hospitalàries Research Foundation, Barcelona, Spain
14Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Madrid, Spain
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Eco JC de Geus
26Department of Biological Psychology, VU University Amsterdam, Amsterdam, the Netherlands
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Annabella Di Giorgio
63IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy
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David C Glahn
64Tommy Fuss Center for Neuropsychiatric Disease Research, Department of Psychiatry, Boston Children’s Hospital and Harvard Medical School, Boston, USA
65Olin Center for Neuropsychiatric Research, Institute of Living, Hartford Hospital, Hartford, CT, USA
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Ian H Gotlib
66Department of Psychology, Stanford University, Stanford, USA
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Hans J Grabe
67Department of Psychiatry and Psychotherapy, University Medicine Greifswald, Greifswald, Germany
68German Center for Neurodegenerative Diseases (DZNE), Site Rostock/Greifswald, Greifswald, Germany
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Oliver Gruber
69Section for Experimental Psychopathology and Neuroimaging, Department of General Psychiatry, Heidelberg University Hospital, Heidelberg, Germany
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Patricia Gruner
18Department of Psychiatry, Yale University, New Haven, USA
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Raquel E Gur
29Department of Psychiatry, University of Pennsylvania, Philadelphia, USA
70Lifespan Brain Institute, Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania, USA
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Ruben C Gur
29Department of Psychiatry, University of Pennsylvania, Philadelphia, USA
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Tiril P Gurholt
6Norwegian Centre for Mental Disorders Research (NORMENT), Division of Mental Health and Addiction, Institute of Clinical Medicine, University of Oslo, Oslo, Norway
16Norwegian Centre for Mental Disorders Research (NORMENT), Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway
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Lieuwe de Haan
71Department of Early Psychosis, Amsterdam UMC, Amsterdam, the Netherlands
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Beathe Haatveit
6Norwegian Centre for Mental Disorders Research (NORMENT), Division of Mental Health and Addiction, Institute of Clinical Medicine, University of Oslo, Oslo, Norway
16Norwegian Centre for Mental Disorders Research (NORMENT), Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway
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Ben J Harrison
72Melbourne Neuropsychiatry Centre, Department of Psychiatry, The University of Melbourne & Melbourne Health, Melbourne, Australia
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Catharina A Hartman
73Interdisciplinary Center Psychopathology and Emotion regulation, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
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Sean N Hatton
74Brain and Mind Centre, University of Sydney, Sydney, Australia
75Department of Neurosciences, University of California San Diego, La Jolla, CA, USA
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Dirk J Heslenfeld
76Departments of Experimental and Clinical Psychology, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands
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Odile A van den Heuvel
9Department of Psychiatry, Amsterdam Neuroscience, Amsterdam UMC, Vrije Universiteit, Amsterdam, the Netherlands
77Department of Anatomy & Neurosciences, Amsterdam Neuroscience, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands
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Ian B Hickie
74Brain and Mind Centre, University of Sydney, Sydney, Australia
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Pieter J Hoekstra
78Department of Psychiatry, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
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Sarah Hohmann
20Department of Child and Adolescent Psychiatry and Psychotherapy, Central Institute of Mental Health, University of Heidelberg, Medical Faculty Mannheim, Mannheim, Germany
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Avram J Holmes
18Department of Psychiatry, Yale University, New Haven, USA
79Department of Psychology, Yale University, New Haven, USA
80Department of Psychiatry, Massachusetts General Hospital, Boston, MA, USA
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Martine Hoogman
59Donders Institute for Brain, Cognition and Behaviour, Radboud University, Nijmegen, the Netherlands
61Department of Human Genetics, Radboud University Medical Center, Nijmegen, the Netherlands
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Norbert Hosten
81Institute of Diagnostic Radiology and Neuroradiology, University Medicine Greifswald, Greifswald, Germany
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Fleur M Howells
82Neuroscience Institute, University of Cape Town, Cape Town, Western Cape, South Africa
83Department of Psychiatry and Mental Health, University of Cape Town, Cape Town, Western Cape, South Africa
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Hilleke E Hulshoff Pol
38Department of Psychiatry, University Medical Center Utrecht Brain Center, Utrecht University, Utrecht, the Netherlands
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Chaim Huyser
