Normative Modeling of Brain Morphometry Across the Lifespan Using CentileBrain: Algorithm Benchmarking and Model Optimization
bioRxiv (Cold Spring Harbor Laboratory)
Abstract
We present an empirically benchmarked framework for sex-specific normative modeling of brain morphometry that can inform about the biological and behavioral significance of deviations from typical age-related neuroanatomical changes and support future study designs. This framework was developed using regional morphometric data from 37,407 healthy individuals (53% female; aged 3-90 years) following a comparative evaluation of eight algorithms and multiple covariate combinations pertaining to image acquisition and quality, parcellation software versions, global neuroimaging measures, and longitudinal stability. The Multivariate Factorial Polynomial Regression (MFPR) emerged as the preferred algorithm optimized using nonlinear polynomials for age and linear effects of global measures as covariates. The MFPR models showed excellent accuracy across the lifespan and within distinct age-bins, and longitudinal stability over a 2-year period. The performance of all MFPR models plateaued at sample sizes exceeding 3,000 study participants. The model and scripts described here are freely available through CentileBrain (https://centilebrain.org/).
Authors 98
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University of British Columbia · Djavad Mowafaghian Centre for Brain Health
Affiliation as printed
Djavad Mowafagian Centre for Brain Health, University of British Columbia, Vancouver, BC, Canada
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University of British Columbia · Djavad Mowafaghian Centre for Brain Health
Affiliation as printed
Djavad Mowafagian Centre for Brain Health, University of British Columbia, Vancouver, BC, Canada
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University of British Columbia · Djavad Mowafaghian Centre for Brain Health
Affiliation as printed
Djavad Mowafagian Centre for Brain Health, University of British Columbia, Vancouver, BC, Canada
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University of British Columbia · Djavad Mowafaghian Centre for Brain Health
Affiliation as printed
Djavad Mowafagian Centre for Brain Health, University of British Columbia, Vancouver, BC, Canada
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University of British Columbia · Djavad Mowafaghian Centre for Brain Health
Affiliation as printed
Djavad Mowafagian Centre for Brain Health, University of British Columbia, Vancouver, BC, Canada
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University of British Columbia · Djavad Mowafaghian Centre for Brain Health
Affiliation as printed
Djavad Mowafagian Centre for Brain Health, University of British Columbia, Vancouver, BC, Canada
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Icahn School of Medicine at Mount Sinai
Affiliation as printed
Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA
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Icahn School of Medicine at Mount Sinai
Affiliation as printed
Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA
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Icahn School of Medicine at Mount Sinai
Affiliation as printed
Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA
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University of Oslo · Region Stockholm · Karolinska Institutet · Diakonhjemmet Hospital · Stockholm Health Care Services
Affiliation as printed
Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet & Stockholm Health Care Services, Region Stockholm, Stockholm, Sweden
Department of Psychiatric Research, Diakonhjemmet Hospital, Oslo, Norway
Norwegian Centre for Mental Disorders Research (NORMENT), Institute of Clinical Medicine, University of Oslo, Oslo, Norway
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Affiliation as printed
Institute of Psychiatry, Psychology and Neuroscience, Social, Genetic and Developmental Psychiatry Center, King's College London, London, UK
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Marqués de Valdecilla University Hospital · Instituto de Investigación Marqués de Valdecilla
Affiliation as printed
Department of Psychiatry, Marqués de Valdecilla University Hospital, Valdecilla Biomedical Research Institute (IDIVAL), Santander, Spain
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Affiliation as printed
Laboratory of Neuropsychiatry, IRCCS Santa Lucia Foundation, Rome, Italy
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Central Institute of Mental Health
Affiliation as printed
Department of Child and Adolescent Psychiatry and Psychotherapy, Central Institute of Mental Health, Mannheim, Germany
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Central Institute of Mental Health
Affiliation as printed
Department of Child and Adolescent Psychiatry and Psychotherapy, Central Institute of Mental Health, Mannheim, Germany
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Affiliation as printed
Department of Basic Medical Science, Neuroscience and Sense Organs, University of Bari Aldo Moro, Bari, Italy
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Affiliation as printed
Department of Biological Psychology, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands
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Affiliation as printed
