Multi-site benchmark classification of major depressive disorder using machine learning on cortical and subcortical measures
Abstract
Machine learning (ML) techniques have gained popularity in the neuroimaging field due to their potential for classifying neuropsychiatric disorders. However, the diagnostic predictive power of the existing algorithms has been limited by small sample sizes, lack of representativeness, data leakage, and/or overfitting. Here, we overcome these limitations with the largest multi-site sample size to date (n=5,356) to provide a generalizable ML classification benchmark of major depressive disorder (MDD). Using brain measures from standardized ENIGMA analysis pipelines in FreeSurfer, we were able to classify MDD vs healthy controls (HC) with around 62% balanced accuracy, but when harmonizing the data using ComBat balanced accuracy dropped to approximately 52%. Similar results were observed in stratified groups according to age of onset, antidepressant use, number of episodes and sex. Future studies incorporating higher dimensional brain imaging/phenotype features, and/or using more advanced machine and deep learning methods may achieve more encouraging prospects.
Authors 65
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Universitätsmedizin Göttingen · University of Göttingen
Affiliation as printed
Laboratory of Systems Neuroscience and Imaging in Psychiatry (SNIP-Lab) , Department of Psychiatry and Psychotherapy , University Medical Center Goettingen (UMG) , Georg-August University , Von-Siebold-Str. 5 , 37075 Goettingen , Germany;
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Affiliation as printed
SoCAT Lab , Department of Psychiatry , School of Medicine , Ege University , Izmir , Turkey;
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Affiliation as printed
Department of Psychiatry & Mental Health , University of Cape Town , Cape Town , South Africa;
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Affiliation as printed
Center for Neuroscience , University of Pittsburgh , Pittsburgh , PA , USA ;
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University Medical Center Groningen
Affiliation as printed
Department of Biomedical Sciences of Cells and Systems , University Medical Center Groningen , University of Groningen , Groningen , the Netherlands;
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Affiliation as printed
Department of Psychiatry , Amsterdam UMC , Vrije Universiteit Amsterdam , Amsterdam Neuroscience , Amsterdam Public Health Research Institute , Amsterdam , The Netherlands ;
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Affiliation as printed
SoCAT Lab , Department of Psychiatry , School of Medicine , Ege University , Izmir , Turkey;
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Affiliation as printed
Melbourne Neuropsychiatry Centre , Department of Psychiatry , The University of Melbourne , Parkville , Victoria , Australia;
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Affiliation as printed
Department of Psychiatry and Psychotherapy , Jena University Hospital , Jena , Germany;
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University of Minnesota · University of Minnesota System
Affiliation as printed
Department of Psychology , University of Minnesota , Minneapolis , MN , USA;
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Affiliation as printed
Department of Psychiatry , Amsterdam UMC , Vrije Universiteit Amsterdam , Amsterdam Neuroscience , Amsterdam Public Health Research Institute , Amsterdam , The Netherlands ;
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University of Minnesota Medical Center
Affiliation as printed
Department of Psychiatry and Behavioral Science , University of Minnesota Medical School , Minneapolis , MN , USA;
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National Institute of Mental Health
Affiliation as printed
Section on the Neurobiology and Treatment of Mood Disorders , National Institute of Mental Health , Bethesda , MD , USA;
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Affiliation as printed
Melbourne Neuropsychiatry Centre , Department of Psychiatry , The University of Melbourne , Parkville , Victoria , Australia;
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Affiliation as printed
Imaging Genetics Center , Mark & Mary Stevens Neuroimaging and Informatics Institute ,
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Affiliation as printed
Department of Biomedical Sciences , Florida Stateu University , Tallahassee FL , USA;
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University of East London · King's College London
Affiliation as printed
Centre for Affective Disorders , Institute of Psychiatry , Psychology and Neuroscience , King's College London , London , UK;
School of Psychology , University of East London , London , UK;
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Affiliation as printed
SA MRC Research Unit on Risk & Resilience in Mental Disorders , Department of Psychiatry & Neuroscience Institute , University of Cape Town , Cape Town , South Africa;
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City, University of London · King's College London
Affiliation as printed
Department of Neuroimaging , Institute of Psychiatry , Psychology and Neuroscience , King's College London , London , UK
Department of Psychology , School of Arts and Social Sciences , City , University of London , London , UK;
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Hospital Mare de Déu de la Mercè
Affiliation as printed
FIDMAG Germanes Hospitalàries Research Foundation , Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM) , Barcelona , Catalonia , Spain
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The University of Melbourne · Orygen Youth Health
Affiliation as printed
Centre for Youth Mental Health , The University of Melbourne , Parkville , VIC , Australia;
Orygen , The National Centre of Excellence in Youth Mental Health , Parkville , VIC , Australia;
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Vita-Salute San Raffaele University · IRCCS Ospedale San Raffaele
Affiliation as printed
Division of Neuroscience , IRCCS San Raffaele Scientific Institute , Milano , Italy;
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Vita-Salute San Raffaele University · IRCCS Ospedale San Raffaele
Affiliation as printed
Division of Neuroscience , IRCCS San Raffaele Scientific Institute , Milano , Italy;
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Affiliation as printed
Departments of Psychiatry and Pediatrics , University of Calgary , Calgary , AB , Canada;
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Universitätsmedizin Greifswald · Universität Greifswald
Affiliation as printed
Department of Psychiatry and Psychotherapy , University Medicine Greifswald , Greifswald , Germany;
