White matter diffusion estimates in obsessive-compulsive disorder across 1653 individuals: machine learning findings from the ENIGMA OCD Working Group.

Journal: Molecular psychiatry
PMID: 38326559

Abstract

White matter pathways, typically studied with diffusion tensor imaging (DTI), have been implicated in the neurobiology of obsessive-compulsive disorder (OCD). However, due to limited sample sizes and the predominance of single-site studies, the generalizability of OCD classification based on diffusion white matter estimates remains unclear. Here, we tested classification accuracy using the largest OCD DTI dataset to date, involving 1336 adult participants (690 OCD patients and 646 healthy controls) and 317 pediatric participants (175 OCD patients and 142 healthy controls) from 18 international sites within the ENIGMA OCD Working Group. We used an automatic machine learning pipeline (with feature engineering and selection, and model optimization) and examined the cross-site generalizability of the OCD classification models using leave-one-site-out cross-validation. Our models showed low-to-moderate accuracy in classifying (1) "OCD vs. healthy controls" (Adults, receiver operator characteristic-area under the curve = 57.19 ± 3.47 in the replication set; Children, 59.8 ± 7.39), (2) "unmedicated OCD vs. healthy controls" (Adults, 62.67 ± 3.84; Children, 48.51 ± 10.14), and (3) "medicated OCD vs. unmedicated OCD" (Adults, 76.72 ± 3.97; Children, 72.45 ± 8.87). There was significant site variability in model performance (cross-validated ROC AUC ranges 51.6-79.1 in adults; 35.9-63.2 in children). Machine learning interpretation showed that diffusivity measures of the corpus callosum, internal capsule, and posterior thalamic radiation contributed to the classification of OCD from HC. The classification performance appeared greater than the model trained on grey matter morphometry in the prior ENIGMA OCD study (our study includes subsamples from the morphometry study). Taken together, this study points to the meaningful multivariate patterns of white matter features relevant to the neurobiology of OCD, but with low-to-moderate classification accuracy. The OCD classification performance may be constrained by site variability and medication effects on the white matter integrity, indicating room for improvement for future research.

Authors

  • Bo-Gyeom Kim
    Department of Psychology, College of Social Sciences, Seoul National University, Seoul, Republic of Korea.
  • Gakyung Kim
    Department of Brain and Cognitive Sciences, College of Natural Sciences, Seoul National University, Seoul, Republic of Korea.
  • Yoshinari Abe
    Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Department of Psychiatry, Kyoto City, Japan.
  • Pino Alonso
    Bellvitge Biomedical Research Insitute-IDIBELL, Bellvitge University Hospital, Barcelona, Spain.
  • Stephanie Ameis
    The Margaret and Wallace McCain Centre for Child, Youth & Family Mental Health and Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, ON, Canada.
  • Alan Anticevic
    Department of Psychiatry, Yale University School of Medicine, New Haven, CT, 06510, USA.
  • Paul D Arnold
    The Mathison Centre for Mental Health Research & Education, Hotchkiss Brain Institute, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada.
  • Srinivas Balachander
    OCD clinic, Department of Psychiatry, National Institute of Mental Health And Neurosciences (NIMHANS), Bangalore, India.
  • Nerisa Banaj
    Laboratory of Neuropsychiatry, Santa Lucia Foundation IRCCS, Rome, Italy.
  • Nuria Bargalló
    Center of Image Diagnostic, Hospital Clínic de Barcelona, Barcelona, Spain.
  • Marcelo C Batistuzzo
    Department of Psychiatry, University of São Paulo, Brazil.
  • Francesco Benedetti
    Vita-Salute San Raffaele University, Milan, Italy; Division of Neuroscience, Psychiatry and Clinical Psychobiology, IRCCS San Raffaele Scientific Institute, Milan, Italy.
  • Sara Bertolín
    CIBER of Mental Health (CIBERSAM), Carlos III Health Institute, Madrid, Spain.
  • Jan Carl Beucke
    Department of Psychology, Humboldt-Universitat zu Berlin, Berlin, Germany.
  • Irene Bollettini
    Psychiatry & Clinical Psychobiology, Division of Neuroscience, IRCCS Scientific Institute Ospedale San Raffaele, Milano, Italy.
  • Silvia Brem
    Department of Child and Adolescent Psychiatry and Psychotherapy, University Hospital of Psychiatry Zurich, University of Zurich, Zurich, Switzerland.
  • Brian P Brennan
    Biological Psychiatry Laboratory and Psychiatric Epidemiology Research Program, McLean Hospital, Belmont, Massachusetts; Department of Psychiatry, Harvard Medical School, Boston, Massachusetts. Electronic address: bbrennan@partners.org.
