Brain age prediction in generalized anxiety disorder using a convolutional neural network
Translational Psychiatry, vol. 16
Abstract
Higher predicted brain age difference has been associated with several psychiatric disorders. Generalized anxiety disorder (GAD) is associated with markers of accelerated aging. In this study, we determined brain predicted age difference (PAD) in individuals with GAD and healthy controls (HC) as well as group differences in PAD variability using voxel-wise structural MRI. The training dataset included 3511 controls, and the testing dataset included 1595 individuals with GAD and 4552 HC from the ENIGMA-Anxiety GAD Working Group. A convolutional neural network model using four input modalities per subject and a model ensemble approach was used to predict brain age. The PAD was then calculated by subtracting chronological age from the predicted age. Model performance was consistent with other image-based brain age prediction models with similar accuracy across the training set (mean absolute error (MAE) = 2.95 years) and HC in the testing set (MAE = 2.94). We found no evidence of accelerated brain aging in individuals with GAD compared to individuals without GAD, though we did find evidence for greater variation in PAD for individuals with GAD (Levene's test: W = 442.98, p < 0.001) and evidence for greater variability in PAD of those with GAD over 25 years of age. In several exploratory analyses, we found that symptom severity related significantly to PAD, even after controlling for medication and comorbid diagnoses, echoing previous brain age research. These findings underscore the need for consideration of heterogeneity and dimensionality of psychopathology when examining brain age predicted differences.
Authors 90
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Corey Richier corresponding
University of Illinois Urbana-Champaign · National Institute of Mental Health
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Department of Psychology, University of Illinois at Urbana-Champaign, Urbana, IL, USA. coreyjr2@illinois.edu
Emotion and Development Branch, National Institute of Mental Health, Bethesda, MD, USA. coreyjr2@illinois.edu
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National Institute of Mental Health
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Emotion and Development Branch, National Institute of Mental Health, Bethesda, MD, USA
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National Institute of Mental Health · Erasmus University Rotterdam
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Department of Psychology, Education and Child Studies, Erasmus University Rotterdam, Rotterdam, The Netherlands
Emotion and Development Branch, National Institute of Mental Health, Bethesda, MD, USA
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National Institute of Mental Health · Catholic University of America
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Department of Psychology, The Catholic University of America, Washington, DC, USA
Emotion and Development Branch, National Institute of Mental Health, Bethesda, MD, USA
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National Institute of Mental Health
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Emotion and Development Branch, National Institute of Mental Health, Bethesda, MD, USA
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Leiden University, Institute of Education & Child Studies, Section Forensic Family & Youth Care, Leiden, The Netherlands
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Willem B. Bruin Aachen Institute of Education and Child Studies Section Forensic Family & Youth Care
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Leiden University, Institute of Education & Child Studies, Section Forensic Family & Youth Care, Leiden, The Netherlands
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HMU Health and Medical University Erfurt
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Department of Psychology, HMU Health and Medical University Erfurt, Erfurt, Germany
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Universitat Autònoma de Barcelona · Instituto de Salud Carlos III · Hospital de Sant Pau · Centro de Investigación Biomédica en Red de Salud Mental · Institut de Recerca Sant Pau
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Centro de Investigación Biomédica En Red en Salud Mental (CIBERSAM), Instituto de Salud Carlos III, Madrid, Spain
Department of Psychiatry and Forensic Medicine, Universitat Autònoma de Barcelona (UAB), Bellaterra, Spain
Sant Pau Mental Health Research Group, Institut de Recerca Sant Pau (IR SANT PAU), Barcelona, Spain
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. Sant Pau Mental Health Research Group , Institut de Recerca Sant Pau (IR SANT PAU) , Barcelona , Spain
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Instituto de Salud Carlos III · Hospital de Sant Pau · Centro de Investigación Biomédica en Red de Salud Mental · Institut de Recerca Sant Pau
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Centro de Investigación Biomédica En Red en Salud Mental (CIBERSAM), Instituto de Salud Carlos III, Madrid, Spain
Sant Pau Mental Health Research Group, Institut de Recerca Sant Pau (IR SANT PAU), Barcelona, Spain
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Menninger Department of Psychiatry and Behavioral Sciences, Baylor College of Medicine, Houston, TX, USA
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Menninger Department of Psychiatry and Behavioral Sciences, Baylor College of Medicine, Houston, TX, USA
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Universidade Federal de São Paulo
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LiNC, Department of Psychiatry, Federal University of São Paulo, São Paulo, Brazil
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Universidade Federal de São Paulo
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LiNC, Department of Psychiatry, Federal University of São Paulo, São Paulo, Brazil
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Universidade Federal do Rio Grande do Sul · Hospital de Clínicas de Porto Alegre
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Section on Negative Affect and Social Processes, Hospital de Clínicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil
