Predicting alcohol dependence from multi‐site brain structural measures
Human Brain Mapping, vol. 43, pp. 555–565
Abstract
To identify neuroimaging biomarkers of alcohol dependence (AD) from structural magnetic resonance imaging, it may be useful to develop classification models that are explicitly generalizable to unseen sites and populations. This problem was explored in a mega-analysis of previously published datasets from 2,034 AD and comparison participants spanning 27 sites curated by the ENIGMA Addiction Working Group. Data were grouped into a training set used for internal validation including 1,652 participants (692 AD, 24 sites), and a test set used for external validation with 382 participants (146 AD, 3 sites). An exploratory data analysis was first conducted, followed by an evolutionary search based feature selection to site generalizable and high performing subsets of brain measurements. Exploratory data analysis revealed that inclusion of case- and control-only sites led to the inadvertent learning of site-effects. Cross validation methods that do not properly account for site can drastically overestimate results. Evolutionary-based feature selection leveraging leave-one-site-out cross-validation, to combat unintentional learning, identified cortical thickness in the left superior frontal gyrus and right lateral orbitofrontal cortex, cortical surface area in the right transverse temporal gyrus, and left putamen volume as final features. Ridge regression restricted to these features yielded a test-set area under the receiver operating characteristic curve of 0.768. These findings evaluate strategies for handling multi-site data with varied underlying class distributions and identify potential biomarkers for individuals with current AD.
Authors 31
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Sage Hahn corresponding
University of Vermont · University of Vermont Medical Center
Affiliation as printed
Department of Psychiatry University of Vermont College of Medicine Burlington Vermont USA
Department of Psychiatry, University of Vermont College of Medicine, Burlington, Vermont, USA
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University of Vermont · University of Vermont Medical Center
Affiliation as printed
Department of Psychiatry University of Vermont College of Medicine Burlington Vermont USA
Department of Psychiatry, University of Vermont College of Medicine, Burlington, Vermont, USA
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Affiliation as printed
Department of Psychology University of Amsterdam Amsterdam the Netherlands
Department of Psychology, University of Amsterdam, Amsterdam, the Netherlands
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University of Rochester Medicine · University of Rochester
Affiliation as printed
Department of Neuroscience & The Ernest J. Del Monte Institute for Neuroscience University of Rochester School of Medicine and Dentistry Rochester New York USA
Department of Neuroscience & The Ernest J. Del Monte Institute for Neuroscience, University of Rochester School of Medicine and Dentistry, Rochester, New York, USA
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Charité - Universitätsmedizin Berlin
Affiliation as printed
Department of Psychiatry and Psychotherapy Charité—Universitätsmedizin Berlin Berlin Germany
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Affiliation as printed
Melbourne School of Psychological Sciences University of Melbourne Melbourne Australia
Melbourne School of Psychological Sciences, University of Melbourne, Melbourne, Australia
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University of Colorado Boulder
Affiliation as printed
Department of Psychology and Neuroscience University of Colorado Boulder Colorado USA
Department of Psychology and Neuroscience, University of Colorado, Boulder, Colorado, USA
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Heidelberg University · Central Institute of Mental Health
Affiliation as printed
Department of Addictive Behaviour and Addiction Medicine, Central Institute of Mental Health Heidelberg University Mannheim Germany
Department of Addictive Behaviour and Addiction Medicine, Central Institute of Mental Health, Heidelberg University, Mannheim, Germany
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Washington University in St. Louis
Affiliation as printed
Department of Psychiatry Washington University School of Medicine St. Louis Missouri USA
Department of Psychiatry, Washington University School of Medicine, St. Louis, Missouri, USA
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Charité - Universitätsmedizin Berlin
Affiliation as printed
Department of Psychiatry and Psychotherapy Charité—Universitätsmedizin Berlin Berlin Germany
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Affiliation as printed
Department of Psychiatry Yale University School of Medicine New Haven Connecticut USA
Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut, USA
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University of California, Los Angeles
Affiliation as printed
David Geffen School of Medicine University of California at Los Angeles Los Angeles California USA
David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, California, USA
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University of Liverpool · Monash University · Australian Catholic University
Affiliation as printed
Department of Psychological Sciences the University of Liverpool Liverpool UK
Monash Institute of Cognitive and Clinical Neurosciences & School of Psychological Sciences Monash University Melbourne Australia
School of Psychology, Faculty of Health Sciences Australian Catholic University Melbourne Australia
Department of Psychological Sciences, the University of Liverpool, Liverpool, UK
Monash Institute of Cognitive and Clinical Neurosciences & School of Psychological Sciences Monash University Melbourne Australia
School of Psychology, Faculty of Health Sciences, Australian Catholic University, Melbourne, Australia
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Affiliation as printed
Behavioural Science Institute Radboud University Nijmegen the Netherlands
Behavioural Science Institute, Radboud University, Nijmegen, the Netherlands
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National Institute on Alcohol Abuse and Alcoholism
