The bidirectional effects between cognitive ability and brain morphology: A life course Mendelian randomization analysis
Abstract
Introduction: Little is understood about the dynamic interplay between brain morphology and cognitive ability across the life course. Additionally, most existing research has focused on global morphology measures such as estimated total intracranial volume, mean thickness, and total surface area. Methods: Mendelian randomization was used to estimate the bidirectional effects between cognitive ability, global and regional measures of cortical thickness and surface area, estimated total intracranial volume, total white matter, and the volume of subcortical structures (N=37,864). Analyses were stratified for developmental periods (childhood, early adulthood, mid-to-late adulthood; age range: 8-81 years). Results: The earliest effects were observed in childhood and early adulthood in the frontoparietal lobes. A bidirectional relationship was identified between higher cognitive ability, larger estimated total intracranial volume (childhood, mid-to-late adulthood) and total surface area (all life stages). A thicker posterior cingulate cortex and a larger surface area in the caudal middle frontal cortex and temporal pole were associated with greater cognitive ability. Contrary, a thicker temporal pole was associated with lower cognitive ability. Discussion: Stable effects of cognitive ability on brain morphology across the life course suggests that childhood is potentially an important window for intervention.
Authors 29
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Roxanna Korologou‐Linden corresponding
University of Bristol · MRC Integrative Epidemiology Unit
Affiliation as printed
Medical Research Council Integrative Epidemiology Unit, University of Bristol, BS8 2BN, United Kingdom
Population Health Sciences, Bristol Medical School, University of Bristol, Barley House, Oakfield Grove, Bristol, BS8 2BN, United Kingdom
Population Health Sciences, Bristol Medical School, University of Bristol, Barley House, Oakfield Grove, Bristol, BS8 BN, United Kingdom
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Affiliation as printed
Department of Epidemiology, Erasmus MC University Medical Center Rotterdam, Rotterdam, the Netherlands
The Generation R Study Group, Erasmus MC University Medical Center Rotterdam, Rotterdam, the Netherlands
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Leiden University Medical Center · Erasmus MC
Affiliation as printed
Department of Child and Adolescent Psychiatry and Psychology, Erasmus MC University Medical Center Rotterdam, Rotterdam, the Netherlands
Department of Epidemiology, Erasmus MC University Medical Center Rotterdam, Rotterdam, the Netherlands
Molecular Epidemiology, Department of Biomedical Data Sciences, Leiden University Medical Center, Leiden, the Netherlands
The Generation R Study Group, Erasmus MC University Medical Center Rotterdam, Rotterdam, the Netherlands
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Leiden University Medical Center · Erasmus MC · National Institute of Mental Health
Affiliation as printed
Department of Child and Adolescent Psychiatry and Psychology, Erasmus MC University Medical Center Rotterdam, Rotterdam, the Netherlands
Department of Radiology and Nuclear Medicine, Erasmus University School of Medicine
Molecular Epidemiology, Department of Biomedical Data Sciences, Leiden University Medical Center, Leiden, the Netherlands
Section on Social and Cognitive Developmental Neuroscience, National Institute of Mental Health, Bethesda, Maryland, USA
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Heidelberg University · Central Institute of Mental Health · Medizinische Fakultät Mannheim
Affiliation as printed
Department of Child and Adolescent Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Square J5, 68159 Mannheim, Germany
Department of Child and Adolescent Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Square J5, 6815 Mannheim, Germany
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Affiliation as printed
Discipline of Psychiatry, School of Medicine and Trinity College Institute of Neuroscience, Trinity College Dublin, Dublin, Ireland
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Affiliation as printed
Centre for Population Neuroscience and Precision Medicine (PONS), Institute of Psychiatry, Psychology & Neuroscience, SGDP Centre, King's College London, United Kingdom
Centre for Population Neuroscience and Precision Medicine (PONS), Institute of Psychiatry, Psychology & Neuroscience, SGDP Centre, King’s College London, United Kingdom
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Affiliation as printed
Department of Psychology, School of Social Sciences, University of Mannheim, 68131 Mannheim, Germany
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Affiliation as printed
Departments of Psychiatry and Psychology, University of Vermont, 05405 Burlington, Vermont, USA
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Affiliation as printed
Sir Peter Mansfield Imaging Centre School of Physics and Astronomy, University of Nottingham, University Park, Nottingham, United Kingdom
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Humboldt-Universität zu Berlin · Charité - Universitätsmedizin Berlin
Affiliation as printed
Department 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
Department 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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Physikalisch-Technische Bundesanstalt
Affiliation as printed
Physikalisch-Technische Bundesanstalt (PTB), Braunschweig and Berlin, Germany
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École Normale Supérieure Paris-Saclay · Centre National de la Recherche Scientifique · Inserm · Université Paris-Saclay · Trajectoires développementales & psychiatrie · Centre Borelli
Affiliation as printed
Institut National de la Santé et de la Recherche Médicale, INSERM U1299 "Developmental trajectories & psychiatry"; Ecole Normale supérieure Paris-Saclay, Université Paris-Saclay, CNRS, Centre Borelli; Gif-sur-Yvette, France
Ecole Normale supérieure Paris-Saclay, Université Paris-Saclay, CNRS, Centre Borelli
Gif-sur-Yvette, France
Institut National de la Santé et de la Recherche Médicale, INSERM U1299 “Developmental trajectories & psychiatry”
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École Normale Supérieure Paris-Saclay · Centre National de la Recherche Scientifique · Inserm · Université Paris-Saclay · Trajectoires développementales & psychiatrie · Centre Borelli