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Boys Town National Research Hospital
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Center for Neurobehavioral Research, Boys Town National Research Hospital, Boys Town, NE, USA
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Department of Psychiatry, NYU School of Medicine, New York University, New York, NY, USA
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Department of Psychology, Penn State University, University Park, PA, USA
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Department of Psychiatry and Behavioral Health, The Ohio State University, Columbus, OH, USA
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Department of Psychiatry & Behavioral Neuroscience, University of Cincinnati, Cincinnati, OH, USA
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Department of Psychiatry & Behavioral Neuroscience, University of Cincinnati, Cincinnati, OH, USA
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Technische Universität Dresden
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Behavioral Epidemiology, Institute of Clinical Psychology and Psychotherapy, TUD Dresden University of Technology, Dresden, Germany
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University of Southern California
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Imaging Genetics Center, Mark and Mary Stevens Neuroimaging and Informatics Institute, Keck School of Medicine, University of Southern California, Marina del Rey, CA, USA
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University of Southern California
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Imaging Genetics Center, Mark and Mary Stevens Neuroimaging and Informatics Institute, Keck School of Medicine, University of Southern California, Marina del Rey, CA, USA
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Brigham Young University · Harvard University · Massachusetts General Hospital
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Center for Brain Science & Department of Psychology, Harvard University, Cambridge, MA, USA
Department of Psychiatry, Massachusetts General Hospital, Boston, MA, USA
Psychology Department & Neuroscience Center, Brigham Young University, Provo, UT, USA
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Massachusetts General Hospital
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Department of Psychiatry, Massachusetts General Hospital, Boston, MA, USA
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The University of Texas Health Science Center at Houston
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Center Of Excellence On Mood Disorders, Louis A. Faillace, MD, Department of Psychiatry and Behavioral Sciences, The University of Texas Health Science Center at Houston, Houston, TX, USA
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The University of Texas Health Science Center at Houston
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Center Of Excellence On Mood Disorders, Louis A. Faillace, MD, Department of Psychiatry and Behavioral Sciences, The University of Texas Health Science Center at Houston, Houston, TX, USA
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The University of Texas Health Science Center at Houston
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Center Of Excellence On Mood Disorders, Louis A. Faillace, MD, Department of Psychiatry and Behavioral Sciences, The University of Texas Health Science Center at Houston, Houston, TX, USA
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The University of Texas Health Science Center at Houston
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Center Of Excellence On Mood Disorders, Louis A. Faillace, MD, Department of Psychiatry and Behavioral Sciences, The University of Texas Health Science Center at Houston, Houston, TX, USA
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Hartford Hospital · Yale University
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Department of Psychiatry, Yale School of Medicine, New Haven, CT, USA
Olin Neuropsychiatry Research Center, Institute of Living, Hartford Hospital, Hartford, CT, USA
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Hartford Hospital · Yale University
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Anxiety Disorders Center, Institute of Living, Hartford Hospital, Hartford, CT, USA
Department of Psychiatry, Yale School of Medicine, New Haven, CT, USA
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University of Milan · Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico
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Department of Neurosciences and Mental Health, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy
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Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico
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Department of Neurosciences and Mental Health, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
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Institute of Medical Psychology and Systems Neuroscience, University of Muenster, Muenster, Germany
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Institute of Medical Psychology and Systems Neuroscience, University of Muenster, Muenster, Germany
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Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA, USA
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Department Psychology, University of Pittsburgh, Pittsburgh, PA, USA
Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA, USA
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Universidade Federal do Rio Grande do Sul · Hospital de Clínicas de Porto Alegre
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Anxiety Disorder Program, Hospital de Clínicas de Porto Alegre, Department of Psychiatry, Federal University of Rio Grande do Sul, Porto Alegre, Brazil
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Vita-Salute San Raffaele University · IRCCS Ospedale San Raffaele
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Neuroimaging Research Unit, Institute of Experimental Neurology, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milan, Italy
Vita-Salute San Raffaele University, Milan, Italy
