Neuroimaging-based classification of PTSD using data-driven computational approaches: A multisite big data study from the ENIGMA-PGC PTSD consortium
NeuroImage, vol. 283, pp. 120412
Abstract
BACKGROUND: Recent advances in data-driven computational approaches have been helpful in devising tools to objectively diagnose psychiatric disorders. However, current machine learning studies limited to small homogeneous samples, different methodologies, and different imaging collection protocols, limit the ability to directly compare and generalize their results. Here we aimed to classify individuals with PTSD versus controls and assess the generalizability using a large heterogeneous brain datasets from the ENIGMA-PGC PTSD Working group. METHODS: We analyzed brain MRI data from 3,477 structural-MRI; 2,495 resting state-fMRI; and 1,952 diffusion-MRI. First, we identified the brain features that best distinguish individuals with PTSD from controls 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 in each modality (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: These results have the potential to provide a baseline classification performance for PTSD when using large scale neuroimaging datasets. Our findings show that the control group used can heavily affect classification performance. The DVAE framework provided better generalizability for the multi-site data. This may be more significant in clinical practice since the neuroimaging-based diagnostic DVAE classification models are much less site-specific, rendering them more generalizable.
Authors 97
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Columbia University Irving Medical Center · New York State Psychiatric Institute · Columbia University
Affiliation as printed
Department of Psychiatry, Columbia University Medical Center, New York, NY, USA; New York State Psychiatric Institute, New York, NY, USA
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
Affiliation as printed
New York State Psychiatric Institute, New York, NY, USA
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New York State Psychiatric Institute
Affiliation as printed
New York State Psychiatric Institute, New York, NY, USA
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Columbia University Irving Medical Center · Columbia University
Affiliation as printed
Department of Psychiatry, Columbia University Medical Center, New York, NY, USA
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Affiliation as printed
University of Rochester, Rochester, NY, USA
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Affiliation as printed
University of Haifa, Haifa, Israel
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Affiliation as printed
Tel-Aviv University, Tel Aviv, Israel
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Columbia University Irving Medical Center · New York State Psychiatric Institute · Columbia University
Affiliation as printed
Department of Psychiatry, Columbia University Medical Center, New York, NY, USA; New York State Psychiatric Institute, New York, NY, USA
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
Affiliation as printed
Baylor College of Medicine, Houston, TX, USA; Yale University School of Medicine, New Haven, CT, USA
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
Affiliation as printed
Baylor College of Medicine, Houston, TX, USA; Yale University School of Medicine, New Haven, CT, USA
Baylor College of Medicine, Houston, TX, USA
Yale University School of Medicine, New Haven, CT, USA
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Affiliation as printed
Duke University, Durham, NC, USA
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Affiliation as printed
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
Affiliation as printed
Center for Trauma Recovery, Department of Psychological Sciences, University of Missouri-St. Louis, St. Louis, MO, USA
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Affiliation as printed
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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Affiliation as printed
University of Toledo, Toledo, OH, USA
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Affiliation as printed
University of Groningen, Groningen, The Netherlands
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McLean Hospital · Minneapolis VA Health Care System
Affiliation as printed
Minneapolis VA Health Care System, Minneapolis, MN, USA
Division of Women's Mental Health, McLean Hospital, Belmont, MA, USA
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University of Wisconsin–Madison · McLean Hospital · Ministry of Defence
Affiliation as printed
University of Wisconsin-Madison, Madison, WI, USA
Brain Research and Innovation Centre, Ministry of Defence, Utrecht, The Netherlands
af Cognitive and Clinical Neuroimaging Core, McLean Hospital, Belmont, MA, USA
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Affiliation as printed
Duke University, Durham, NC, USA
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University of Utah · McLean Hospital
Affiliation as printed
University of Utah School of Medicine, Salt Lake City, UT, USA
Division of Women's Mental Health, McLean Hospital, Belmont, MA, USA