Translational Psychiatry Unit, Department of Psychiatry and Psychotherapy, University of Lübeck, Lübeck, Germany
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Affiliation as printed
Department of Psychiatry, University of Pennsylvania, Philadelphia, Pennsylvania, USA
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University of Zurich · Central Institute of Mental Health
Affiliation as printed
Department of Child and Adolescent Psychiatry and Psychotherapy, Central Institute of Mental Health, Mannheim, Germany
Department of Child and Adolescent Psychiatry, University of Zürich, Zurich, Switzerland
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Indiana University School of Medicine
Affiliation as printed
Department of Psychiatry, Indiana University School of Medicine, Indianapolis, Indiana, USA
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UNSW Sydney · Centre for Healthy Brain Ageing
Affiliation as printed
Centre for Healthy Brain Ageing (CHeBA), School of Psychiatry, University of New South Wales, Sydney, Australia
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Utrecht University · University Medical Center Utrecht · Vrije Universiteit Amsterdam
Affiliation as printed
Complex Trait Genetics, Center for Neurogenomics and Cognitive Research, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands
Department of Psychiatry, UMC Brain Center, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands
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Harvard University · Massachusetts General Hospital
Affiliation as printed
Department of Psychiatry, Massachusetts General Hospital, Boston, Massachusetts, USA
Department of Psychology, Center for Brain Science, Harvard University, Cambridge, Massachusetts, USA
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Radboud University Medical Center · Donders Institute for Brain, Cognition and Behaviour
Affiliation as printed
Department of Cognitive Neuroscience, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, The Netherlands
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Ollscoil na Gaillimhe – University of Galway
Affiliation as printed
Clinical Neuroimaging Laboratory, National University of Ireland Galway, Galway, Ireland
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Affiliation as printed
MRC Centre for Neuropsychiatric Genetics and Genomics, Division of Psychological Medicine and Clinical Neurosciences, Cardiff University, Cardiff, UK
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Uppsala University · Region Stockholm · Karolinska Institutet · Stockholm Health Care Services
Affiliation as printed
Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet & Stockholm Health Care Services, Region Stockholm, Stockholm, Sweden
Department of Medical Sciences, Psychiatry, Uppsala University, Uppsala, Sweden
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Centre Hospitalier Universitaire Sainte-Justine · Université de Montréal
Affiliation as printed
Department of Psychiatry and Addiction, Université de Montréal, CHU Ste Justine, Montréal, Canada
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Centro de Investigación Biomédica en Red de Salud Mental · Instituto de Biomedicina de Sevilla · Hospital Universitario Virgen del Rocío · Universidad de Sevilla
Affiliation as printed
Mental Health Research Networking Center (CIBERSAM), Madrid, Spain
University Hospital Virgen del Rocio, Seville, Spain; Department of Psychiatry, University of Seville, Institute of Biomedicine of Seville (IBIS), Seville, Spain
Department of Psychiatry, University of Seville, Institute of Biomedicine of Seville (IBIS), Seville, Spain
University Hospital Virgen del Rocio, Seville, Spain
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Université de Bordeaux · Institut des Maladies Neurodégénératives
Affiliation as printed
Institut des Maladies Neurodégénératives, Université de Bordeaux, Bordeaux, France
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Eveline A. Crone Aachen Institute of Psychology, Leiden University Leiden Institute for Brain and Cognition
Leiden University · Erasmus University Rotterdam
Affiliation as printed
Department of Psychology, Education and Child Studies, Erasmus University Rotterdam, Rotterdam, The Netherlands
Institute of Psychology, Leiden University, Leiden, The Netherlands; Leiden Institute for Brain and Cognition, Leiden University, Leiden, The Netherlands
Institute of Psychology, Leiden University, Leiden, The Netherlands
Leiden Institute for Brain and Cognition, Leiden University, Leiden, The Netherlands
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Queensland University of Technology
Affiliation as printed
School of Psychology & Counselling, Faculty of Health, Queensland University of Technology, Brisbane, Australia
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Casa Sollievo della Sofferenza
Affiliation as printed
Laboratory of Biological Psychiatry, Fondazione IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy
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Charité - Universitätsmedizin Berlin
Affiliation as printed
Division of Mind and Brain Research, Department of Psychiatry and Psychotherapy, Charité-Universitätsmedizin Berlin, Berlin, Germany
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Radboud University Nijmegen · Radboud University Medical Center · Max Planck Institute for Psycholinguistics · Donders Institute for Brain, Cognition and Behaviour