84De Bascule, Academic center child and adolescent psychiatry, Duivendrecht, the Netherlands
85Amsterdam UMC department of child and adolescent psychiatry, Amsterdam, the Netherlands
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Neda Jahanshad
46Imaging Genetics Center, Mark and Mary Stevens Neuroimaging and Informatics Institute, Keck School of Medicine, University of Southern California, Marina del Rey, USA
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Anthony C James
86Department of Psychiatry, Warneford Hospital, Oxford, UK
87Highfield Unit, Warneford Hospital, Oxford, UK
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Jiyang Jiang
36Centre for Healthy Brain Ageing, School of Psychiatry, University of New South Wales, Sydney, Australia
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Erik G Jönsson
6Norwegian Centre for Mental Disorders Research (NORMENT), Division of Mental Health and Addiction, Institute of Clinical Medicine, University of Oslo, Oslo, Norway
8Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet, & Stockholm Health Care Services, Stockholm County Council, Stockholm, Sweden
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John A Joska
83Department of Psychiatry and Mental Health, University of Cape Town, Cape Town, Western Cape, South Africa
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Andrew J Kalnin
88Department of Radiology, The Ohio State University College of Medicine, Columbus, Ohio, USA
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89Members of Karolinska Schizophrenia Project (KaSP) Consortium are listed at the end of the manuscript as collaborators
Marieke Klein
38Department of Psychiatry, University Medical Center Utrecht Brain Center, Utrecht University, Utrecht, the Netherlands
59Donders Institute for Brain, Cognition and Behaviour, Radboud University, Nijmegen, the Netherlands
61Department of Human Genetics, Radboud University Medical Center, Nijmegen, the Netherlands
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Laura Koenders
71Department of Early Psychosis, Amsterdam UMC, Amsterdam, the Netherlands
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Knut K Kolskår
16Norwegian Centre for Mental Disorders Research (NORMENT), Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway
90Department of Psychology, University of Oslo, Oslo, Norway
91Sunnaas Rehabilitation Hospital HT, Nesodden, Norway
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Bernd Krämer
69Section for Experimental Psychopathology and Neuroimaging, Department of General Psychiatry, Heidelberg University Hospital, Heidelberg, Germany
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Jonna Kuntsi
19Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, London, UK
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Jim Lagopoulos
92Sunshine Coast Mind and Neuroscience Thompson Institute, Birtinya, Australia
93University of the Sunshine Coast, Australia
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Luisa Lazaro
14Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Madrid, Spain
94Department of Child and Adolescent Psychiatry and Psychology, Hospital Clínic, Barcelona, Spain, Barcelona, Spain
95August Pi i Sunyer Biomedical Research Institut (IDIBAPS), Barcelona, Spain
96Department of Medicine, University of Barcelona, Barcelona, Spain
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Irina S Lebedeva
97Laboratory of Neuroimaging and Multimodal Analysis, Mental Health Research Center, Moscow, Russia
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98Department of Psychiatry, Massachusetts General Hospital, Boston, USA
99Department of Psychiatry, Harvard Medical School, Boston, MA, USA
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Christine Lochner
100SA MRC Unit on Risk and Resilience in Mental Disorders, Department of Psychiatry, Stellenbosch University, Cape Town, Western Cape, South Africa
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101Department of Psychiatry, Academic Medical Center, Amsterdam, the Netherlands
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102Institut des maladies neurodégénératives, Université de Bordeaux, Bordeaux, France
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103Genetic Epidemiology, QIMR Berghofer Medical Research Institute, Brisbane, Australia
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104Department of Psychiatry, Bellvitge University Hospital, Bellvitge Biomedical Research Institute-IDIBELL, Barcelona, Spain
105Department of Clinical Sciences, University of Barcelona, Barcelona, Spain
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8Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet, & Stockholm Health Care Services, Stockholm County Council, Stockholm, Sweden
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106University of Bordeaux, Bordeaux, France
107Bordeaux University Hospital, Bordeaux, France
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108Department of Radiology and Imaging Sciences, Indiana University School of Medicine, Indianapolis, USA
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11Centre for Neuroimaging & Cognitive Genomics (NICOG), Clinical Neuroimaging Laboratory, NCBES Galway Neuroscience Centre, College of Medicine Nursing and Health Sciences, National University of Ireland Galway, Galway, Ireland
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109Division of Psychiatry, University of Edinburgh, Edinburgh, UK
