Multimodal Imaging-Based Classification of PTSD Using Data-Driven Computational Approaches: A Multisite Big Data Study from the ENIGMA-PGC PTSD Consortium
bioRxiv (Cold Spring Harbor Laboratory)
Abstract
Abstract Background Current clinical assessments of Posttraumatic stress disorder (PTSD) rely solely on subjective symptoms and experiences reported by the patient, rather than objective biomarkers of the illness. Recent advances in data-driven computational approaches have been helpful in devising tools to objectively diagnose psychiatric disorders. Here we aimed to classify individuals with PTSD versus controls using heterogeneous brain datasets from the ENIGMA-PGC PTSD Working group. Methods We analyzed brain MRI data from 3,527 structural-MRI; 2,502 resting state-fMRI; and 1,953 diffusion-MRI. First, we identified the brain features that best distinguish individuals with PTSD from controls (TEHC and HC) using traditional machine learning methods. Second, we assessed the utility of the denoising variational autoencoder (DVAE) and evaluated its classification performance. Third, we assessed the generalizability and reproducibility of both models using leave-one-site-out cross-validation procedure for each modality. Results We found lower performance in classifying PTSD vs. controls with data from over 20 sites (60% test AUC for s-MRI, 59% for rs-fMRI and 56% for d-MRI), as compared to other studies run on single-site data. The performance increased when classifying PTSD from HC without trauma history across all three modalities (75% AUC). The classification performance remained intact when applying the DVAE framework, which reduced the number of features. Finally, we found that the DVAE framework achieved better generalization to unseen datasets compared with the traditional machine learning frameworks, albeit performance was slightly above chance. Conclusion Our findings highlight the promise offered by machine learning methods for the diagnosis of patients with PTSD. The utility of brain biomarkers across three MRI modalities and the contribution of DVAE models for improving generalizability offers new insights into neural mechanisms involved in PTSD. Significance ⍰ Classifying PTSD from trauma-unexposed healthy controls (HC) using three imaging modalities performed well (∼75% AUC), but performance suffered markedly when classifying PTSD from trauma-exposed healthy controls (TEHC) using three imaging modalities (∼60% AUC). ⍰ Using deep learning for feature reduction (denoising variational auto-encoder; DVAE) dramatically reduced the number of features with no concomitant performance degradation. ⍰ Utilizing denoising variational autoencoder (DVAE) models improves generalizability across heterogeneous multi-site data compared with the traditional machine learning frameworks
Authors 97
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Xi Zhu corresponding
Columbia University Irving Medical Center · New York State Psychiatric Institute · Columbia University
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Department of Psychiatry, Columbia University Medical Center, New York, NY, USA
New York State Psychiatric Institute, New York, NY, USA
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New York State Psychiatric Institute
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New York State Psychiatric Institute, New York, NY, USA
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New York State Psychiatric Institute
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New York State Psychiatric Institute, New York, NY, USA
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Columbia University Irving Medical Center · Columbia University
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Department of Psychiatry, Columbia University Medical Center, New York, NY, USA
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University of Rochester, Rochester, NY, USA
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University of Haifa, Haifa, Israel
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Tel-Aviv University, Tel Aviv, Israel
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Columbia University Irving Medical Center · New York State Psychiatric Institute · Columbia University
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Department of Psychiatry, Columbia University Medical Center, New York, NY, USA
New York State Psychiatric Institute, New York, NY, USA
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Baylor College of Medicine · Yale University
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Baylor College of Medicine, Houston, TX, USA
Yale University School of Medicine, New Haven, CT, USA
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Baylor College of Medicine · Yale University
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Baylor College of Medicine, Houston, TX, USA
Yale University School of Medicine, New Haven, CT, USA
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Duke University, Durham, NC, USA
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Sanford School of Medicine, University of South Dakota, Vermillion, SD, USA
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University of Nebraska Medical Center
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Munroe-Meyer Institute, University of Nebraska Medical Center, Omaha, NE, USA
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University of California San Diego
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University of California San Diego, La Jolla, CA, USA
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University of Missouri–St. Louis
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Center for Trauma Recovery, Department of Psychological Sciences, University of Missouri-St. Louis, St. Louis, MO, USA
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School of Psychology, University of New South Wales, Sydney, NSW, Australia
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University of California San Diego
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University of California San Diego, La Jolla, CA, USA
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The University of Texas at Austin
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Department of Psychiatry, University of Texas at Austin, Austin, TX, USA
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University of Toledo, Toledo, OH, USA
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University of Groningen, Groningen, The Netherlands
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Minneapolis VA Health Care System
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Minneapolis VA Health Care System, Minneapolis, MN, USA
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University of Wisconsin–Madison