Affiliation as printed
Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, The Netherlands
Language and Genetics Department, Max Planck Institute for Psycholinguistics, Nijmegen, The Netherlands
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Radboud University Medical Center · Donders Institute for Brain, Cognition and Behaviour
Affiliation as printed
Department of Human Genetics, Radboud University Medical Center, Nijmegen, The Netherlands
Department of Psychiatry, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, The Netherlands
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Thomas Frodl Aachen
Affiliation as printed
University Clinics and Clinics for Psychiatry, Psychotherapy and Psychosomatic Medicine, RWTH Aachen University, Aachen, Germany
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Boston Children's Hospital · Harvard University
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Department of Psychiatry, Tommy Fuss Center for Neuropsychiatric Disease Research Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts, USA
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Affiliation as printed
Department of Psychiatry and Psychotherapy, University of Muenster, Muenster, Germany
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Affiliation as printed
Section for Experimental Psychopathology and Neuroimaging, Department of General Psychiatry, Heidelberg University, Heidelberg, Germany
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Affiliation as printed
Department of Psychiatry, Yale University, New Haven, Connecticut, USA
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Affiliation as printed
Department of Psychiatry, University of Pennsylvania, Philadelphia, Pennsylvania, USA
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Affiliation as printed
Department of Psychiatry, University of Pennsylvania, Philadelphia, Pennsylvania, USA
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The University of Melbourne · Melbourne Health
Affiliation as printed
Melbourne Neuropsychiatry Centre, Department of Psychiatry, The University of Melbourne & Melbourne Health, Melbourne, Australia
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University of California San Diego
Affiliation as printed
Center for Multimodal Imaging and Genetics, University of California San Diego, La jolla, California, USA
Center for Multimodal Imaging and Genetics, University of California San Diego, La Jolla, California, USA
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Affiliation as printed
Brain and Mind Centre, University of Sydney, Sydney, Australia
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Affiliation as printed
Neuroscience Institute, University of Cape Town, Cape Town, South Africa
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Utrecht University · University Medical Center Utrecht
Affiliation as printed
Department of Psychiatry, UMC Brain Center, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands
Department of Psychology, Utrecht University, Utrecht, The Netherlands
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Amsterdam UMC Location University of Amsterdam · De Bascule
Affiliation as printed
Department of Child and Adolescent Psychiatry, Academic Medical Centre/De Bascule, Amsterdam, The Netherlands
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University of California San Diego
Affiliation as printed
Center for Human Development, Departments of Cognitive Science, Psychiatry, and Radiology, University of California, San Diego, USA
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UNSW Sydney · Centre for Healthy Brain Ageing
Affiliation as printed
Centre for Healthy Brain Ageing (CHeBA), School of Psychiatry, University of New South Wales, Sydney, Australia
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Affiliation as printed
Department of Neuropsychiatry, University of Cape Town, Cape Town, South Africa
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Icahn School of Medicine at Mount Sinai
Affiliation as printed
Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA
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UNSW Sydney · Centre for Healthy Brain Ageing
Affiliation as printed
Centre for Healthy Brain Ageing (CHeBA), School of Psychiatry, University of New South Wales, Sydney, Australia
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University Medical Center Utrecht
Affiliation as printed
Department of Psychiatry and Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, The Netherlands
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Affiliation as printed
Institute of Psychiatry, Psychology and Neuroscience, Social, Genetic and Developmental Psychiatry Center, King's College London, London, UK
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University of the Sunshine Coast
Affiliation as printed
Sunshine Coast Mind and Neuroscience - Thompson Institute, University of the Sunshine Coast, Queensland, Australia
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Affiliation as printed
Department of Child and Adolescent Psychiatry and Psychology, Hospital Clínic Barcelona, Barcelona, Spain
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Mental Health Research Center of Russian Academy of Medical Sciences