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Western University · University of British Columbia, Okanagan Campus
Affiliation as printed
Departments of Psychology and Psychiatry, Neuroscience Program, Western University, London, ON, 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; Department of Psychology,
University of British Columbia, Okanagan, Kelowna, British Columbia, Canada
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Affiliation as printed
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 · Washington University in St. Louis · Imaging, Brain, and Neuropsychiatry · Centre Hospitalier Universitaire de Tours · Stanford University
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UMR 1253, CIC 1415, University of Tours, CHRU de Tours, INSERM, France
Department of Radiology, Washington University School of Medicine, St. Louis, MO, USA
y Stanford University, Stanford, CA, USA
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Tel Aviv University · Stanford University
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Stanford University, Stanford, CA, USA
Tel-Aviv University, Tel Aviv, Israel
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Emory University · McLean Hospital
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Emory University Department of Psychiatry and Behavioral Sciences, Atlanta, GA, USA
Division of Women's Mental Health, McLean Hospital, Belmont, MA, USA
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Federal Aviation Administration · Civil Aerospace Medical Institute · University of Otago
Affiliation as printed
Civil Aerospace Medical Institute, US Federal Aviation Administration, Oklahoma City, OK, USA
Brain Health Research Centre, Department of Anatomy, University of Otago, Dunedin, New Zealand
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Affiliation as printed
Marquette University, Milwaukee, WI, USA
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Affiliation as printed
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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McLean Hospital · Ministry of Defence
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Brain Research and Innovation Centre, Ministry of Defence, Utrecht, The Netherlands
af Cognitive and Clinical Neuroimaging Core, McLean Hospital, Belmont, MA, USA
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McLean Hospital · UNSW Sydney · New York State Psychiatric Institute
Affiliation as printed
Cognitive and Clinical Neuroimaging Core, McLean Hospital, Belmont, MA, USA
School of Psychology, University of New South Wales, Sydney, NSW, Australia
New York State Psychiatric Institute, Unit 69, 1051 Riverside Drive, New York, NY 10032, USA
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Washington University in St. Louis · University of Otago
Affiliation as printed
Department of Radiology, Washington University School of Medicine, St. Louis, MO, USA
Brain Health Research Centre, Department of Anatomy, University of Otago, Dunedin, New Zealand
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McLean Hospital · UNSW Sydney · New York State Psychiatric Institute
Affiliation as printed
Cognitive and Clinical Neuroimaging Core, McLean Hospital, Belmont, MA, USA
School of Psychology, University of New South Wales, Sydney, NSW, Australia
New York State Psychiatric Institute, Unit 69, 1051 Riverside Drive, New York, NY 10032, USA
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University of Wisconsin–Madison
Affiliation as printed
University of Wisconsin-Madison, Madison, WI, USA
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Affiliation as printed
Division of Neuroradiology, Brigham and Women's Hospital, Boston, MA, USA
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Affiliation as printed
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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Affiliation as printed
Heidelberg University, Heidelberg, Germany
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University of Cape Town · University of Münster · Ghent University · University of Illinois Chicago
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University of Münster, Münster, Germany
al University of Illinois at Chicago, Chicago, IL, USA
am Ghent University, Ghent, Belgium
an University of Cape Town, Cape Town, South Africa
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University of Cape Town · University of Münster · Ghent University · University of Illinois Chicago
Affiliation as printed
University of Illinois at Chicago, Chicago, IL, USA
University of Münster, Münster, Germany
al University of Illinois at Chicago, Chicago, IL, USA
am Ghent University, Ghent, Belgium
an University of Cape Town, Cape Town, South Africa
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UNSW Sydney · Ghent University · New York State Psychiatric Institute
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Ghent University, Ghent, Belgium
School of Psychology, University of New South Wales, Sydney, NSW, Australia
New York State Psychiatric Institute, Unit 69, 1051 Riverside Drive, New York, NY 10032, USA
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Affiliation as printed