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Neuroimaging Research Unit, Institute of Experimental Neurology, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milan, Italy
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Vita-Salute San Raffaele University · IRCCS Ospedale San Raffaele
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Neuroimaging Research Unit, Institute of Experimental Neurology, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milan, Italy
Vita-Salute San Raffaele University, Milan, Italy
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Vita-Salute San Raffaele University · IRCCS Ospedale San Raffaele · Istituto di Ricovero e Cura a Carattere Scientifico San Raffaele
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Neuroimaging Research Unit, Institute of Experimental Neurology, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milan, Italy
Neurology Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy
Neurophysiology Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy
Neurorehabilitation Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy
Vita-Salute San Raffaele University, Milan, Italy
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University of Belgrade · Institute of Mental Health
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Department of Psychiatry, School of Medicine, University of Belgrade, Belgrade, Serbia
Institute of Mental Health, University of Belgrade, Belgrade, Serbia
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University of Belgrade · Institute of Mental Health
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Institute of Mental Health, University of Belgrade, Belgrade, Serbia
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National Institute of Mental Health
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Emotion and Development Branch, National Institute of Mental Health, Bethesda, MD, USA
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National Institute of Mental Health
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Emotion and Development Branch, National Institute of Mental Health, Bethesda, MD, USA
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National Institute of Mental Health
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Emotion and Development Branch, National Institute of Mental Health, Bethesda, MD, USA
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Johns Hopkins University · National Institute of Mental Health
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Department of Biostatistics, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA
Emotion and Development Branch, National Institute of Mental Health, Bethesda, MD, USA
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Stanford Medicine · Stanford University
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Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA, USA
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National Institute of Mental Health
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Emotion and Development Branch, National Institute of Mental Health, Bethesda, MD, USA
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Universitätsmedizin Greifswald · German Center for Neurodegenerative Diseases · Universität Greifswald
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Department of Psychiatry and Psychotherapy, University Medicine Greifswald, Greifswald, Germany
German Center for Neurodegenerative Diseases (DZNE), Site Rostock/Greifswald, Greifswald, Germany
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Universitätsmedizin Greifswald · German Center for Neurodegenerative Diseases · Universität Greifswald
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Department of Psychiatry and Psychotherapy, University Medicine Greifswald, Greifswald, Germany
German Center for Neurodegenerative Diseases (DZNE), Site Rostock/Greifswald, Greifswald, Germany
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Universitätsmedizin Greifswald · Universität Greifswald
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Department of Psychiatry and Psychotherapy, University Medicine Greifswald, Greifswald, Germany
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Universitätsmedizin Greifswald · Universität Greifswald
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Institute for Community Medicine, University Medicine Greifswald, Greifswald, Germany
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Universitätsmedizin Greifswald · Universität Greifswald
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Institute for Diagnostic Radiology and Neuroradiology, University Medicine Greifswald, Greifswald, Germany
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Center for Neuromodulation in Depression and Stress, University of Pennsylvania, Philadelphia, PA, USA
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National Institutes of Health · National Institute of Mental Health
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Section on Neurobiology of Fear and Anxiety, National Institute of Mental Health, Bethesda, MD, USA
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Department of Biomedical Engineering, Stony Brook University, Stony Brook, NY, USA
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Department of Physics, Stony Brook University, Stony Brook, NY, USA
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Brighton and Sussex Medical School · University of Sussex
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Department of Neuroscience, Brighton and Sussex Medical School, University of Sussex, Brighton, UK
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Department of Psychology, Brunel University London, Uxbridge, UK
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"Enrico Fermi" Research Center, Rome, Italy
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Department of Psychology, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK
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Fondazione Santa Lucia · Sapienza University of Rome
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Department of Psychology, Sapienza University of Rome, Rome, Italy
IRCCS Santa Lucia Foundation, Rome, Italy
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The University of Texas at Austin