  • Jan K Buitelaar
    Donders Center for Brain, Cognition and Behavior, Radboud University Nijmegen, Nijmegen, the Netherlands; Department for Cognitive Neuroscience, Radboud University Medical Center Nijmegen, Nijmegen, the Netherlands; Karakter Child and Adolescent Psychiatry University Center, Radboud University Medical Center, Nijmegen, The Netherlands.
  • Rosa Calvo
    CIBER of Mental Health (CIBERSAM), Carlos III Health Institute, Madrid, Spain.
  • Miguel Castelo-Branco
    Institute for Nuclear Sciences Applied to Health (ICNAS), and Institute for Biomedical Imaging and Life Sciences (IBILI), Faculty of Medicine, University of Coimbra, Coimbra, Portugal.
  • Yuqi Cheng
    Department of Psychiatry, First Affiliated Hospital of Kunming Medical University, Kunming, China.
  • Ritu Bhusal Chhatkuli
    Research Center for Child Mental Development, Chiba University, Chiba, Japan.
  • Valentina Ciullo
    Laboratory of Neuropsychiatry, Santa Lucia Foundation IRCCS, Rome, Italy.
  • Ana Coelho
    Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Braga, Portugal.
  • Beatriz Couto
    Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Braga, Portugal.
  • Sara Dallaspezia
    Psychiatry & Clinical Psychobiology Unit, Division of Neuroscience, Scientific Institute Ospedale San Raffaele, Milano, Italy.
  • Benjamin A Ely
    Department of Psychiatry and Behavioral Sciences, Albert Einstein College of Medicine, Bronx, NY, USA.
  • Sónia Ferreira
    Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Braga, Portugal.
  • Martine Fontaine
    Columbia University Medical College, Columbia University, New York, NY, USA.
  • Jean-Paul Fouche
    SAMRC Genomics of Brain Disorders Unit, Department of Psychiatry, Cape Town, South Africa.
  • Rachael Grazioplene
    Department of Psychiatry, Yale University School of Medicine, New Haven, CT, 06510, USA.
  • Patricia Gruner
    Department of Psychiatry, Yale University School of Medicine, New Haven, CT, 06510, USA.
  • Kristen Hagen
    Hospital of Molde, Møre og Romsdal Hospital Trust, Molde, Norway.
  • Bjarne Hansen
    Bergen Center for Brain Plasticity, Haukeland University Hospital, Bergen, Norway.
  • Gregory L Hanna
    Department of Psychiatry, University of Michigan Medical School, Ann Arbor, MI, USA.
  • Yoshiyuki Hirano
    Research Center for Child Mental Development, Chiba University, Chiba, Japan.
  • Marcelo Q Höxter
    Departamento e Instituto de Psiquiatria do Hospital das Clinicas, IPQ HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, SP, Brazil.
  • Morgan Hough
    Highfield Unit Oxford, Warneford Hospital, Warneford Lane, Headington, Oxford, Oxfordshire, OX3 7JX, UK.
  • Hao Hu
    Department of Geography and Geographic Information Science, University of Illinois at Urbana-Champaign, Urbana, IL, USA.
  • Chaim Huyser
    Levvel, academic center for child and adolescent care, Amsterdam, The Netherlands.
  • Toshikazu Ikuta
    Department of Communication Sciences and Disorders, University of Mississippi, Oxford, MS, USA.
  • Neda Jahanshad
    Imaging Genetics Center, Mark and Mary Stevens Neuroimaging and Informatics Institute, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
  • Anthony James
    University of Oxford, Oxford, United Kingdom.
  • Fern Jaspers-Fayer
    Department of Psychiatry, University of British Columbia, Vancouver, BC, Canada.
  • Selina Kasprzak
    Amsterdam UMC, Vrije Universteit Amsterdam, Department of Psychiatry, Amsterdam Neuroscience, Amsterdam, The Netherlands.
  • Norbert Kathmann
    Department of Psychology, Humboldt-Universität zu Berlin, Berlin, Germany; Zentrum für Psychotherapie, Humboldt-Universität zu Berlin, Berlin, Germany. Electronic address: kathmann@hu-berlin.de.
  • Christian Kaufmann
    Department of Psychology, Humboldt-Universitat zu Berlin, Berlin, Germany.
  • Minah Kim
    Department of Neuropsychiatry, Seoul National University Hospital, Seoul, South Korea.
  • Kathrin Koch
    TUM-Neuroimaging Center (TUM-NIC) of Klinikum rechts der Isar, Technische Universitat Munchen, München, Germany.
  • Gerd Kvale
    Bergen Center for Brain Plasticity, Haukeland University Hospital, Bergen, Norway.