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110Herston Imaging Research Facility and School of Clinical Sciences, Queensland University of Technology (QUT), Brisbane, Australia
111Faculty of Health, Institute of Health and Biomedical Innovation, Queensland University of Technology (QUT), Brisbane, Australia
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6Norwegian Centre for Mental Disorders Research (NORMENT), Division of Mental Health and Addiction, Institute of Clinical Medicine, University of Oslo, Oslo, Norway
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112School of Mental Health and Neuroscience, Faculty of Health, Medicine and Life Sciences, Maastricht University, Maastricht, the Netherlands
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14Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Madrid, Spain
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105Department of Clinical Sciences, University of Barcelona, Barcelona, Spain
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39Department of Cognitive Neuroscience, Radboud University Medical Centre, Nijmegen, the Netherlands
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113Department of Radiation Sciences, Umeå University, Umeå, Sweden
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115Emma Children’s Hospital, Amsterdam UMC University of Amsterdam and Vrije Universiteit Amsterdam, Emma Neuroscience Group, Department of Pediatrics, Amsterdam Reproduction & Development, Amsterdam, the Netherlands
116Clinical Neuropsychology Section, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands
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5Department of Neuroimaging, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, London, UK
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117Department of Psychology, University of Würzburg, Würzburg, Germany
118Centre of Mental Health, Medical Faculty, University of Würzburg, Würzburg, Germany
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24Department of Basic Medical Science, Neuroscience and Sense Organs, University of Bari Aldo Moro, Bari, Italy
119Lieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, MD, USA
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13FIDMAG Germanes Hospitalàries Research Foundation, Barcelona, Spain
14Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Madrid, Spain
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14Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Madrid, Spain
120Department of Psychiatry, Institut d’Investigació Biomèdica Sant Pau, Barcelona, Spain
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8Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet, & Stockholm Health Care Services, Stockholm County Council, Stockholm, Sweden
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14Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Madrid, Spain
15Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
121Early Psychosis: Interventions and Clinical-detection (EPIC) lab, Department of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, London, UK
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122Department of Psychiatry, Psychosomatic Medicine and Psychotherapy, University Hospital Frankfurt, Frankfurt Am Main, Germany
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6Norwegian Centre for Mental Disorders Research (NORMENT), Division of Mental Health and Addiction, Institute of Clinical Medicine, University of Oslo, Oslo, Norway
16Norwegian Centre for Mental Disorders Research (NORMENT), Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway
90Department of Psychology, University of Oslo, Oslo, Norway
91Sunnaas Rehabilitation Hospital HT, Nesodden, Norway
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123Department of Psychiatry, Massachusetts General Hospital and Harvard Medical School, Charlestown, USA
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Pedro GP Rosa
41Laboratory of Psychiatric Neuroimaging (LIM-21), Departamento e Instituto de Psiquiatria, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil
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124Center for Depression, Anxiety, and Stress Research, McLean Hospital, Harvard Medical School, Belmont, USA
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36Centre for Healthy Brain Ageing, School of Psychiatry, University of New South Wales, Sydney, Australia
125Neuropsychiatric Institute, The Prince of Wales Hospital, Randwick, NSW, Australia
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Raymond Salvador
13FIDMAG Germanes Hospitalàries Research Foundation, Barcelona, Spain
14Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Madrid, Spain
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Salvador Sarró
13FIDMAG Germanes Hospitalàries Research Foundation, Barcelona, Spain
14Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Madrid, Spain
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Theodore D Satterthwaite
126Department of Psychiatry, University of Pennsylvania, Philadelphia, USA
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108Department of Radiology and Imaging Sciences, Indiana University School of Medicine, Indianapolis, USA
127Indiana Alzheimer Disease Center, Indianapolis, Indiana, USA
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Mauricio H Serpa
41Laboratory of Psychiatric Neuroimaging (LIM-21), Departamento e Instituto de Psiquiatria, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil
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Kang Sim
