Classification of major depressive disorder using vertex-wise brain sulcal depth, curvature, and thickness with a deep and a shallow learning model.

Journal: Molecular psychiatry
Published Date: Oct 3, 2025

Abstract

Major depressive disorder (MDD) is a complex psychiatric disorder that affects the lives of hundreds of millions of individuals around the globe. Even today, researchers debate if morphological alterations in the brain are linked to MDD, likely due to the heterogeneity of this disorder. The application of deep learning tools to neuroimaging data, capable of capturing complex non-linear patterns, has the potential to provide diagnostic and predictive biomarkers for MDD. However, previous attempts to demarcate MDD patients and healthy controls (HC) based on segmented cortical features via linear machine learning approaches have reported low accuracies. In this study, we used globally representative data from the ENIGMA-MDD working group containing 7012 participants from 31 sites (N = 2772 MDD and N = 4240 HC), which allows a comprehensive analysis with generalizable results. Based on the hypothesis that integration of vertex-wise cortical features can improve classification performance, we evaluated the classification of a DenseNet and a Support Vector Machine (SVM), with the expectation that the former would outperform the latter. As we analyzed a multi-site sample, we additionally applied the ComBat harmonization tool to remove potential nuisance effects of site. We found that both classifiers exhibited close to chance performance (balanced accuracy DenseNet: 51%; SVM: 53%), when estimated on unseen sites. Slightly higher classification performance (balanced accuracy DenseNet: 58%; SVM: 55%) was found when the cross-validation folds contained subjects from all sites, indicating site effect. In conclusion, the integration of vertex-wise morphometric features and the use of the non-linear classifier did not lead to the differentiability between MDD and HC. Our results support the notion that MDD classification on this combination of features and classifiers is unfeasible. Future studies are needed to determine whether more sophisticated integration of information from other MRI modalities such as fMRI and DWI will lead to a higher performance in this diagnostic task.