Affiliation as printed
Mental Health Research Center, Moscow, Russia
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Affiliation as printed
SA MRC Unit on Risk and Resilience in Mental Disorders, Department of Psychiatry, Stellenbosch University, Stellenbosch, South Africa
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QIMR Berghofer Medical Research Institute
Affiliation as printed
Queensland Institute of Medical Research, Berghofer Medical Research Institute, Brisbane, Australia
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Université de Bordeaux · Institut des Maladies Neurodégénératives
Affiliation as printed
Institut des Maladies Neurodégénératives, Université de Bordeaux, Bordeaux, France
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Indiana University School of Medicine
Affiliation as printed
Department of Radiology and Imaging Sciences, Indiana University School of Medicine, Indianapolis, Indiana, USA
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Ollscoil na Gaillimhe – University of Galway
Affiliation as printed
Centre for Neuroimaging & Cognitive Genomics (NICOG), NCBES Galway Neuroscience Centre, National University of Ireland Galway, Galway, Ireland
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Queensland University of Technology
Affiliation as printed
School of Clinical Sciences, Centre for Biomedical Technologies, Queensland University of Technology, Brisbane, Australia
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Affiliation as printed
Department of Neuropsychiatry, Kyushu University, Fukuoka, Japan
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Affiliation as printed
Department of Radiation Sciences, Umeå Center for Functional Brain Imaging, Umeå University, Umeå, Sweden; Department of Integrative Medical Biology, Umeå University, Umeå, Sweden
Department of Integrative Medical Biology, Umeå University, Umeå, Sweden
Department of Radiation Sciences, Umeå Center for Functional Brain Imaging, Umeå University, Umeå, Sweden
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Affiliation as printed
Laboratory of Neuropsychiatry, IRCCS Santa Lucia Foundation, Rome, Italy
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Universitat Autònoma de Barcelona · Hospital de Sant Pau · Centro de Investigación Biomédica en Red de Salud Mental
Affiliation as printed
Department of Psychiatry, Hospital de la Santa Creu iSant Pau, Institutd' Investigació Biomèdica SantPau, Universitat Autònomade Barcelona (UAB), Barcelona, Spain
Mental Health Research Networking Center (CIBERSAM), Madrid, Spain
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Southwest University · Beijing Normal University
Affiliation as printed
Faculty of Psychology, Southwest University, Chongqing, PR China
Key Laboratory of Cognition and Personality, Southwest University, Ministry of Education, Chongqing, PR China
Southwest University Branch, Collaborative Innovation Center of Assessment Toward Basic Education Quality, Beijing Normal University, Beijing, PR China
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Harvard University · Massachusetts General Hospital
Affiliation as printed
Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA
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UNSW Sydney · Centre for Healthy Brain Ageing
Affiliation as printed
Centre for Healthy Brain Ageing (CHeBA), School of Psychiatry, University of New South Wales, Sydney, Australia
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University of British Columbia · Djavad Mowafaghian Centre for Brain Health
Affiliation as printed
Djavad Mowafagian Centre for Brain Health, University of British Columbia, Vancouver, BC, Canada
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Affiliation as printed
Department of Psychiatry, University of Pennsylvania, Philadelphia, Pennsylvania, USA
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Indiana University School of Medicine
Affiliation as printed
Department of Radiology and Imaging Sciences, Indiana University School of Medicine, Indianapolis, Indiana, USA
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King's College London · Fudan University · Charité - Universitätsmedizin Berlin
Affiliation as printed
Centre for Population Neuroscience and Precision Medicine (PONS), Institute of Psychiatry, Psychology, and Neuroscience, Social, Genetic & Developmental Psychiatry Centre, King's College London, London, UK; Institute for Science and Technology of Brain-inspired Intelligence, Fudan University, Shanghai, PR China; Centre for Population Neuroscience and Stratified Medicine (PONS), Charite Mental Health, Department of Psychiatry and Psychotherapy, CCM, Charite Universitätsmedizin Berlin, Berlin, Germany
Centre for Population Neuroscience and Precision Medicine (PONS), Institute of Psychiatry, Psychology, and Neuroscience, Social, Genetic & Developmental Psychiatry Centre, King's College London, London, UK
Institute for Science and Technology of Brain-inspired Intelligence, Fudan University, Shanghai, PR China
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Region Stockholm · Karolinska Institutet · Stockholm Health Care Services
Affiliation as printed
Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet & Stockholm Health Care Services, Region Stockholm, Stockholm, Sweden
Department of Physiology and Pharmacology, Karolinska Institute, Stockholm, Sweden