128West Region, Institute of Mental Health, Singapore, Singapore
129Yong Loo Lin School of Medicine, National University of Singapore, Singapore
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Andrew Simmons
130Department of Neuroimaging, Institute of Psychiatry, Psychology and Neurology, King’s College London, London, UK
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Jordan W Smoller
98Department of Psychiatry, Massachusetts General Hospital, Boston, USA
131Psychiatric and Neurodevelopmental Genetics Unit, Center for Genomic Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA
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Iris E Sommer
132Department of Biomedical Sciences of Cells and Systems, Rijksuniversiteit Groningen, University Medical Center Groningen, Groningen, the Netherlands
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Carles Soriano-Mas
14Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Madrid, Spain
104Department of Psychiatry, Bellvitge University Hospital, Bellvitge Biomedical Research Institute-IDIBELL, Barcelona, Spain
133Department of Psychobiology and Methodology in Health Sciences, Universitat Autònoma de Barcelona, Barcelona, Spain
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Dan J Stein
134SAMRC Unit on Risk & Resilience in Mental Disorders, Dept of Psychiatry & Neuroscience Institute, University of Cape Town, Cape Town, Western Cape, South Africa
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Lachlan T Strike
135Queensland Brain Institute, University of Queensland, Brisbane, Australia
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Philip R Szeszko
136Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, USA
137Mental Illness Research, Education and Clinical Center (MIRECC), James J. Peters VA Medical Center, Bronx, New York, USA
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Henk S Temmingh
83Department of Psychiatry and Mental Health, University of Cape Town, Cape Town, Western Cape, South Africa
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46Imaging Genetics Center, Mark and Mary Stevens Neuroimaging and Informatics Institute, Keck School of Medicine, University of Southern California, Marina del Rey, USA
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Alexander S Tomyshev
97Laboratory of Neuroimaging and Multimodal Analysis, Mental Health Research Center, Moscow, Russia
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36Centre for Healthy Brain Ageing, School of Psychiatry, University of New South Wales, Sydney, Australia
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Anne Uhlmann
83Department of Psychiatry and Mental Health, University of Cape Town, Cape Town, Western Cape, South Africa
138Department of Child and Adolescent Psychiatry and Psychotherapy, Faculty of Medicine Carl Gustav Carus of TU Dresden, Dresden, Germany
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Ilya M Veer
139Department of Psychiatry and Psychotherapy CCM, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany
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Dick J Veltman
140Department of Psychiatry & Amsterdam Neuroscience, Amsterdam UMC, location VUMC, Amsterdam, the Netherlands
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Aristotle Voineskos
55Campbell Family Mental Health Institute, Centre for Addiction and Mental Health, Department of Psychiatry, University of Toronto, Toronto, Canada
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Henry Völzke
141Institute for Community Medicine, University Medicine Greifswald, Greifswald, Germany
142DZHK (German Centre for Cardiovascular Research), partner site Greifswald, Greifswald, Germany
143DZD (German Center for Diabetes Research), partner site Greifswald, Greifswald, Germany
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Henrik Walter
139Department of Psychiatry and Psychotherapy CCM, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany
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Lei Wang
17Department of Psychiatry and Behavioral Sciences, Northwestern University Feinberg School of Medicine, Chicago, USA
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Yang Wang
144Department of Radiology, Medical College of Wisconsin, Milwaukee, USA
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Bernd Weber
145Institute for Experimental Epileptology and Cognition Research, University Hospital Bonn, Bonn, Germany
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36Centre for Healthy Brain Ageing, School of Psychiatry, University of New South Wales, Sydney, Australia
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108Department of Radiology and Imaging Sciences, Indiana University School of Medicine, Indianapolis, USA
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6Norwegian Centre for Mental Disorders Research (NORMENT), Division of Mental Health and Addiction, Institute of Clinical Medicine, University of Oslo, Oslo, Norway
16Norwegian Centre for Mental Disorders Research (NORMENT), Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway
90Department of Psychology, University of Oslo, Oslo, Norway
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Heather C Whalley
109Division of Psychiatry, University of Edinburgh, Edinburgh, UK
146Division of Psychiatry, Royal Edinburgh Hospital, Edinburgh, UK
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147Department of Neuroimaging, King’s College London, London, UK
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67Department of Psychiatry and Psychotherapy, University Medicine Greifswald, Greifswald, Germany