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University of Wisconsin-Madison, Madison, WI, USA
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Duke University, Durham, NC, USA
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University of Utah School of Medicine, Salt Lake City, UT, USA
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Western University · University of British Columbia, Okanagan Campus
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Departments of Psychology and Psychiatry, Neuroscience Program, Western University, London, ON, Canada; Department of Psychology, University of British Columbia, Okanagan, Kelowna, British Columbia, Canada
Department of Psychology, University of British Columbia, Okanagan, Kelowna, British Columbia, Canada
Departments of Psychology and Psychiatry, Neuroscience Program, Western University, London, ON, Canada
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Medical College of Wisconsin, Milwaukee, WI, USA
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Minneapolis VA Health Care System
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Minneapolis VA Health Care System, Minneapolis, MN, USA
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Université de Tours · Inserm · Imaging, Brain, and Neuropsychiatry · Centre Hospitalier Universitaire de Tours
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UMR 1253, CIC 1415, University of Tours, CHRU de Tours, INSERM, France
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Stanford University, Stanford, CA, USA
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Emory University Department of Psychiatry and Behavioral Sciences, Atlanta, GA, USA
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Federal Aviation Administration · Civil Aerospace Medical Institute
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Civil Aerospace Medical Institute, US Federal Aviation Administration, Oklahoma City, OK, USA
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Marquette University, Milwaukee, WI, USA
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Brain Health Research Centre, Department of Anatomy, University of Otago, Dunedin, New Zealand
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Amsterdam UMC Location University of Amsterdam · Amsterdam University Medical Centers · University of Amsterdam
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Department of Psychiatry, Amsterdam University Medical Centers, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
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Brain Research and Innovation Centre, Ministry of Defence, Utrecht, The Netherlands
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Cognitive and Clinical Neuroimaging Core, McLean Hospital, Belmont, MA, USA
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Washington University in St. Louis
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Department of Radiology, Washington University School of Medicine, St. Louis, MO, USA
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Cognitive and Clinical Neuroimaging Core, McLean Hospital, Belmont, MA, USA
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University of Wisconsin–Madison
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University of Wisconsin-Madison, Madison, WI, USA
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Division of Neuroradiology, Brigham and Women’s Hospital, Boston, MA, USA
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Duke University, Durham, NC, USA
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University of Wisconsin–Madison
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School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, USA
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Heidelberg University, Heidelberg, Germany
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University of Münster, Münster, Germany
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University of Illinois Chicago
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University of Illinois at Chicago, Chicago, IL, USA
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Ghent University, Ghent, Belgium
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Duke University, Durham, NC, USA
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University of Cape Town, Cape Town, South Africa
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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 of the University of Southern California, Marina del Rey, CA, USA
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Department of Psychology and Neuroscience, Baylor University, Waco, TX, USA
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Wayne State University School of Medicine, Detroit, MI, USA
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Division of Women’s Mental Health, McLean Hospital, Belmont, MA, USA
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Brain Research and Innovation Centre, Ministry of Defence, Utrecht, The Netherlands
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University of Michigan, Ann Arbor, MI, USA
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Brigham and Women's Hospital · Ludwig-Maximilians-Universität München
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Department of Child and Adolescent Psychiatry, Psychosomatic and Psychotherapy, Ludwig Maximilian University of Munich, Munich, Germany
Psychiatry Neuroimaging Laboratory, Brigham and Women’s Hospital, Boston, MA, USA
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Radboud University Nijmegen · Donders Centre for Cognitive Neuroimaging · Donders Institute for Brain, Cognition and Behaviour
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Donders Institute for Brain, Cognition and Behavior, Centre for Cognitive Neuroimaging, Radboud University Nijmegen, Nijmegen, The Netherlands
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Brigham and Women's Hospital · Ludwig-Maximilians-Universität München
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Department of Child and Adolescent Psychiatry, Psychosomatic and Psychotherapy, Ludwig Maximilian University of Munich, Munich, Germany
Psychiatry Neuroimaging Laboratory, Brigham and Women’s Hospital, Boston, MA, USA
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University of Cape Town, Cape Town, South Africa
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Westmead Institute for Medical Research
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Westmead Institute for Medical Research, Westmead, NSW, Australia
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Yale University School of Medicine, New Haven, CT, USA
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Department of Neuroscience, Western University, London, ON, Canada