Authors

  • Roberto Goya-Maldonado
    Laboratory of Systems Neuroscience and Imaging in Psychiatry (SNIP-Lab), Department of Psychiatry and Psychotherapy, University Medical Center Göttingen (UMG), Göttingen, Germany.
  • Tracy Erwin-Grabner
    Laboratory of Systems Neuroscience and Imaging in Psychiatry (SNIP-Lab), Department of Psychiatry and Psychotherapy, University Medical Center Göttingen (UMG), Georg-August University, Göttingen, Germany.
  • Ling-Li Zeng
    College of Mechatronics and Automation, National University of Defense Technology, Changsha, China.
  • Christopher R K Ching
    Imaging Genetics Center, Stevens Institute for Neuroimaging and Informatics, University of Southern California, Marina Del Rey, CA, USA.
  • André Aleman
    Interdisciplinary Center Psychopathology and Emotion regulation (ICPE), Neuroimaging Center (BCN-NIC), University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
  • Alyssa R Amod
    Department of Psychiatry & Mental Health, Neuroscience Institute, University of Cape Town, Cape Town, South Africa.
  • Zeynep Başgöze
    University of Minnesota, Minneapolis, Minnesota, USA.
  • Francesco Benedetti
    Vita-Salute San Raffaele University, Milan, Italy; Division of Neuroscience, Psychiatry and Clinical Psychobiology, IRCCS San Raffaele Scientific Institute, Milan, Italy.
  • Bianca Besteher
    Department of Psychiatry and Psychotherapy, Jena University Hospital, Philosophenweg 3, 07743 Jena, Germany. Electronic address: [email protected].
  • Katharina Brosch
    Department of Psychiatry and Psychotherapy, University of Marburg, Germany; Center for Mind, Brain and Behavior (CMBB), University of Marburg, Germany.
  • Robin Bülow
    Institute of Diagnostic Radiology and Neuroradiology, University of Greifswald, Germany.
  • Romain Colle
    MOODS Team, INSERM 1018, Centre de Recherche en Epidémiologie et Santé Des Populations, Université Paris-Saclay, Faculté de Médecine Paris-Saclay, Le Kremlin Bicêtre, Le Kremlin-Bicêtre, France.
  • Colm G Connolly
    Department of Psychiatry and the Langley Porter Psychiatric Institute, Division of Child and Adolescent Psychiatry, Weill Institute for Neurosciences, University of California, San Francisco, 401 Parnassus Avenue, San Francisco, CA 94143, USA; Department of Biomedical Sciences, Florida State University College of Medicine, 1115 West Call Street, Tallahassee, FL 32306, USA.
  • Emmanuelle Corruble
    MOODS Team, INSERM 1018, Centre de Recherche en Epidémiologie et Santé Des Populations, Université Paris-Saclay, Faculté de Médecine Paris-Saclay, Le Kremlin Bicêtre, Le Kremlin-Bicêtre, France.
  • Baptiste Couvy-Duchesne
    Institute for Molecular Bioscience, the University of Queensland, St Lucia, Queensland, Australia.
  • Kathryn Cullen
  • Udo Dannlowski
    Department of Psychiatry and Psychotherapy, University of Münster, Germany.
  • Christopher G Davey
    Department of Psychiatry, The University of Melbourne, Melbourne, Australia.
  • Annemiek Dols
    Department of Psychiatry, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam Neuroscience, Amsterdam Public Health Research Institute, Amsterdam, the Netherlands.
  • Jan Ernsting
    Institute for Translational Psychiatry, University of Münster, Münster, Germany.
  • Jennifer W Evans
    Experimental Therapeutics and Pathophysiology Branch, National Institute for Mental Health, National Institutes of Health, Bethesda, MD, USA.
  • Lukas Fisch
    Institute for Translational Psychiatry, University of Münster, Münster, Germany.
  • Paola Fuentes-Claramonte
    FIDMAG Germanes Hospitalaries Research Foundation, Barcelona, Spain.
  • Ali Saffet Gönul
    Department of Psychiatry, Ege University, Bornova, Izmir, Turkey. Electronic address: [email protected].
  • Ian H Gotlib
    Department of Psychology, Stanford University, Stanford, CA, USA.
  • Hans J Grabe
    Department of Psychiatry and Psychotherapy, University Medicine Greifswald, Germany.
  • Nynke A Groenewold
    Department of Psychiatry & Mental Health, Neuroscience Institute, University of Cape Town, Cape Town, South Africa.
  • Dominik Grotegerd
    Department of Psychiatry and Psychotherapy, University of Münster, Germany.
  • Tim Hahn
  • J Paul Hamilton
    Center for Social and Affective Neuroscience, Department of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden.
  • Laura K M Han
    Department of Psychiatry, Amsterdam University Medical Centers, Vrije Universiteit and GGZ inGeest, Amsterdam Neuroscience, Amsterdam, The Netherlands.
  • Ben J Harrison
    Department of Psychiatry, The University of Melbourne, Melbourne, Australia.
  • Tiffany C Ho
    Department of Psychiatry and Behavioral Sciences, Division of Child and Adolescent Psychiatry, Weill Institute for Neurosciences, University of California, San Francisco, CA, 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.
  • Alec J Jamieson
    Department of Psychiatry, The University of Melbourne, Melbourne, Australia.
  • Andriana Karuk
    FIDMAG Germanes Hospitalàries Research Foundation, Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Instituto de Salud Carlos III, Barcelona, Catalonia, Spain.
  • Tilo Kircher
    Department of Psychiatry, University of Marburg, Marburg, Germany.
  • Bonnie Klimes-Dougan
  • Sheri-Michelle Koopowitz
    Department of Psychiatry & Mental Health, Neuroscience Institute, University of Cape Town, Cape Town, South Africa.
  • Thomas Lancaster
    Cardiff University Brain Research Imaging Centre, Cardiff University, Cardiff, UK.
  • Ramona Leenings
    Institute for Translational Psychiatry, University of Münster, Münster, Germany.
