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

Regional, functional and transcriptomic decoding of multidimensional brain structure alterations in obsessive-compulsive disorder | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Regional, functional and transcriptomic decoding of multidimensional brain structure alterations in obsessive-compulsive disorder Leonardo Cardoso Saraiva, João Sato, Isaac Sebenius, Nadza Dzinalija, and 123 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6900305/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted You are reading this latest preprint version Abstract Studies of brain morphology in mental illness often incompletely characterize structural variation, focusing on a few neuroimaging phenotypes. Here we present a comprehensive morphological characterization in obsessive-compulsive disorder (OCD) using nine cortical and four subcortical phenotypes in a large sample (2255 OCD, 2264 controls). Spatially distinct patterns emerged across structural phenotypes, with cortical curvature alterations affecting default mode and frontoparietal networks, changes in structural similarity networks impacting sensorimotor regions, and widespread volume reductions associated with medication use. 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. Transcriptomic data from tissue collected during neurosurgery revealed that genes downregulated in dorsolateral prefrontal cortex in OCD were involved in expression patterns linked to cortical alterations. 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. Biological sciences/Neuroscience/Computational neuroscience Biological sciences/Computational biology and bioinformatics/Machine learning Biological sciences/Genetics/Gene expression Health sciences/Diseases/Psychiatric disorders Full Text Additional Declarations Yes there is potential Competing Interest. Alan Anticevic is founder, president, and board member of Manifest Technologies. Pino Alonso has received funding from Boston Scientific, Johnson & Johnson, Casen Recordati, and Viatris as a lecturer and to attend medical conferences. Jan K. Buitelaar has, in the past 3 years, served as consultant, advisory-board member, and/or speaker for Takeda, Roche, Medice, Angelini, Neuraxpharm, and Servier; he is not an employee or shareholder of any of these companies and reports no other financial or material support, including expert testimony, patents, or royalties. Jamie D. Feusner receives consultation fees from NOCD, Inc. Pedro Morgado has, in the past 3 years, received grants, CME-related honoraria, or consulting fees from Angelini, AstraZeneca, Bial, Biogen, DGS-Portugal, CES, FCT, FLAD, Janssen-Cilag, Gulbenkian Foundation, Lundbeck, Springer Healthcare, Tecnimede, Viatris, and 2CA-Braga. David Mataix-Cols receives royalties for articles contributed to UpToDate, Inc., and is part-owner of Scandinavian E-Health AB (all outside the submitted work). Yuki Sakai is an employee of XNef, Inc. Dan J. Stein has, in the past 3 years, received consultancy honoraria from Discovery Vitality, Johnson & Johnson, Kanna, L’Oréal, Lundbeck, Orion, Sanofi, Servier, Takeda, and Vistagen. Christopher Pittenger has, in the past 3 years, consulted for Biohaven Pharmaceuticals, Ceruvia Lifesciences, Freedom Biosciences, UCB BioPharma, Nobilis Therapeutics, Transcend Therapeutics, F-Prime Capital Partners, Madison Avenue Partners, and Lundbeck Therapeutics; received research support from Transcend, Freedom, and Biohaven; and holds equity in Alco Therapeutics, Biohaven Pharmaceuticals, and Mind Therapeutics, none of which relate to the current work, and is an inventor on several unrelated patents. Supplementary Files ExtendedData.xlsx Extended Data SupplementaryInformation.docx Supplementary Information Cite Share Download PDF Status: Under Review Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-6900305","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":476262248,"identity":"41b65490-ec5e-4fd4-b9de-c39e7edaf936","order_by":0,"name":"Leonardo Cardoso 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Pino Alonso has received funding from Boston Scientific, Johnson \u0026 Johnson, Casen Recordati, and Viatris as a lecturer and to attend medical conferences. Jan K. Buitelaar has, in the past 3 years, served as consultant, advisory-board member, and/or speaker for Takeda, Roche, Medice, Angelini, Neuraxpharm, and Servier; he is not an employee or shareholder of any of these companies and reports no other financial or material support, including expert testimony, patents, or