68German Center for Neurodegenerative Diseases (DZNE), Site Rostock/Greifswald, Greifswald, Germany
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29Department of Psychiatry, University of Pennsylvania, Philadelphia, USA
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135Queensland Brain Institute, University of Queensland, Brisbane, Australia
148Centre for Advanced Imaging, University of Queensland, Brisbane, Queensland, Australia
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Yuliya N Yoncheva
149Department of Child and Adolescent Psychiatry, NYU Child Study Center, Hassenfeld Children’s Hospital at NYU Langone, New York, USA
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Marcus V Zanetti
41Laboratory of Psychiatric Neuroimaging (LIM-21), Departamento e Instituto de Psiquiatria, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil
150Instituto de Ensino e Pesquisa, Hospital Sírio-Libanês, São Paulo, Brazil
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Georg C Ziegler
151Division of Molecular Psychiatry, Center of Mental Health, University of Würzburg, Würzburg, Würzburg, Germany
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Greig I de Zubicaray
111Faculty of Health, Institute of Health and Biomedical Innovation, Queensland University of Technology (QUT), Brisbane, Australia
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Paul M Thompson
46Imaging Genetics Center, Mark and Mary Stevens Neuroimaging and Informatics Institute, Keck School of Medicine, University of Southern California, Marina del Rey, USA
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Eveline A Crone
1Leiden University, Leiden, the Netherlands
2Leiden Institute for Brain and Cognition, Leiden, the Netherlands
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Sophia Frangou
3Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, USA
152Centre for Brain Health, University of British Columbia, Vancouver, British Columbia, Canada
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Christian K Tamnes
6Norwegian Centre for Mental Disorders Research (NORMENT), Division of Mental Health and Addiction, Institute of Clinical Medicine, University of Oslo, Oslo, Norway
7Department of Psychiatric Research, Diakonhjemmet Hospital, Oslo, Norway
153PROMENTA Research Center, Department of Psychology, University of Oslo, Oslo, Norway
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Abstract

For many traits, males show greater variability than females, with possible implications for understanding sex differences in health and disease. Here, the ENIGMA (Enhancing Neuro Imaging Genetics through Meta-Analysis) Consortium presents the largest-ever mega-analysis of sex differences in variability of brain structure, based on international data spanning nine decades of life. Subcortical volumes, cortical surface area and cortical thickness were assessed in MRI data of 16,683 healthy individuals 1-90 years old (47% females). We observed significant patterns of greater male than female between-subject variance for all subcortical volumetric measures, all cortical surface area measures, and 60% of cortical thickness measures. This pattern was stable across the lifespan for 50% of the subcortical structures, 70% of the regional area measures, and nearly all regions for thickness. Our findings that these sex differences are present in childhood implicate early life genetic or gene-environment interaction mechanisms. The findings highlight the importance of individual differences within the sexes, that may underpin sex-specific vulnerability to disorders.

Competing Interest Statement

The authors declare the following competing interests: OAA: Speakers honorarium from Lundbeck, Consultant of HealthLyti; PA: Received payments for consultancy to Shire/Takeda, Medic, educational/research awards from Shire/Takeda, GW Pharma, Janssen-Cila, speaker at sponsored events for Shire, Flynn Pharma, Medic; TB: advisory or consultancy role for Lundbeck, Medice, Neurim Pharmaceuticals, Oberberg GmbH, Shire, and Infectopharm, conference support or speakers fee by Lilly, Medice, and Shire, received royalities from Hogrefe, Kohlhammer, CIP Medien, Oxford University Press - the present work is unrelated to the above grants and relationship; DB: serves as an unpaid scientific consultant for an EU-funded neurofeedback trial that is unrelated to the present work; HB: Advisory Board, Nutricia Australi; CRKC: received partial research support from Biogen, Inc. (Boston, USA) for work unrelated to the topic of this manuscript; BF: received educational speaking fees from Medice; HJG: received travel grants and speakers honoraria from Fresenius Medical Care, Neuraxpharm, Servier and Janssen Cilag as well as research funding from Fresenius Medical Care; NJ and PMT: MPI of a research related grant from Biogen, Inc., for research unrelated to the contents of this manuscript; JK: given talks at educational events sponsored by Medic; all funds are received by Kings College London and used for studies of ADHD; DM-C: receives fees from UpToDate, Inc and Elsevier, all unrelated to the current work; AMM: received research support from Eli Lilly, Janssen, and the Sackler Foundation, and speaker fees from Illumina and Janssen; DJS: received research grants and/or honoraria from Lundbeck and Sun. The remaining authors declare no competing interests.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-ND 4.0 International license.