Duke University, Durham, NC, USA
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University of Cape Town · UNSW Sydney · New York State Psychiatric Institute
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University of Cape Town, Cape Town, South Africa
School of Psychology, University of New South Wales, Sydney, NSW, Australia
New York State Psychiatric Institute, Unit 69, 1051 Riverside Drive, New York, NY 10032, USA
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University of Southern California · Brigham and Women's Hospital · Amsterdam UMC Location University of Amsterdam · Amsterdam University Medical Centers · University of Amsterdam
Affiliation as printed
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
Department of Psychiatry, Amsterdam University Medical Centers, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
Division of Neuroradiology, Brigham and Women's Hospital, Boston, MA, USA
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Baylor University · McLean Hospital
Affiliation as printed
Department of Psychology and Neuroscience, Baylor University, Waco, TX, USA
Division of Women's Mental Health, McLean Hospital, Belmont, MA, USA
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Affiliation as printed
Wayne State University School of Medicine, Detroit, MI, USA
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Affiliation as printed
Division of Women's Mental Health, McLean Hospital, Belmont, MA, USA
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McLean Hospital · Ministry of Defence
Affiliation as printed
Brain Research and Innovation Centre, Ministry of Defence, Utrecht, The Netherlands
af Cognitive and Clinical Neuroimaging Core, McLean Hospital, Belmont, MA, USA
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Affiliation as printed
University of Michigan, Ann Arbor, MI, USA
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Brigham and Women's Hospital · Ludwig-Maximilians-Universität München
Affiliation as printed
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
Affiliation as printed
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
Affiliation as printed
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 · UNSW Sydney · New York State Psychiatric Institute
Affiliation as printed
University of Cape Town, Cape Town, South Africa
School of Psychology, University of New South Wales, Sydney, NSW, Australia
New York State Psychiatric Institute, Unit 69, 1051 Riverside Drive, New York, NY 10032, USA
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University of Southern California · McLean Hospital · Westmead Institute for Medical Research
Affiliation as printed
Westmead Institute for Medical Research, Westmead, NSW, Australia
Division of Women's Mental Health, McLean Hospital, Belmont, MA, USA
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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Affiliation as printed
Yale University School of Medicine, New Haven, CT, USA
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Western University · UNSW Sydney · New York State Psychiatric Institute
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Department of Neuroscience, Western University, London, ON, Canada
School of Psychology, University of New South Wales, Sydney, NSW, Australia
New York State Psychiatric Institute, Unit 69, 1051 Riverside Drive, New York, NY 10032, USA
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McLean Hospital · University of Wisconsin–Milwaukee
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University of Wisconsin-Milwaukee, Milwaukee, WI, USA
Division of Women's Mental Health, McLean Hospital, Belmont, MA, USA
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Harvard University · McLean Hospital · UNSW Sydney · New York State Psychiatric Institute
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McLean Hospital, Belmont, MA, USA; Harvard Medical School, Boston, MA, USA
School of Psychology, University of New South Wales, Sydney, NSW, Australia
New York State Psychiatric Institute, Unit 69, 1051 Riverside Drive, New York, NY 10032, USA
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Chinese Academy of Sciences · McLean Hospital · Ministry of Defence · Institute of Psychology, Chinese Academy of Sciences
Affiliation as printed
Institute of Psychology, Chinese Academy of Sciences, Beijing, China
Brain Research and Innovation Centre, Ministry of Defence, Utrecht, The Netherlands
af Cognitive and Clinical Neuroimaging Core, McLean Hospital, Belmont, MA, USA
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Texas A&M Health Science Center · UNSW Sydney · New York State Psychiatric Institute · Texas A&M University
Affiliation as printed
Psychiatry and Behavioral Science, Texas A&M University Health Science Center, College Station, TX, USA
School of Psychology, University of New South Wales, Sydney, NSW, Australia
New York State Psychiatric Institute, Unit 69, 1051 Riverside Drive, New York, NY 10032, USA
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Jiangsu University · Nanjing General Hospital of Nanjing Military Command · Nanjing University
Affiliation as printed
Department of Medical Imaging, Jinling Hospital, Medical School of Nanjing University, Nanjing, Jiangsu, China