Affiliation as printed
Clinical NeuroImaging Research Core, Division of Intramural Clinical and Biological Research National Institute on Alcohol Abuse and Alcoholism Bethesda Maryland USA
Clinical NeuroImaging Research Core, Division of Intramural Clinical and Biological Research, National Institute on Alcohol Abuse and Alcoholism, Bethesda, Maryland, USA
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University of Vermont · University of Vermont Medical Center
Affiliation as printed
Department of Psychiatry University of Vermont College of Medicine Burlington Vermont USA
Department of Psychiatry, University of Vermont College of Medicine, Burlington, Vermont, USA
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University of California San Diego · VA San Diego Healthcare System · Laureate Institute for Brain Research
Affiliation as printed
Laureate Institute for Brain Research Tulsa Oklahoma USA
VA San Diego Healthcare System and Department of Psychiatry University of California San Diego La Jolla California USA
Laureate Institute for Brain Research, Tulsa, Oklahoma, USA
VA San Diego Healthcare System and Department of Psychiatry, University of California San Diego, La Jolla, California, USA
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The University of Melbourne · Orygen
Affiliation as printed
Centre for Youth Mental Health The University of Melbourne Melbourne Australia
Orygen, The National Centre of Excellence in Youth Mental Health Parkville Australia
Centre for Youth Mental Health, The University of Melbourne, Melbourne, Australia
Orygen, The National Centre of Excellence in Youth Mental Health, Parkville, Australia
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Affiliation as printed
Department of Psychiatry Yale University School of Medicine New Haven Connecticut USA
Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut, USA
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Leiden University · Max Planck Institute for Human Cognitive and Brain Sciences
Affiliation as printed
Department of Neurology Max Planck Institute for Human Cognitive and Brain Sciences Leipzig Germany
Institute of Psychology, Cognitive Psychology Unit & Leiden Institute for Brain and Cognition Leiden University Leiden the Netherlands
Department of Neurology, Max Planck Institute for Human Cognitive and Brain Sciences, Leipzig, Germany
Institute of Psychology, Cognitive Psychology Unit & Leiden Institute for Brain and Cognition Leiden University Leiden the Netherlands
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South African Medical Research Council · University of Cape Town
Affiliation as printed
SA MRC Unit on Risk & Resilience in Mental Disorders, Department of Psychiatry & Neuroscience Institute University of Cape Town Cape Town South Africa
SA MRC Unit on Risk & Resilience in Mental Disorders, Department of Psychiatry & Neuroscience Institute University of Cape Town Cape Town South Africa
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National Institute on Drug Abuse
Affiliation as printed
Neuroimaging Research Branch Intramural Research Program, National Institute on Drug Abuse Baltimore Maryland USA
Neuroimaging Research Branch, Intramural Research Program, National Institute on Drug Abuse, Baltimore, Maryland, USA
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Amsterdam UMC Location University of Amsterdam · Amsterdam University Medical Centers · University of Amsterdam
Affiliation as printed
Department of Psychiatry, Amsterdam UMC, Location AMC University of Amsterdam Amsterdam the Netherlands
Department of Psychiatry, Amsterdam UMC, Location AMC, University of Amsterdam, Amsterdam, the Netherlands
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Amsterdam UMC Location Vrije Universiteit Amsterdam
Affiliation as printed
Department of Psychiatry VU University Medical Center Amsterdam the Netherlands
Department of Psychiatry, VU University Medical Center, Amsterdam, the Netherlands
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Charité - Universitätsmedizin Berlin
Affiliation as printed
Department of Psychiatry and Psychotherapy Charité—Universitätsmedizin Berlin Berlin Germany
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Affiliation as printed
Department of Psychology University of Amsterdam Amsterdam the Netherlands
Department of Psychology, University of Amsterdam, Amsterdam, the Netherlands
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University of California, Los Angeles · The University of Melbourne · Melbourne Health
Affiliation as printed
David Geffen School of Medicine University of California at Los Angeles Los Angeles California USA
Melbourne Neuropsychiatry Centre, Department of Psychiatry The University of Melbourne and Melbourne Health Melbourne Australia
David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, California, USA
Melbourne Neuropsychiatry Centre, Department of Psychiatry, The University of Melbourne and Melbourne Health, Melbourne, Australia
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University of Southern California
Affiliation as printed
Imaging Genetics Center, Stevens Institute for Neuroimaging & Informatics, Keck School of Medicine University of Southern California California USA
Imaging Genetics Center, Stevens Institute for Neuroimaging & Informatics, Keck School of Medicine University of Southern California California USA
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Centre Hospitalier Universitaire Sainte-Justine · Université de Montréal
Affiliation as printed
Department of Psychiatry Université de Montreal, CHU Ste Justine Hospital Montreal Quebec Canada
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University of Vermont · University of Vermont Medical Center
Affiliation as printed
Department of Psychiatry University of Vermont College of Medicine Burlington Vermont USA
Department of Psychiatry, University of Vermont College of Medicine, Burlington, Vermont, USA
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University of Vermont · University of Vermont Medical Center
Affiliation as printed
Department of Psychiatry University of Vermont College of Medicine Burlington Vermont USA
Department of Psychiatry, University of Vermont College of Medicine, Burlington, Vermont, USA
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