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Greater male than female variability in regional brain structure across the lifespan
Lara M Wierenga, Gaelle E Doucet, Danai Dima, Ingrid Agartz, Moji Aghajani, Theophilus N Akudjedu, Anton Albajes-Eizagirre, Dag Alnæs, Kathryn I Alpert, Ole A Andreassen, Alan Anticevic, Philip Asherson, Tobias Banaschewski, Nuria Bargallo, Sarah Baumeister, Ramona Baur-Streubel, Alessandro Bertolino, Aurora Bonvino, Dorret I Boomsma, Stefan Borgwardt, Josiane Bourque, Anouk den Braber, Daniel Brandeis, Alan Breier, Henry Brodaty, Rachel M Brouwer, Jan K Buitelaar, Geraldo F Busatto, Vince D Calhoun, Erick J Canales-Rodríguez, Dara M Cannon, Xavier Caseras, Francisco X Castellanos, Tiffany M Chaim-Avancini, Christopher RK Ching, Vincent P Clark, Patricia J Conrod, Annette Conzelmann, Fabrice Crivello, Christopher G Davey, Erin W Dickie, Stefan Ehrlich, Dennis van ’t Ent, Simon E Fisher, Jean-Paul Fouche, Barbara Franke, Paola Fuentes-Claramonte, Eco JC de Geus, Annabella Di Giorgio, David C Glahn, Ian H Gotlib, Hans J Grabe, Oliver Gruber, Patricia Gruner, Raquel E Gur, Ruben C Gur, Tiril P Gurholt, Lieuwe de Haan, Beathe Haatveit, Ben J Harrison, Catharina A Hartman, Sean N Hatton, Dirk J Heslenfeld, Odile A van den Heuvel, Ian B Hickie, Pieter J Hoekstra, Sarah Hohmann, Avram J Holmes, Martine Hoogman, Norbert Hosten, Fleur M Howells, Hilleke E Hulshoff Pol, Chaim Huyser, Neda Jahanshad, Anthony C James, Jiyang Jiang, Erik G Jönsson, John A Joska, Andrew J Kalnin, Karolinska Schizophrenia Project (KaSP) Consortium, Marieke Klein, Laura Koenders, Knut K Kolskår, Bernd Krämer, Jonna Kuntsi, Jim Lagopoulos, Luisa Lazaro, Irina S Lebedeva, Phil H Lee, Christine Lochner, Marise WJ Machielsen, Sophie Maingault, Nicholas G Martin, Ignacio Martínez-Zalacaín, David Mataix-Cols, Bernard Mazoyer, Brenna C McDonald, Colm McDonald, Andrew M McIntosh, Katie L McMahon, Genevieve McPhilemy, Dennis van der Meer, José M Menchón, Jilly Naaijen, Lars Nyberg, Jaap Oosterlaan, Yannis Paloyelis, Paul Pauli, Giulio Pergola, Edith Pomarol-Clotet, Maria J Portella, Joaquim Radua, Andreas Reif, Geneviève Richard, Joshua L Roffman, Pedro GP Rosa, Matthew D Sacchet, Perminder S Sachdev, Raymond Salvador, Salvador Sarró, Theodore D Satterthwaite, Andrew J Saykin, Mauricio H Serpa, Kang Sim, Andrew Simmons, Jordan W Smoller, Iris E Sommer, Carles Soriano-Mas, Dan J Stein, Lachlan T Strike, Philip R Szeszko, Henk S Temmingh, Sophia I Thomopoulos, Alexander S Tomyshev, Julian N Trollor, Anne Uhlmann, Ilya M Veer, Dick J Veltman, Aristotle Voineskos, Henry Völzke, Henrik Walter, Lei Wang, Yang Wang, Bernd Weber, Wei Wen, John D West, Lars T Westlye, Heather C Whalley, Steven CR Williams, Katharina Wittfeld, Daniel H Wolf, Margaret J Wright, Yuliya N Yoncheva, Marcus V Zanetti, Georg C Ziegler, Greig I de Zubicaray, Paul M Thompson, Eveline A Crone, Sophia Frangou, Christian K Tamnes
bioRxiv 2020.02.17.952010; doi: https://doi.org/10.1101/2020.02.17.952010