Department of Radiology, The Affiliated Yixing Hospital of Jiangsu University, Yixing, Jiangsu, China
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Affiliation as printed
Department of Radiology, The Affiliated Yixing Hospital of Jiangsu University, Yixing, Jiangsu, China
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University of Iowa · Washington University in St. Louis
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University of Iowa, Iowa City, IA, USA
Department of Radiology, Washington University School of Medicine, St. Louis, MO, USA
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UNSW Sydney · New York State Psychiatric Institute · Charité - Universitätsmedizin Berlin
Affiliation as printed
Charité Universitätsmedizin Berlin Campus Charite Mitte: Charite Universitatsmedizin Berlin, Berlin, Germany
School of Psychology, University of New South Wales, Sydney, NSW, Australia
New York State Psychiatric Institute, Unit 69, 1051 Riverside Drive, New York, NY 10032, USA
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Baylor College of Medicine · Yale University · Stanford University
Affiliation as printed
Stanford University, Stanford, CA, USA
Baylor College of Medicine, Houston, TX, USA
Yale University School of Medicine, New Haven, CT, USA
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University of Southern California · McLean Hospital · VA Heart of Texas Health Care Network
Affiliation as printed
VISN 17 Center of Excellence for Research on Returning War Veterans, Waco, TX, USA
Division of Women's Mental Health, McLean Hospital, Belmont, MA, USA
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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Harvard University · UNSW Sydney · New York State Psychiatric Institute
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Harvard University, Boston, MA, USA
School of Psychology, University of New South Wales, Sydney, NSW, Australia
New York State Psychiatric Institute, Unit 69, 1051 Riverside Drive, New York, NY 10032, USA
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UNSW Sydney · Ghent University · New York State Psychiatric Institute
Affiliation as printed
Ghent University, Ghent, Belgium
School of Psychology, University of New South Wales, Sydney, NSW, Australia
New York State Psychiatric Institute, Unit 69, 1051 Riverside Drive, New York, NY 10032, USA
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UNSW Sydney · Amsterdam University Medical Centers · New York State Psychiatric Institute · Vrije Universiteit Amsterdam · Amsterdam UMC Location Vrije Universiteit Amsterdam
Affiliation as printed
Department of Psychiatry, Amsterdam University Medical Centers, VU University Medical Center, VU University, Amsterdam, The Netherlands
School of Psychology, University of New South Wales, Sydney, NSW, Australia
New York State Psychiatric Institute, Unit 69, 1051 Riverside Drive, New York, NY 10032, USA
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Western University · University of British Columbia, Okanagan Campus · University of Otago
Affiliation as printed
Departments of Psychology and Psychiatry, Neuroscience Program, Western University, London, ON, Canada; Department of Psychology, University of British Columbia, Okanagan, Kelowna, British Columbia, Canada
Brain Health Research Centre, Department of Anatomy, University of Otago, Dunedin, New Zealand
Departments of Psychology and Psychiatry, Neuroscience Program, Western University, London, ON, Canada; Department of Psychology,
University of British Columbia, Okanagan, Kelowna, British Columbia, Canada
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University of Wisconsin–Madison
Affiliation as printed
University of Wisconsin-Madison, Madison, WI, USA
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McLean Hospital · University of Toledo
Affiliation as printed
University of Toledo, Toledo, OH, USA
Division of Women's Mental Health, McLean Hospital, Belmont, MA, USA
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Vanderbilt University · UNSW Sydney · New York State Psychiatric Institute
Affiliation as printed
Department of Psychology, Vanderbilt University, Nashville, TN, USA
School of Psychology, University of New South Wales, Sydney, NSW, Australia
New York State Psychiatric Institute, Unit 69, 1051 Riverside Drive, New York, NY 10032, 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 University Medical Centers, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
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University of Washington · UNSW Sydney · New York State Psychiatric Institute
Affiliation as printed
University of Washington, Seattle, WA, USA
School of Psychology, University of New South Wales, Sydney, NSW, Australia
New York State Psychiatric Institute, Unit 69, 1051 Riverside Drive, New York, NY 10032, USA
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UNSW Sydney · New York State Psychiatric Institute · The Ohio State University
Affiliation as printed
Department of Psychiatry and Behavioral Health, Ohio State University, Columbus, OH, USA
School of Psychology, University of New South Wales, Sydney, NSW, Australia
