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Publications

Journal Article Ahead of print 1 citation

PubMed: 42343090 DOI: 10.1038/s41467-026-74153-2

Regional, functional and transcriptomic decoding of multidimensional brain structure alterations in obsessive-compulsive disorder.

Nat Commun

Authors: Leonardo Cardoso Saraiva, João R Sato, Isaac Sebenius, Nadza Dzinalija, Carla Del Río-Torné, Fábio Godinho, Antonio C Lopes, Thomas V Fernandez, Monicke O Lima, Vanessa R Ramos, Ricardo Iglesio, Yoshinari Abe, Pino Alonso, Stephanie H Ameis, Alan Anticevic, Ana Araújo, Paul D Arnold, Srinivas Balachander, Nerisa Banaj, Marcelo C Batistuzzo, Francesco Benedetti, Irene Bollettini, Beatrice Bravi, Brian Brennan, Jan Buitelaar, Miguel Castelo-Branco, Sunah Choi, Ana D Costa, Sara Dallaspezia, Damiaan Denys, Isabel C Duarte, Marco A N Echevarria, Goi Khia Eng, Afonso Fernandes, Jamie D Feusner, Martijn Figee, Sophie M D D Fitzsimmons, Leonardo F Fontenelle, Rachael Grazioplene, Minji Ha, Alejandro Hinojosa, Marcelo Q Hoexter, Chaim Huijser, Hao Hu, Anthony James, Minah Kim, Jun Soo Kwon, Luisa Lazaro, Christine Lochner, Mafalda Machado-Sousa … and 52 other authors