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Universitätsmedizin Greifswald
Affiliation as printed
Institute for Community Medicine , University Medicine Greifswald , Greifswald , Germany;
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Affiliation as printed
Department of Psychology , Stanford University , Stanford , CA , USA;
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Affiliation as printed
Center Of Excellence On Mood Disorders , Louis A. Faillace , MD ,
Louis
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National Institutes of Health · National Institute of Mental Health
Affiliation as printed
Experimental Therapeutics and Pathophysiology Branch , National Institute for Mental Health , National Institutes of Health , Bethesda , MD , USA;
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Universitätsmedizin Greifswald · German Center for Neurodegenerative Diseases · Universität Greifswald
Affiliation as printed
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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University of Minnesota Medical Center
Affiliation as printed
Department of Psychiatry and Behavioral Science , University of Minnesota Medical School , Minneapolis , MN , USA;
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Amsterdam University Medical Centers
Affiliation as printed
Amsterdam University Medical Centers , location AMC , Department of Radiology and Nuclear Medicine , Amsterdam , the Netherlands;
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Affiliation as printed
Department of Psychiatry , Amsterdam UMC , Vrije Universiteit Amsterdam , Amsterdam Neuroscience , Amsterdam Public Health Research Institute , Amsterdam , The Netherlands ;
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Affiliation as printed
Queensland Brain Institute , The University of Queensland , Brisbane , QLD , Australia;
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Harvard University · Hospital de Sant Pau
Affiliation as printed
Harvard Medical School , Boston , MA , USA;
Sant Pau Mental Health Research Group , Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau , Barcelona , Catalonia , Spain . CIBERSAM , Madrid , Spain;
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Massachusetts General Hospital
Affiliation as printed
Meditation Research Program , Department of Psychiatry , Massachusetts General Hospital ,
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Leiden University · Amsterdam Neuroscience
Affiliation as printed
Department of Psychiatry , Amsterdam UMC , Vrije Universiteit Amsterdam , Amsterdam Neuroscience , Amsterdam Public Health Research Institute , Amsterdam , The Netherlands ;
Institute of Education & Child Studies , Section Forensic Family & Youth Care , Leiden University , Leiden , The Netherlands;
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Affiliation as printed
Center Of Excellence On Mood Disorders , Louis A. Faillace , MD ,
Louis
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Affiliation as printed
Department of Psychiatry , McGill University , Montreal , Quebec , Canada;
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Affiliation as printed
Imaging Genetics Center , Mark & Mary Stevens Neuroimaging and Informatics Institute ,
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Affiliation as printed
Department of Psychiatry & Mental Health , University of Cape Town , Cape Town , South Africa;
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Affiliation as printed
Center for Medical Imaging and Visualization , Linköping University , Linköping , Sweden;
Center for Social and Affective Neuroscience , Department of Biomedical and Clinical Sciences , Linköping University , Linköping , Sweden;
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Universitätsmedizin Greifswald · Universität Greifswald
Affiliation as printed
Institute for Radiology and Neuroradiology , University Medicine Greifswald , Greifswald , Germany;
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Affiliation as printed
Centre for Youth Mental Health , The University of Melbourne , Parkville , VIC , Australia;
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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 , VIC , Australia;
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Affiliation as printed
Imaging Genetics Center , Mark & Mary Stevens Neuroimaging and Informatics Institute ,
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Affiliation as printed
Department of Psychiatry & Mental Health , University of Cape Town , Cape Town , South Africa;
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King's College London · Cardiff University
Affiliation as printed
Cardiff University Brain Research Imaging Center , Cardiff University , Cardiff , UK;
Department of Neuroimaging , Institute of Psychiatry , Psychology and Neuroscience , King's College London , London , UK
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University of California, Los Angeles · University of California, San Francisco
Affiliation as printed
Department of Psychiatry and Behavioral Sciences , Division of Child and Adolescent Psychiatry , Weill Institute for Neurosciences , University of California , San Francisco , San Francisco , CA , USA;
Department of Psychology , University of California , Los Angeles , Los Angeles , CA , USA;
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University of California, San Francisco
Affiliation as printed
Department of Psychiatry and Behavioral Sciences , Division of Child and Adolescent Psychiatry , Weill Institute for Neurosciences , University of California , San Francisco , San Francisco , CA , USA;
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University of Minnesota Medical Center
Affiliation as printed
Department of Psychiatry and Behavioral Science , University of Minnesota Medical School , Minneapolis , MN , USA;
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Affiliation as printed
Department of Psychiatry , Amsterdam UMC , Vrije Universiteit Amsterdam , Amsterdam Neuroscience , Amsterdam Public Health Research Institute , Amsterdam , The Netherlands ;
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Affiliation as printed
Orygen , The National Centre of Excellence in Youth Mental Health , Parkville , VIC , Australia;
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Affiliation as printed
Imaging Genetics Center , Mark & Mary Stevens Neuroimaging and Informatics Institute ,
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Universitätsmedizin Göttingen · University of Göttingen
Affiliation as printed
Laboratory of Systems Neuroscience and Imaging in Psychiatry (SNIP-Lab) , Department of Psychiatry and Psychotherapy , University Medical Center Goettingen (UMG) , Georg-August University , Von-Siebold-Str. 5 , 37075 Goettingen , Germany;
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