Predicting Alcohol Dependence from Multi-Site Brain Structural Measures
Abstract
Abstract Background The search for neuroimaging biomarkers of alcohol use disorder (AUD) has primarily been restricted to significance testing in small datasets of low diversity. To identify neurobiological markers beyond individual differences, it may be useful to develop classification models for AUD. The ever-increasing quantity of neuroimaging data demands methods that are robust to the complexities of multi-site designs and are generalizable to data from new scanners. Methods This study represents a mega-analysis of previously published datasets from 2,034 AUD and comparison participants spanning 27 sites, coordinated by the ENIGMA Addiction Working Group. Data were grouped into a training set including 1,652 participants (692 AUD, 24 sites), and test set with 382 participants (146 AUD, 3 sites). A battery of machine learning classifiers was evaluated using repeated random cross-validation (CV) and leave-site-out CV. Area under the receiver operating characteristic curve (AUC) was our base metric of performance. Results Multi-objective evolutionary search was conducted to identify sparse, generalizable, and high performing subsets of brain measurements. 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, appeared most frequently across searches. Restricting a regularized logistic regression model to these four features yielded a test-set AUC of .768. Conclusions Developing classification models on multi-site data with varied underlying class distributions poses unique challenges. Supplementing datasets with controls from new sites and performing feature selection increases generalizability. Four features identified by evolutionary search may serve as specific biomarkers for individuals with current AUD.
Authors 26
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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
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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
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Affiliation as printed
Departments 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 NY, USA
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Affiliation as printed
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, Boulder, USA
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Washington University in St. Louis
Affiliation as printed
Department of Psychiatry, Washington University School of Medicine, St. Louis MO, 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, 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
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Affiliation as printed
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 MD, 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
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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 OK, USA
VA San Diego Healthcare System and Department of Psychiatry, University of California San Diego, La Jolla, 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
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Affiliation as printed
Department of Psychiatry, Yale University School of Medicine, New Haven CT, USA
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Zsuzsika Sjoerds Aachen Institute of Psychology Cognitive Psychology Unit & Leiden Institute for Brain and Cognition
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
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Affiliation as printed
SA MRC Unit on Risk & Resilience in Mental Disorders, Dept 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, MD, USA
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Amsterdam UMC Location University of Amsterdam · University of Amsterdam
Affiliation as printed
Department of Psychiatry, AmsterdamUMC, 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
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Affiliation as printed
Departments of Psychology, University of Amsterdam, Amsterdam, the Netherlands
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The University of Melbourne · Melbourne Health · Monash University
Affiliation as printed
Melbourne Neuropsychiatry Centre, Department of Psychiatry, The University of Melbourne and Melbourne Health, Melbourne, Australia
Monash Institute of Cognitive and Clinical Neurosciences & School of Psychological Sciences, Monash University, 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, Marina del Rey, CA, 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 QC, 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
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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
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