Affiliations

  • Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA.
  • Department of Psychiatry, University of São Paulo, São Paulo, Brazil.
  • Center of Mathematics, Computing and Cognition, Universidade Federal do ABC, Santo André, Brazil.
  • Department of Psychiatry, University of Cambridge, Cambridge, UK.
  • Amsterdam UMC, Vrije Universiteit Amsterdam, Department of Psychiatry, Department of Anatomy & Neurosciences, Amsterdam, The Netherlands.
  • Amsterdam Neuroscience, Compulsivity Impulsivity & Attention, Amsterdam, The Netherlands.
  • Psychiatry and Mental Health Group, Neuroscience Program, Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet de Llobregat, Spain.
  • Department of Clinical Sciences, School of Medicine, University of Barcelona, L'Hospitalet de Llobregat, Spain.
  • Neurosurgery Division, Department of Neurology, Hospital das Clínicas, University of São Paulo Medicine School, São Paulo, SP, Brazil.
  • Department of Psychiatry, University of São Paulo, São Paulo, Brazil.
  • Yale Child Study Center, Yale University, New Haven, CT, USA.
  • Department of Psychiatry, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.
  • Sugimoto Psychiatric Clinic, Kyoto, Japan.
  • Network Center for Biomedical Research on Mental Health (CIBERSAM), Carlos III Health Institute (ISCIII), Madrid, Spain.
  • Cundill Centre for Child and Youth Depression, Margaret and Wallace McCain Centre for Child, Youth and Family Mental Health, Centre for Addiction and Mental Health, Toronto, ON, Canada.
  • Department of Psychiatry, Temerty Faculty of Medicine, University of Toronto, Toronto, ON, Canada.
  • Janssen Research & Development, LLC, a Johnson & Johnson Company, Titusville, NJ, USA.
  • CIBIT, ICNAS, University of Coimbra, Coimbra, Portugal.
  • Faculty of Medicine, University of Coimbra, Coimbra, Portugal.
  • The Mathison Centre for Mental Health Research & Education, Hotchkiss Brain Institute, University of Calgary, Calgary, AB, Canada.
  • Departments of Psychiatry and Medical Genetics, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada.
  • OCD Clinic, Department of Psychiatry, National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore, India.
  • Laboratory of Neuropsychiatry, Department of Clinical Neuroscience and Neurorehabilitation, IRCCS Santa Lucia Foundation, Rome, Italy.
  • Department of Methods and Techniques in Psychology, Pontifical Catholic University, São Paulo, SP, Brazil.
  • Vita-Salute San Raffaele University, Milano, Italy.
  • Psychiatry and Clinical Psychobiology, Division of Neuroscience, IRCCS Ospedale San Raffaele, Milano, Italy.
  • McLean Hospital, Belmont, MA, USA.
  • Harvard Medical School, Boston, MA, USA.
  • Radboudumc, Department of Medical Neuroscience, Nijmegen, The Netherlands.
  • Karakter Child and Adolescent Psychiatry University Centre, Nijmegen, The Netherlands.
  • Department of Brain and Cognitive Sciences, Seoul National University College of Natural Sciences, Seoul, Republic of Korea.
  • Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Braga, Portugal.
  • Clinical Academic Center - Braga, Braga, Portugal.
  • Amsterdam UMC, location University of Amsterdam, Department of Psychiatry, Amsterdam, The Netherlands.
  • Amsterdam Neuroscience, Amsterdam, The Netherlands.
  • ICNAS, University of Coimbra, Coimbra, Portugal.
  • Department of Psychiatry, New York University Grossman School of Medicine, New York, NY, USA.
  • Nathan Kline Institute for Psychiatric Research, Orangeburg, NY, USA.
  • Division of Neurosciences & Clinical Translation, Department of Psychiatry, Temerty Faculty of Medicine, University of Toronto, Toronto, ON, Canada.
  • Centre for Addiction and Mental Health, Toronto, ON, Canada.
  • Department of Women's and Children's Health, Karolinska Institutet, Stockholm, Sweden.
  • Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
  • D'Or Institute for Research and Education (IDOR), Rio de Janeiro, RJ, Brazil.
  • Institute of Psychiatry, Federal University of Rio de Janeiro (IPUB/UFRJ), Rio de Janeiro, RJ, Brazil.
  • Department of Psychiatry, School of Clinical Sciences, Monash University, Clayton, VIC, Australia.
  • Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA.
  • MRI Core Facility, IDIBAPS, Barcelona, Spain.
  • Levvel, Amsterdam, The Netherlands.
  • Amsterdam UMC, Department of Child and Adolescent Psychiatry, Amsterdam, The Netherlands.
  • Department of Psychiatry, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, P.R. China.
  • Department of Psychiatry, University of Oxford, Warneford Hospital, Oxford, OX3 7JX, UK.
  • Department of Psychiatry, Seoul National University College of Medicine, Seoul, Republic of Korea.
  • Department of Neuropsychiatry, Seoul National University Hospital, Seoul, Republic of Korea.
  • Department of Psychiatry, Hanyang University College of Medicine, Seoul, Republic of Korea.
  • Department of Neuropsychiatry, Hanyang University Hospital, Seoul, Republic of Korea.
  • Institute of Human Behavioral Medicine, SNU-MRC, Seoul, Republic of Korea.
  • Department of Child and Adolescent Psychiatry and Psychology, Hospital Clínic, Barcelona, Institut d'Investigacions August Pi i Sunyer (IDIBAPS), Barcelona, Spain.
  • Department of Medicine, University of Barcelona, Barcelona, Spain.
  • SAMRC Unit on Risk & Resilience in Mental Disorders, Department of Psychiatry, Stellenbosch University, Stellenbosch, South Africa.

Abstract

Studies of brain morphology in mental illness often focus on a few neuroimaging phenotypes. Here we present a comprehensive morphological characterization in obsessive-compulsive disorder (OCD) in a large sample (2255 OCD, 2264 controls) using nine cortical and four subcortical phenotypes, including several not previously examined in OCD, among them a subcortical structural similarity network phenotype developed here. Spatially distinct regional alterations emerged across structural phenotypes: cortical curvature alterations in default mode and frontoparietal networks, increased structural similarity network node degree in sensorimotor regions, widespread volume reductions associated with medication use, and localized subcortical shape alterations. In brain-behavior predictive models, curvature phenotypes showed the strongest associations with clinical features. Cortical alterations, especially in structural similarity networks, were associated with specific gene expression patterns, implicating dysregulation of excitatory neurons. RNA-sequencing data from tissue collected during functional neurosurgery revealed that genes downregulated in the dorsolateral prefrontal cortex in OCD contributed to the gene expression patterns linked to cortical alterations. Previously reported differentially expressed genes from postmortem brain studies of OCD also contributed. These findings support the importance of a comprehensive approach to characterizing brain morphology and suggest that cortical curvature and structural similarity alterations reflect key pathophysiological processes in OCD.

MeSH

Genes, Biological Science Disciplines, Brain, Phenotype, Obsessive-Compulsive Disorder, Gene Expression