  • Meng Li
    Co-Innovation Center for the Sustainable Forestry in Southern China; Cerasus Research Center; College of Biology and the Environment, Nanjing Forestry University, Nanjing, China.
  • David E J Linden
    Cardiff University Brain Research Imaging Centre, Cardiff University, Cardiff, UK.
  • Frank P MacMaster
    Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, Canada.
  • David M A Mehler
    Institute for Translational Psychiatry, University of Münster, Münster, Germany.
  • Susanne Meinert
    Institute for Translational Psychiatry, University of Münster, Germany; Institute for Translational Neuroscience, University of Münster, Germany.
  • Elisa Melloni
    Division of Neuroscience, IRCCS Scientific Institute Ospedale San Raffaele, Milano, Italy.
  • Bryon A Mueller
    University of Minnesota, Minneapolis, Minnesota, USA.
  • Benson Mwangi
    Department of Psychiatry and Behavioral Sciences, Center of Excellence on Mood Disorders, Medical School, University of Texas Health Science Center at Houston, USA. Electronic address: [email protected].
  • Igor Nenadić
    Department of Psychiatry and Psychotherapy, Jena University Hospital, Jena, Germany; Department of Psychiatry and Psychotherapy, Philipps University Marburg & Marburg University Hospital UKGM, Marburg, Germany. Electronic address: [email protected].
  • Amar Ojha
    Center for Neuroscience, University of Pittsburgh, Pittsburgh, PA, USA.
  • Yasumasa Okamoto
    Department of Psychiatry and Neurosciences. Graduate School of Biomedical & Health Sciences, Hiroshima University, Hiroshima, Japan.
  • Mardien L Oudega
    Department of Psychiatry, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam Neuroscience, Amsterdam Public Health Research Institute, Amsterdam, the Netherlands.
  • Brenda W J H Penninx
    Department of Psychiatry and Amsterdam Neuroscience, Amsterdam UMC, Vrije Universiteit, Amsterdam, The Netherlands.
  • 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: [email protected].
  • Edith Pomarol-Clotet
    FIDMAG Germanes Hospitalaries Research Foundation, Barcelona, Spain.
  • Maria J Portella
    Sant Pau Mental Health Research Group, Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau, Barcelona, Catalonia, Spain.
  • Joaquim Radua
    FIDMAG Germanes Hospitalaries Research Foundation, Barcelona, Spain.
  • Elena Rodríguez-Cano
    FIDMAG Germanes Hospitalàries Research Foundation, Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Instituto de Salud Carlos III, Barcelona, Catalonia, Spain.
  • Matthew D Sacchet
    Department of Psychology, Stanford University, Stanford, CA, USA.
  • Raymond Salvador
    FIDMAG Germanes Hospitalaries Research Foundation, Barcelona, Spain.
  • Anouk Schrantee
    Amsterdam UMC, Department of Radiology and Nuclear Medicine, University of Amsterdam, Amsterdam, the Netherlands.
  • Kang Sim
    Research Division, Institute of Mental Health, Singapore, 10 Buangkok View, Singapore, 539747, Singapore. [email protected].
  • Jair C Soares
    University of Texas Health Science Center at Houston, Houston, TX, USA.
  • Aleix Solanes
    FIDMAG - Germanes Hospitalaries, Barcelona, Spain.
  • 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.
  • Frederike Stein
    Department of Psychiatry and Psychotherapy, University of Marburg, Germany; Center for Mind, Brain and Behavior (CMBB), University of Marburg, Germany.
  • Aleks Stolicyn
    Division of Psychiatry, Centre for Clinical Brain Sciences, University of Edinburgh, Scotland, UK.
  • 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.
  • Yara J Toenders
    Centre for Youth Mental Health, the University of Melbourne, Parkville, VIC, Australia.
  • Aslihan Uyar-Demir
    SoCAT Lab, Department of Psychiatry, School of Medicine, Ege University, Izmir, Turkey.
  • Eduard Vieta
    CIBER Salud Mental (CIBERSAM), Madrid, Spain.
  • Yolanda Vives-Gilabert
    Intelligent Data Analysis Laboratory (IDAL), Department of Electronic Engineering, Universitat de València, Valencia, Spain.
  • Henry Völzke
    Institute for Community Medicine, University Medicine Greifswald, Greifswald, Germany.
  • Martin Walter
    Clinical Affective Neuroimaging Laboratory, Leibniz Institute for Neurobiology, Magdeburg, Germany.
  • Heather C Whalley
    Division of Psychiatry, University of Edinburgh, Edinburgh, UK.
  • Sarah Whittle
    Melbourne Neuropsychiatry Centre, Department of Psychiatry, the University of Melbourne, Parkville, VIC, Australia.
  • Nils Winter
    Institute for Translational Psychiatry, University of Münster, Germany.
  • Katharina Wittfeld
    Department of Psychiatry and Psychotherapy, University Medicine Greifswald, Germany.
  • Margaret J Wright
    Queensland Brain Institute, the University of Queensland, Brisbane, QLD, Australia.
  • Mon-Ju Wu
    University of Texas Health Science Center at Houston, Houston, TX, USA.
  • Tony T Yang
    Department of Psychiatry and the Langley Porter Psychiatric Institute, Division of Child and Adolescent Psychiatry, Weill Institute for Neurosciences, University of California, San Francisco, 401 Parnassus Avenue, San Francisco, CA 94143, USA.
  • Carlos Zarate
    Section on the Neurobiology and Treatment of Mood Disorders, National Institute of Mental Health, Bethesda, MD, USA.
  • Dick J Veltman
    Department of Psychiatry, Amsterdam UMC location Vrije Universiteit Amsterdam, Amsterdam, the Netherlands.
  • Lianne Schmaal
    Orygen, The National Centre of Excellence in Youth Mental Health, Melbourne, Australia.
  • 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.

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