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University of Wisconsin–Milwaukee
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University of Wisconsin-Milwaukee, Milwaukee, WI, USA
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Harvard University · McLean Hospital
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Harvard Medical School, Boston, MA, USA
McLean Hospital, Belmont, MA, USA
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Chinese Academy of Sciences · Institute of Psychology, Chinese Academy of Sciences
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Institute of Psychology, Chinese Academy of Sciences, Beijing, China
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Texas A&M Health Science Center · Texas A&M University
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Psychiatry and Behavioral Science, Texas A&M University Health Science Center, College Station, TX, USA
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Nanjing General Hospital of Nanjing Military Command · Nanjing University
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Department of Medical Imaging, Jinling Hospital, Medical School of Nanjing University, Nanjing, Jiangsu, China
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Department of Radiology, The Affiliated Yixing Hospital of Jiangsu University, Yixing, Jiangsu, China
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University of Iowa, Iowa City, IA, USA
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Charité - Universitätsmedizin Berlin
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Charité Universitätsmedizin Berlin Campus Charite Mitte: Charite Universitatsmedizin Berlin, Berlin, Germany
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Stanford University, Stanford, CA, USA
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VA Heart of Texas Health Care Network
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VISN 17 Center of Excellence for Research on Returning War Veterans, Waco, TX, USA
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Harvard University, Boston, MA, USA
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Ghent University, Ghent, Belgium
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Amsterdam University Medical Centers · Vrije Universiteit Amsterdam · Amsterdam UMC Location Vrije Universiteit Amsterdam
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Department of Psychiatry, Amsterdam University Medical Centers, VU University Medical Center, VU University, Amsterdam, The Netherlands
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Western University · University of British Columbia, Okanagan Campus
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Departments of Psychology and Psychiatry, Neuroscience Program, Western University, London, ON, Canada; Department of Psychology, University of British Columbia, Okanagan, Kelowna, British Columbia, Canada
Department of Psychology, University of British Columbia, Okanagan, Kelowna, British Columbia, Canada
Departments of Psychology and Psychiatry, Neuroscience Program, Western University, London, ON, Canada
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University of Wisconsin–Madison
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University of Wisconsin-Madison, Madison, WI, USA
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University of Toledo, Toledo, OH, USA
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Department of Psychology, Vanderbilt University, Nashville, TN, USA
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Amsterdam UMC Location University of Amsterdam · Amsterdam University Medical Centers · University of Amsterdam
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Department of Psychiatry, Amsterdam University Medical Centers, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
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University of Washington, Seattle, WA, USA
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Department of Psychiatry and Behavioral Health, Ohio State University, Columbus, OH, USA
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Nanjing General Hospital of Nanjing Military Command · Nanjing University
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Department of Medical Imaging, Jinling Hospital, Medical School of Nanjing University, Nanjing, Jiangsu, China
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UNSW Sydney · Neuroscience Research Australia
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Neuroscience Research Australia, Randwick, NSW, Australia
School of Psychology, University of New South Wales, Sydney, NSW, Australia
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Masaryk University, Brno, Czechia
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Harvard University · McLean Hospital
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Harvard Medical School, Boston, MA, USA
McLean Hospital, Belmont, MA, USA
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Masaryk University, Brno, Czechia
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Northwestern Neighborhood and Networks Initiative, Northwestern University Institute for Policy Research, Evanston, IL, USA
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Harvard University · McLean Hospital
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Harvard Medical School, Boston, MA, USA
McLean Hospital, Belmont, MA, 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 of the University of Southern California, Marina del Rey, CA, USA
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University of Washington, Seattle, WA, USA
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Heidelberg University, Heidelberg, Germany
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Psychiatry Neuroimaging Laboratory, Brigham and Women’s Hospital, Boston, MA, USA
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University of North Carolina at Chapel Hill
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University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
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University of Toledo, Toledo, OH, USA
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Heidelberg University, Heidelberg, Germany
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Charité - Universitätsmedizin Berlin
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Charité Universitätsmedizin Berlin Campus Charite Mitte: Charite Universitatsmedizin Berlin, Berlin, Germany
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VA San Diego Healthcare System · Center of Excellence for Stress and Mental Health
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Center of Excellence for Stress and Mental Health, VA San Diego Healthcare System, San Diego, CA, USA