New York State Psychiatric Institute, Unit 69, 1051 Riverside Drive, New York, NY 10032, USA
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Nanjing General Hospital of Nanjing Military Command · UNSW Sydney · New York State Psychiatric Institute · Nanjing University
Affiliation as printed
Department of Medical Imaging, Jinling Hospital, Medical School of Nanjing University, Nanjing, Jiangsu, China
School of Psychology, University of New South Wales, Sydney, NSW, Australia
New York State Psychiatric Institute, Unit 69, 1051 Riverside Drive, New York, NY 10032, USA
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UNSW Sydney · Neuroscience Research Australia
Affiliation as printed
School of Psychology, University of New South Wales, Sydney, NSW, Australia; Neuroscience Research Australia, Randwick, NSW, Australia
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Masaryk University · UNSW Sydney · New York State Psychiatric Institute
Affiliation as printed
Masaryk University, Brno, Czechia
School of Psychology, University of New South Wales, Sydney, NSW, Australia
New York State Psychiatric Institute, Unit 69, 1051 Riverside Drive, New York, NY 10032, USA
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Harvard University · McLean Hospital · UNSW Sydney · New York State Psychiatric Institute
Affiliation as printed
McLean Hospital, Belmont, MA, USA; Harvard Medical School, Boston, MA, USA
School of Psychology, University of New South Wales, Sydney, NSW, Australia
New York State Psychiatric Institute, Unit 69, 1051 Riverside Drive, New York, NY 10032, USA
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Masaryk University · McLean Hospital
Affiliation as printed
Masaryk University, Brno, Czechia
Division of Women's Mental Health, McLean Hospital, Belmont, MA, USA
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Marquette University · Northwestern University
Affiliation as printed
Northwestern Neighborhood and Networks Initiative, Northwestern University Institute for Policy Research, Evanston, IL, USA
Marquette University, Milwaukee, WI, USA
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Harvard University · McLean Hospital · UNSW Sydney · New York State Psychiatric Institute
Affiliation as printed
McLean Hospital, Belmont, MA, USA; Harvard Medical School, Boston, MA, USA
School of Psychology, University of New South Wales, Sydney, NSW, Australia
New York State Psychiatric Institute, Unit 69, 1051 Riverside Drive, New York, NY 10032, USA
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University of Southern California
Affiliation as printed
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 · UNSW Sydney · New York State Psychiatric Institute
Affiliation as printed
University of Washington, Seattle, WA, USA
School of Psychology, University of New South Wales, Sydney, NSW, Australia
New York State Psychiatric Institute, Unit 69, 1051 Riverside Drive, New York, NY 10032, USA
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Brigham and Women's Hospital · Heidelberg University · McLean Hospital
Affiliation as printed
Heidelberg University, Heidelberg, Germany
Division of Neuroradiology, Brigham and Women's Hospital, Boston, MA, USA
Division of Women's Mental Health, McLean Hospital, Belmont, MA, USA
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Brigham and Women's Hospital · McLean Hospital
Affiliation as printed
Psychiatry Neuroimaging Laboratory, Brigham and Women's Hospital, Boston, MA, USA
Division of Women's Mental Health, McLean Hospital, Belmont, MA, USA
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University of North Carolina at Chapel Hill · Brigham and Women's Hospital · McLean Hospital
Affiliation as printed
University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
Division of Neuroradiology, Brigham and Women's Hospital, Boston, MA, USA
Division of Women's Mental Health, McLean Hospital, Belmont, MA, USA
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University of Southern California · University of Toledo
Affiliation as printed
University of Toledo, Toledo, OH, USA
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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Affiliation as printed
Heidelberg University, Heidelberg, Germany
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UNSW Sydney · New York State Psychiatric Institute · Charité - Universitätsmedizin Berlin
Affiliation as printed
Charité Universitätsmedizin Berlin Campus Charite Mitte: Charite Universitatsmedizin Berlin, Berlin, Germany
School of Psychology, University of New South Wales, Sydney, NSW, Australia
New York State Psychiatric Institute, Unit 69, 1051 Riverside Drive, New York, NY 10032, USA
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UNSW Sydney · VA San Diego Healthcare System · New York State Psychiatric Institute · Center of Excellence for Stress and Mental Health
Affiliation as printed
Center of Excellence for Stress and Mental Health, VA San Diego Healthcare System, San Diego, CA, USA
School of Psychology, University of New South Wales, Sydney, NSW, Australia
New York State Psychiatric Institute, Unit 69, 1051 Riverside Drive, New York, NY 10032, USA
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