royalties. Jamie D. Feusner receives consultation fees from NOCD, Inc. Pedro Morgado has, in the past 3 years, received grants, CME-related honoraria, or consulting fees from Angelini, AstraZeneca, Bial, Biogen, DGS-Portugal, CES, FCT, FLAD, Janssen-Cilag, Gulbenkian Foundation, Lundbeck, Springer Healthcare, Tecnimede, Viatris, and 2CA-Braga. David Mataix-Cols receives royalties for articles contributed to UpToDate, Inc., and is part-owner of Scandinavian E-Health AB (all outside the submitted work). Yuki Sakai is an employee of XNef, Inc. Dan J. Stein has, in the past 3 years, received consultancy honoraria from Discovery Vitality, Johnson \u0026 Johnson, Kanna, L’Oréal, Lundbeck, Orion, Sanofi, Servier, Takeda, and Vistagen. Christopher Pittenger has, in the past 3 years, consulted for Biohaven Pharmaceuticals, Ceruvia Lifesciences, Freedom Biosciences, UCB BioPharma, Nobilis Therapeutics, Transcend Therapeutics, F-Prime Capital Partners, Madison Avenue Partners, and Lundbeck Therapeutics; received research support from Transcend, Freedom, and Biohaven; and holds equity in Alco Therapeutics, Biohaven Pharmaceuticals, and Mind Therapeutics, none of which relate to the current work, and is an inventor on several unrelated patents.","formattedTitle":"Regional, functional and transcriptomic decoding of multidimensional brain structure alterations in obsessive-compulsive disorder","fulltext":[],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":true,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":true,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"nature-portfolio","isNatureJournal":true,"hasQc":false,"allowDirectSubmit":false,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"","title":"Nature Portfolio","twitterHandle":"","acdcEnabled":false,"dfaEnabled":false,"editorialSystem":"ejp","reportingPortfolio":"","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"","lastPublishedDoi":"10.21203/rs.3.rs-6900305/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6900305/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"Studies of brain morphology in mental illness often incompletely characterize structural variation, focusing on a few neuroimaging phenotypes. Here we present a comprehensive morphological characterization in obsessive-compulsive disorder (OCD) using nine cortical and four subcortical phenotypes in a large sample (2255 OCD, 2264 controls). Spatially distinct patterns emerged across structural phenotypes, with cortical curvature alterations affecting default mode and frontoparietal networks, changes in structural similarity networks impacting sensorimotor regions, and widespread volume reductions associated with medication use. 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. Transcriptomic data from tissue collected during neurosurgery revealed that genes downregulated in dorsolateral prefrontal cortex in OCD were involved in expression patterns linked to cortical alterations. 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.","manuscriptTitle":"Regional, functional and transcriptomic decoding of multidimensional brain structure alterations in obsessive-compulsive disorder","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-06-26 06:42:58","doi":"10.21203/rs.3.rs-6900305/v1","editorialEvents":[],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"nature-communications","isNatureJournal":true,"hasQc":false,"allowDirectSubmit":false,"externalIdentity":"NCOMMS","sideBox":"Learn more about [Nature Communications](http://www.nature.com/ncomms/)","snPcode":"","submissionUrl":"https://mts-ncomms.nature.com/","title":"Nature Communications","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"ejp","reportingPortfolio":"Nature Communications","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"107438cc-3263-4f7f-9fd7-2cb2f1a91b8a","owner":[],"postedDate":"June 26th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[{"id":50573739,"name":"Biological sciences/Neuroscience/Computational neuroscience"},{"id":50573740,"name":"Biological sciences/Computational biology and bioinformatics/Machine learning"},{"id":50573741,"name":"Biological sciences/Genetics/Gene expression"},{"id":50573742,"name":"Health sciences/Diseases/Psychiatric disorders"}],"tags":[],"updatedAt":"2026-01-05T20:10:17+00:00","versionOfRecord":[],"versionCreatedAt":"2025-06-26 06:42:58","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-6900305","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6900305","identity":"rs-6900305","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}