  • Jun Soo Kwon
    Department of Brain and Cognitive Sciences, Seoul National University College of Natural Sciences, Seoul, South Korea.
  • Luisa Lazaro
    CIBER of Mental Health (CIBERSAM), Carlos III Health Institute, Madrid, Spain.
  • Junhee Lee
    Department of Psychiatry, Seoul St. Mary's Hospital, The Catholic University of Korea, College of Medicine, Seoul, Republic of Korea.
  • Christine Lochner
    US/UCT MRC Unit on Anxiety & Stress Disorders, Department of Psychiatry, University of Stellenbosch, South Africa.
  • Jin Lu
    Computer Science & Engineering Department at the University of Connecticut.
  • Daniela Rodriguez Manrique
    TUM-Neuroimaging Center (TUM-NIC) of Klinikum rechts der Isar, Technische Universitat Munchen, München, Germany.
  • Ignacio Martínez-Zalacaín
    Bellvitge Biomedical Research Insitute-IDIBELL, Bellvitge University Hospital, Barcelona, Spain.
  • Yoshitada Masuda
    Department of Radiology, Chiba University Hospital, Chiba, 260-8677, Japan.
  • Koji Matsumoto
    Japan Automobile Research Institute.
  • Maria Paula Maziero
    LIM 23, Instituto de Psiquiatria, Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo, Sao Paulo, Brazil.
  • Jose M Menchón
    Bellvitge Biomedical Research Insitute-IDIBELL, Bellvitge University Hospital, Barcelona, Spain.
  • Luciano Minuzzi
    3 Department of Psychiatry and Behavioral Neurosciences and St. Joseph's Healthcare Hamilton, Hamilton, Canada .
  • Pedro Silva Moreira
    Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Braga, Portugal.
  • Pedro Morgado
    Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Braga, Portugal.
  • Janardhanan C Narayanaswamy
    OCD clinic, Department of Psychiatry, National Institute of Mental Health And Neurosciences (NIMHANS), Bangalore, India.
  • Jin Narumoto
    Department of Psychiatry, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.
  • Ana E Ortiz
    Department of Child and Adolescent Psychiatry and Psychology, Institute of Neurosciences, Hospital Clínic Universitari, Barcelona, Spain.
  • Junko Ota
    Department of Medical Physics and Engineering, Graduate School of Medicine, Osaka University, 1-7 Yamadaoka, Suita, 565-0871, Japan.
  • Jose C Pariente
    Magnetic Resonance Image Core Facility, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.
  • Chris Perriello
    University of Illinois at Urbana-Champaign, Champaign, IL, USA.
  • Maria Picó-Pérez
    Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Braga, Portugal.
  • Christopher Pittenger
    Department of Psychiatry, Yale University School of Medicine, New Haven, CT, 06510, USA.
  • Sara Poletti
    Vita-Salute San Raffaele University, Milan, Italy; Division of Neuroscience, Psychiatry and Clinical Psychobiology, IRCCS San Raffaele Scientific Institute, Milan, Italy. Electronic address: poletti.sara@hsr.it.
  • Eva Real
    CIBER of Mental Health (CIBERSAM), Carlos III Health Institute, Madrid, Spain.
  • Y C Janardhan Reddy
    OCD clinic, Department of Psychiatry, National Institute of Mental Health And Neurosciences (NIMHANS), Bangalore, India.
  • Daan van Rooij
    Donders Center for Brain, Cognition and Behavior, Radboud University Nijmegen, Nijmegen, the Netherlands; Department for Cognitive Neuroscience, Radboud University Medical Center Nijmegen, Nijmegen, the Netherlands.
  • Yuki Sakai
    Division of Radiology, Department of Medical Technology, Kyushu University Hospital, Fukuoka, Japan.
  • João Ricardo Sato
    Center of Mathematics, Computing and Cognition, Federal University of ABC, São Bernardo do Campo, Brazil; Graduate Program in Neuroscience and Cognition, Federal University of ABC, Santo André, Brazil. Electronic address: joao.sato@ufabc.edu.br.
  • Cinto Segalas
    CIBER of Mental Health (CIBERSAM), Carlos III Health Institute, Madrid, Spain.
  • Roseli G Shavitt
    Departamento de Psiquiatria, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, SP, Brazil.
  • Zonglin Shen
    Department of Psychiatry, First Affiliated Hospital of Kunming Medical University, Kunming, China.
  • Eiji Shimizu
    Department of Cognitive Behavioral Physiology, Chiba University Graduate School of Medicine, 1-8-1 Inohana, Chiba, Chiba, 260-8670, Japan.