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Affiliation as printed
Institute of Mental Health, Singapore
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Massachusetts General Hospital
Affiliation as printed
Center for Genomic Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA
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Affiliation as printed
University of Texas Health Harris County Psychiatric Center, Houston, Texas, USA
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University Medical Center Groningen · University of Groningen
Affiliation as printed
Department of Biomedical Sciences of Cells and Systems, Rijksuniversiteit Groningen, University Medical Center Groningen, Groningen, The Netherlands
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Affiliation as printed
Laboratory of Neuropsychiatry, IRCCS Santa Lucia Foundation, Rome, Italy
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Affiliation as printed
SA MRC Unit on Risk and Resilience in Mental Disorders, Department of Psychiatry and Neuroscience Institute, University of Cape Town, Cape Town, South Africa
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University of Oslo · Diakonhjemmet Hospital
Affiliation as printed
Department of Psychiatric Research, Diakonhjemmet Hospital, Oslo, Norway
Norwegian Centre for Mental Disorders Research (NORMENT), Institute of Clinical Medicine, University of Oslo, Oslo, Norway
PROMENTA Research Center, Department of Psychology, University of Oslo, Oslo, Norway
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University of Southern California
Affiliation as printed
Genetics Center, Stevens Institute for Neuroimaging and Informatics, Keck USC School of Medicine, Marina del Rey, California, USA
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Mental Health Research Center of Russian Academy of Medical Sciences
Affiliation as printed
Mental Health Research Center, Moscow, Russia
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Consejo Superior de Investigaciones Científicas · Marqués de Valdecilla University Hospital · Instituto de Investigación Marqués de Valdecilla · Instituto de Física de Cantabria
Affiliation as printed
Department of Radiology, Marqués de Valdecilla University Hospital, Valdecilla Biomedical Research Institute (IDIVAL), Santander, Spain; Advanced Computing and e-Science, Instituto de Física de Cantabria (UC-CSIC), Santander, Spain
Advanced Computing and e-Science, Instituto de Física de Cantabria (UC-CSIC), Santander, Spain
Department of Radiology, Marqués de Valdecilla University Hospital, Valdecilla Biomedical Research Institute (IDIVAL), Santander, Spain
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UNSW Sydney · Centre for Healthy Brain Ageing
Affiliation as printed
Centre for Healthy Brain Ageing (CHeBA), School of Psychiatry, University of New South Wales, Sydney, Australia
Department of Developmental Disability Neuropsychiatry, School of Psychiatry, University of New South Wales, Sydney, Australia
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Affiliation as printed
Department of Biological Psychology, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands
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Amsterdam Neuroscience · Amsterdam University Medical Centers · Vrije Universiteit Amsterdam
Affiliation as printed
Department of Anatomy & Neurosciences, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam Neuroscience, Amsterdam, The Netherlands
Department of Psychiatry, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam Neuroscience, Amsterdam, The Netherlands
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University of California, Irvine
Affiliation as printed
Department of Psychiatry and Human Behavior, University of California, Irvine, California, USA
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Erasmus MC · Erasmus University Rotterdam
Affiliation as printed
Department of Child and Adolescent Psychiatry/Psychology, Erasmus University Medical Centre, Rotterdam, The Netherlands
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Affiliation as printed
Laboratory of Neuropsychiatry, IRCCS Santa Lucia Foundation, Rome, Italy
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Amsterdam Neuroscience · Amsterdam University Medical Centers · Vrije Universiteit Amsterdam
Affiliation as printed
Department of Psychiatry, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam Neuroscience, Amsterdam, The Netherlands
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Charité - Universitätsmedizin Berlin
Affiliation as printed
Division of Mind and Brain Research, Department of Psychiatry and Psychotherapy, Charité-Universitätsmedizin Berlin, Berlin, Germany
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Affiliation as printed
Department of Radiology, Medical College of Wisconsin, Milwaukee, Wisconsin, USA
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University of Bonn · University Hospital Bonn
Affiliation as printed
Institute for Experimental Epileptology and Cognition Research, University of Bonn Germany, Bonn, Germany; University Hospital Bonn, Bonn, Germany
Institute for Experimental Epileptology and Cognition Research, University of Bonn Germany, Bonn, Germany
University Hospital Bonn, Bonn, Germany
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