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Greater male than female variability in regional brain structure across the lifespan
Lara M Wierenga, Gaelle E Doucet, Danai Dima, Ingrid Agartz, Moji Aghajani, Theophilus N Akudjedu, Anton Albajes-Eizagirre, Dag Alnæs, Kathryn I Alpert, Ole A Andreassen, Alan Anticevic, Philip Asherson, Tobias Banaschewski, Nuria Bargallo, Sarah Baumeister, Ramona Baur-Streubel, Alessandro Bertolino, Aurora Bonvino, Dorret I Boomsma, Stefan Borgwardt, Josiane Bourque, Anouk den Braber, Daniel Brandeis, Alan Breier, Henry Brodaty, Rachel M Brouwer, Jan K Buitelaar, Geraldo F Busatto, Vince D Calhoun, Erick J Canales-Rodríguez, Dara M Cannon, Xavier Caseras, Francisco X Castellanos, Tiffany M Chaim-Avancini, Christopher RK Ching, Vincent P Clark, Patricia J Conrod, Annette Conzelmann, Fabrice Crivello, Christopher G Davey, Erin W Dickie, Stefan Ehrlich, Dennis van ’t Ent, Simon E Fisher, Jean-Paul Fouche, Barbara Franke, Paola Fuentes-Claramonte, Eco JC de Geus, Annabella Di Giorgio, David C Glahn, Ian H Gotlib, Hans J Grabe, Oliver Gruber, Patricia Gruner, Raquel E Gur, Ruben C Gur, Tiril P Gurholt, Lieuwe de Haan, Beathe Haatveit, Ben J Harrison, Catharina A Hartman, Sean N Hatton, Dirk J Heslenfeld, Odile A van den Heuvel, Ian B Hickie, Pieter J Hoekstra, Sarah Hohmann, Avram J Holmes, Martine Hoogman, Norbert Hosten, Fleur M Howells, Hilleke E Hulshoff Pol, Chaim Huyser, Neda Jahanshad, Anthony C James, Jiyang Jiang, Erik G Jönsson, John A Joska, Andrew J Kalnin, Karolinska Schizophrenia Project (KaSP) Consortium, Marieke Klein, Laura Koenders, Knut K Kolskår, Bernd Krämer, Jonna Kuntsi, Jim Lagopoulos, Luisa Lazaro, Irina S Lebedeva, Phil H Lee, Christine Lochner, Marise WJ Machielsen, Sophie Maingault, Nicholas G Martin, Ignacio Martínez-Zalacaín, David Mataix-Cols, Bernard Mazoyer, Brenna C McDonald, Colm McDonald, Andrew M McIntosh, Katie L McMahon, Genevieve McPhilemy, Dennis van der Meer, José M Menchón, Jilly Naaijen, Lars Nyberg, Jaap Oosterlaan, Yannis Paloyelis, Paul Pauli, Giulio Pergola, Edith Pomarol-Clotet, Maria J Portella, Joaquim Radua, Andreas Reif, Geneviève Richard, Joshua L Roffman, Pedro GP Rosa, Matthew D Sacchet, Perminder S Sachdev, Raymond Salvador, Salvador Sarró, Theodore D Satterthwaite, Andrew J Saykin, Mauricio H Serpa, Kang Sim, Andrew Simmons, Jordan W Smoller, Iris E Sommer, Carles Soriano-Mas, Dan J Stein, Lachlan T Strike, Philip R Szeszko, Henk S Temmingh, Sophia I Thomopoulos, Alexander S Tomyshev, Julian N Trollor, Anne Uhlmann, Ilya M Veer, Dick J Veltman, Aristotle Voineskos, Henry Völzke, Henrik Walter, Lei Wang, Yang Wang, Bernd Weber, Wei Wen, John D West, Lars T Westlye, Heather C Whalley, Steven CR Williams, Katharina Wittfeld, Daniel H Wolf, Margaret J Wright, Yuliya N Yoncheva, Marcus V Zanetti, Georg C Ziegler, Greig I de Zubicaray, Paul M Thompson, Eveline A Crone, Sophia Frangou, Christian K Tamnes
bioRxiv 2020.02.17.952010; doi: https://doi.org/10.1101/2020.02.17.952010

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