Affiliation as printed
Etablissement Public de Santé (EPS) Barthélemy Durand, Etampes, France
Institut National de la Santé et de la Recherche Médicale, INSERM U1299 "Developmental trajectories & psychiatry"; Ecole Normale supérieure Paris-Saclay, Université Paris-Saclay, CNRS, Centre Borelli; Gif-sur-Yvette, France
Ecole Normale supérieure Paris-Saclay, Université Paris-Saclay, CNRS, Centre Borelli
Gif-sur-Yvette, France
Institut National de la Santé et de la Recherche Médicale, INSERM U1299 “Developmental trajectories & psychiatry”
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Heidelberg University · Commissariat à l'Énergie Atomique et aux Énergies Alternatives · Université Paris-Saclay · CEA Paris-Saclay - Etablissement de Saclay · Central Institute of Mental Health · CEA Paris-Saclay · Medizinische Fakultät Mannheim
Affiliation as printed
Department of Child and Adolescent Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Square J5, 68159 Mannheim, Germany
Institute of Cognitive and Clinical Neuroscience, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Square J5, Mannheim, Germany
NeuroSpin, CEA, Université Paris-Saclay, F-91191 Gif-sur-Yvette, France
Department of Child and Adolescent Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Square J5, 6815 Mannheim, Germany
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Christian-Albrechts-Universität zu Kiel · University Hospital Schleswig-Holstein
Affiliation as printed
Institute of Medical Psychology and Medical Sociology, University Medical Center Schleswig Holstein, Kiel University, Kiel, Germany
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University of Toronto · Centre Hospitalier Universitaire Sainte-Justine · Université de Montréal
Affiliation as printed
Department of Psychiatry, Faculty of Medicine, University of Montreal, Montreal, Quebec, Canada and Centre hospitalier universitaire Sainte-Justine, University of Montreal, Montreal, Quebec, Canada
Departments of Psychology and Psychiatry, University of Toronto, Toronto, Ontario, M6A 2E1, Canada
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Affiliation as printed
Department of Child and Adolescent Psychiatry and Psychotherapy, University Medical Centre Göttingen, von-Siebold-Str. 5, 37075, Göttingen, Germany
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Heidelberg University · Central Institute of Mental Health · Medizinische Fakultät Mannheim
Affiliation as printed
Department of Child and Adolescent Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Square J5, 68159 Mannheim, Germany
Department of Child and Adolescent Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Square J5, 6815 Mannheim, Germany
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Neuroimaging Center · Technische Universität Dresden
Affiliation as printed
Department of Psychiatry and Neuroimaging Center, Technische Universität Dresden, Dresden, Germany
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Affiliation as printed
Department of Education and Psychology, Freie Universität Berlin, Berlin, Germany
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Humboldt-Universität zu Berlin · Charité - Universitätsmedizin Berlin
Affiliation as printed
Department 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
Department 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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Humboldt-Universität zu Berlin · Freie Universität Berlin · Charité - Universitätsmedizin Berlin
Affiliation as printed
Department of Education and Psychology, Freie Universität Berlin, Berlin, Germany
Department 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
Department 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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Affiliation as printed
School of Psychology and Global Brain Health Institute, Trinity College Dublin, Ireland
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King's College London · Fudan University · Humboldt-Universität zu Berlin · Charité - Universitätsmedizin Berlin · Leibniz Institute for Neurobiology
Affiliation as printed
Centre for Population Neuroscience and Precision Medicine (PONS), Institute of Psychiatry, Psychology & Neuroscience, SGDP Centre, King's College London, United Kingdom
PONS Research Group, Dept of Psychiatry and Psychotherapy, Campus Charite Mitte, Humboldt University, Berlin and Leibniz Institute for Neurobiology, Magdeburg, Germany, and Institute for Science and Technology of Brain-inspired Intelligence (ISTBI), Fudan University, Shanghai, P.R. China
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University of Bristol · MRC Integrative Epidemiology Unit
Affiliation as printed
Medical Research Council Integrative Epidemiology Unit, University of Bristol, BS8 2BN, United Kingdom
Population Health Sciences, Bristol Medical School, University of Bristol, Barley House, Oakfield Grove, Bristol, BS8 2BN, United Kingdom
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Affiliation as printed
Population Health Sciences, Bristol Medical School, University of Bristol, Barley House, Oakfield Grove, Bristol, BS8 2BN, United Kingdom
Population Health Sciences, Bristol Medical School, University of Bristol, Barley House, Oakfield Grove, Bristol, BS8 BN, United Kingdom
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Norwegian University of Science and Technology · University of Bristol · MRC Integrative Epidemiology Unit · University College London
Affiliation as printed
Department of Statistical Sciences, University College London, London WC1E 6BT, UK
Division of Psychiatry, University College London, Maple House, 149 Tottenham Court Rd, London W1T 7NF
K.G. Jebsen Center for Genetic Epidemiology, Department of Public Health and Nursing, NTNU, Norwegian University of Science and Technology, Norway
Medical Research Council Integrative Epidemiology Unit, University of Bristol, BS8 2BN, United Kingdom
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University of Bristol · MRC Integrative Epidemiology Unit
Affiliation as printed
Medical Research Council Integrative Epidemiology Unit, University of Bristol, BS8 2BN, United Kingdom
Population Health Sciences, Bristol Medical School, University of Bristol, Barley House, Oakfield Grove, Bristol, BS8 2BN, United Kingdom
Population Health Sciences, Bristol Medical School, University of Bristol, Barley House, Oakfield Grove, Bristol, BS8 BN, United Kingdom
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