  • Venkataram Shivakumar
    National Institute of Mental Health and Neurosciences, Department of Integrative Medicine, Bengaluru, India.
  • Noam Soreni
    Department of Psychiatry and Behavioural Neurosciences, McMaster University, Hamilton, Ontario, Canada.
  • Carles Soriano-Mas
    CIBER of Mental Health (CIBERSAM), Carlos III Health Institute, Madrid, Spain.
  • Nuno Sousa
    Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Braga, Portugal; ICVS-3B's-PT Government Associate Laboratory, Braga, Portugal.
  • Mafalda Machado Sousa
    Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Braga, Portugal.
  • Gianfranco Spalletta
    Laboratory of Neuropsychiatry, Santa Lucia Foundation IRCCS, Rome, Italy.
  • Emily R Stern
    Department of Psychiatry, New York University School of Medicine, New York, NY, USA.
  • S Evelyn Stewart
    Department of Psychiatry, University of British Columbia, Vancouver, BC, Canada.
  • Philip R Szeszko
    Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
  • Rajat Thomas
    Weill-Cornell Medicine Qatar, Education City, Doha, Qatar.
  • Sophia I Thomopoulos
    Imaging Genetics Center, Mark and Mary Stevens Neuroimaging and Informatics Institute, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
  • Daniela Vecchio
    Laboratory of Neuropsychiatry, Santa Lucia Foundation IRCCS, Rome, Italy.
  • Ganesan Venkatasubramanian
    National Institute of Mental Health and Neurosciences, Bangalore, India.
  • Chris Vriend
    Amsterdam UMC, Vrije Universteit Amsterdam, Department of Psychiatry, Amsterdam Neuroscience, Amsterdam, The Netherlands.
  • Susanne Walitza
    Department of Child and Adolescent Psychiatry and Psychotherapy, University Hospital of Psychiatry Zurich, University of Zurich, Zurich, Switzerland.
  • Zhen Wang
    Department of Otolaryngology, Longgang Otolaryngology hospital & Shenzhen Key Laboratory of Otolaryngology, Shenzhen Institute of Otolaryngology, Shenzhen, Guangdong, China.
  • Anri Watanabe
    Department of Psychiatry, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.
  • Lidewij Wolters
    Norwegian University of Science and Technology (NTNU), Faculty of Medicine, Regional Centre for Child and Youth Mental Health and Child Welfare (RKBU Central Norway), Klostergata 46, 7030, Trondheim, Norway.
  • Jian Xu
    Department of Cardiology, Lishui Central Hospital and the Fifth Affiliated Hospital of Wenzhou Medical University, Lishui, China.
  • Kei Yamada
    Department of Radiology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kajii-cho, Kawaramachi Hirokoji Agaru, Kamigyo-ku, Kyoto, Kyoto, 602-8566, Japan.
  • Je-Yeon Yun
    Seoul National University Hospital, Seoul, 03080, Republic of Korea.
  • Mojtaba Zarei
    Institute of Medical Science and Technology, Shahid Beheshti University, Tehran, Iran.
  • Qing Zhao
    Institute of Nephrology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China.
  • Xi Zhu
    Department of Psychiatry, Columbia University Irving Medical Center and New York State Psychiatric Institute, New York, New York.
  • Paul M Thompson
    Imaging Genetics Center, Mark and Mary Stevens Neuroimaging and Informatics Institute, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
  • Willem B Bruin
    Amsterdam Neuroscience, Compulsivity, Impulsivity & Attention program, Amsterdam, The Netherlands.
  • Guido A van Wingen
    Amsterdam UMC, locatie AMC, afd. Psychiatrie en Amsterdam Neuroscience, Amsterdam.
  • Federica Piras
    Laboratory of Neuropsychiatry, Department of Clinical and Neuroscience and Neurorehabilitation, IRCCS Santa Lucia Foundation, Rome, Italy.
  • Fabrizio Piras
    Laboratory of Neuropsychiatry, Santa Lucia Foundation IRCCS, Rome, Italy.
  • Dan J Stein
    MRC Unit on Risk & Resilience to Mental Disorders, Department of Psychiatry and Mental Health, University of Cape Town, Cape Town, South Africa.
  • Odile A van den Heuvel
    Amsterdam UMC, Vrije Universteit Amsterdam, Department of Psychiatry, Amsterdam Neuroscience, Amsterdam, The Netherlands.
  • Helen Blair Simpson
    Columbia University Medical College, Columbia University, New York, NY, USA.
  • Rachel Marsh
    Columbia University Medical College, Columbia University, New York, NY, USA.
  • Jiook Cha
    Department of Psychiatry, Columbia University College of Physicians and Surgeons, New York, New York, USA.

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