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Department of Psychiatry and Behavioral Sciences, The University of Texas at Austin Dell Medical School, Austin, TX, USA
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Laureate Institute for Brain Research
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Laureate Institute for Brain Research, Tulsa, OK, USA
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University of California San Diego
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Department of Psychiatry, School of Medicine and Herbert Wertheim School of Public Health, University of California, San Diego, La Jolla, CA, USA
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Department of Psychiatry, University of Pennsylvania, Philadelphia, PA, USA
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Department of Psychiatry, University of Pennsylvania, Philadelphia, PA, USA
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Department of Psychology, Vanderbilt University, Nashville, TN, USA
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University of Minnesota · University of Pennsylvania
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Department of Pediatrics, University of Minnesota, Minneapolis, MN, USA
Department of Psychiatry, University of Pennsylvania, Philadelphia, PA, USA
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Department of Psychiatry, University of Pennsylvania, Philadelphia, PA, USA
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Washington University in St. Louis
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Department of Psychiatry, Washington University, St. Louis, MO, USA
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Washington University in St. Louis
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Department of Psychiatry, Washington University, St. Louis, MO, USA
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Washington University in St. Louis
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Department of Psychiatry, Washington University, St. Louis, MO, USA
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Washington University in St. Louis
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Department of Psychiatry, Washington University, St. Louis, MO, USA
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National Institute of Mental Health
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Machine Learning Core, National Institute of Mental Health, Bethesda, MD, USA
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National Institute of Mental Health
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Machine Learning Core, National Institute of Mental Health, Bethesda, MD, USA
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Humboldt-Universität zu Berlin · Deutsches Zentrum für Psychische Gesundheit
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Department of Psychology, Humboldt-Universität zu Berlin, Berlin, Germany
German Center for Mental Health (DZPG), partner site Berlin-Potsdam, Berlin, Germany
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Amsterdam UMC Location Vrije Universiteit Amsterdam
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Department of Psychiatry, Amsterdam UMC, location VUMC, Amsterdam, The Netherlands
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University of Southern California
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Imaging Genetics Center, Mark and Mary Stevens Neuroimaging and Informatics Institute, Keck School of Medicine, University of Southern California, Marina del Rey, CA, USA
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Department of Psychiatry & Neuroscience Institute, University of Cape Town, Cape Town, South Africa
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Janna Marie Bas‐Hoogendam Aachen Department of Developmental and Educational Psychology Institute of Psychology, Leiden University Department of Psychiatry, Leiden University Medical Center Leiden Institute for Brain and Cognition
Leiden University · Leiden University Medical Center
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Department of Developmental and Educational Psychology, Institute of Psychology, Leiden University, Leiden, The Netherlands
Department of Psychiatry, Leiden University Medical Center, Leiden, The Netherlands
Leiden Institute for Brain and Cognition, Leiden, The Netherlands
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South African Medical Research Council · University of Cape Town
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Department of Psychiatry & Neuroscience Institute, University of Cape Town, Cape Town, South Africa
South African Medical Research Council Unit on Risk & Resilience in Mental Disorders, Department of Psychiatry & Neuroscience Institute, University of Cape Town, Cape Town, South Africa
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Nic JA van der Wee Aachen Department of Psychiatry, Leiden University Medical Center Leiden Institute for Brain and Cognition
Leiden University · Leiden University Medical Center
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Department of Psychiatry, Leiden University Medical Center, Leiden, The Netherlands
Leiden Institute for Brain and Cognition, Leiden, The Netherlands
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The University of Texas Rio Grande Valley · National Institute of Mental Health
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Emotion and Development Branch, National Institute of Mental Health, Bethesda, MD, USA
University of Texas Rio Grande Valley, Brownsville, TX, USA
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National Institute of Mental Health
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Emotion and Development Branch, National Institute of Mental Health, Bethesda, MD, USA
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Virginia Commonwealth University · National Institute of Mental Health
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Division of Child and Adolescent Psychiatry, Department of Psychiatry, Virginia Commonwealth University, Richmond, VA, USA
Emotion and Development Branch, National Institute of Mental Health, Bethesda, MD, USA
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