Individual Profiling Across the Psychosis Continuum using Affinity Scores

Individual Profiling Across the Psychosis Continuum using Affinity Scores | 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 Individual Profiling Across the Psychosis Continuum using Affinity Scores Tina Kristensen, Karen Marie Sandø Ambrosen, Louise Birkedal Glenthøj, and 8 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8733172/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 11 You are reading this latest preprint version Abstract Patients with psychotic disorders exhibit a continuum of heterogenous symptoms with both differences and similarities across diagnostic categories and illness stages. Tools that capture this individualized variability are warranted for tailoring personalized treatment. To address this, we employed Affinity Scores as an individual-centric statistical approach that complements diagnostic information by modeling individualized patterns within multivariate data. We included 670 participants aged 18–60: 284 healthy controls [HC], 201 individuals at ultra-high risk [UHR], 128 patients with first-episode psychosis [FEP], and 57 patients with a history of schizophrenia [SCZ]. Clinical, cognitive, and demographic data were standardized, and dimensional Affinity Scores were computed using participant-specific neighborhood graphs, weighting proximal neighbors. Multivariate features were derived by integrating Affinity Scores across domains. We evaluated classification accuracy of diagnostic alignment, tested associations with regional brain volumes, and applied elastic net logistic regression to predict UHR-outcomes after one year (remission and transition to psychosis). Affinity Scores revealed diverse individual profiles across the psychosis continuum. Diagnostic classification accuracies ranged from 0.59–0.85, improving with contextual neighborhood information. Significant associations emerged between Affinity Scores and frontal, temporal, and parietal brain volumes, reflecting both shared and distinct neurobiological patterns. For UHR-individuals, two heterogeneity indices predicted transition (ROC AUC = 0.865, Brier = 0.027) and remission (ROC AUC = 0.813, Brier = 0.045) after one year, indicating increased diversity as prognostically relevant. This proof-of-concept study demonstrates how Affinity Scores capture individual-level heterogeneity, complement diagnostic information and predict clinical outcome, and holds promise as a novel and transparent tool for improved diagnostics and tailored treatment strategies informed by individualized profiles. Health sciences/Diseases/Psychiatric disorders/Schizophrenia Scientific community and society/Scientific community psychosis transdiagnostic individualized medicine precision psychiatry prognostic models Full Text Additional Declarations Yes Dr. Ebdrup is part of the Advisory Board of Eli Lilly Denmark A/S, Janssen-Cilag, Lundbeck Pharma A/S, and Takeda Pharmaceutical Company Ltd; and has received lecture fees from Bristol-Myers Squibb, Boehringer Ingelheim, Otsuka Pharma Scandinavia AB, Eli Lilly Company, and Lundbeck Pharma A/S. Dr. Bojesen received lecture fees from Lundbeck Pharma A/S. Dr. Glenthøj was the head of the Lundbeck Foundation Centre of Excellence for Clinical Intervention and Neuropsychiatric Schizophrenia Research (CINS) from January 2009 to December 2021, which was partially financed by an independent grant from the Lundbeck Foundation based on international review and partially financed by the Mental Health Services in the Capital Region of Denmark, the University of Copenhagen, and other foundations. All grants are the property of the Mental Health Services in the Capital Region of Denmark and administrated by them. She has no other conflicts to disclose. Supplementary Files SupplementsAffinityTranslationalPsychiatry.docx Supplementary Cite Share Download PDF Status: Under Review Version 1 posted Review # 3 received at journal 12 May, 2026 Review # 4 received at journal 07 May, 2026 Reviewer # 4 agreed at journal 24 Apr, 2026 Reviewer # 3 agreed at journal 24 Apr, 2026 Reviewer # 2 agreed at journal 24 Apr, 2026 Reviewer # 1 agreed at journal 24 Apr, 2026 Reviewers invited by journal 24 Apr, 2026 Editor assigned by journal 01 Feb, 2026 Submission checks completed at journal 01 Feb, 2026 First submitted to journal 30 Jan, 2026 Unknown event 30 Jan, 2026 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. 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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-8733172","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":629027481,"identity":"cca58f2e-07ac-4d67-a81a-ab6ca137a79a","order_by":0,"name":"Tina 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She has no other conflicts to disclose.","formattedTitle":"\u003cp\u003eIndividual Profiling Across the Psychosis Continuum using Affinity Scores\u003c/p\u003e","fulltext":[],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"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":"translational-psychiatry","isNatureJournal":false,"hasQc":false,"allowDirectSubmit":false,"externalIdentity":"tp","sideBox":"Learn more about [Translational Psychiatry](http://www.nature.com/tp/)","snPcode":"41398","submissionUrl":"https://mts-tp.nature.com/cgi-bin/main.plex","title":"Translational Psychiatry","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"ejp","reportingPortfolio":"Nature AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"psychosis, transdiagnostic, individualized medicine, precision psychiatry, prognostic models","lastPublishedDoi":"10.21203/rs.3.rs-8733172/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8733172/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003ePatients with psychotic disorders exhibit a continuum of heterogenous symptoms with both differences and similarities across diagnostic categories and illness stages. Tools that capture this individualized variability are warranted for tailoring personalized treatment. To address this, we employed \u003cem\u003eAffinity Scores\u003c/em\u003e as an individual-centric statistical approach that complements diagnostic information by modeling individualized patterns within multivariate data.\u003c/p\u003e \u003cp\u003eWe included 670 participants aged 18\u0026ndash;60: 284 healthy controls [HC], 201 individuals at ultra-high risk [UHR], 128 patients with first-episode psychosis [FEP], and 57 patients with a history of schizophrenia [SCZ]. Clinical, cognitive, and demographic data were standardized, and dimensional Affinity Scores were computed using participant-specific neighborhood graphs, weighting proximal neighbors. Multivariate features were derived by integrating Affinity Scores across domains. We evaluated classification accuracy of diagnostic alignment, tested associations with regional brain volumes, and applied elastic net logistic regression to predict UHR-outcomes after one year (remission and transition to psychosis).\u003c/p\u003e \u003cp\u003eAffinity Scores revealed diverse individual profiles across the psychosis continuum. Diagnostic classification accuracies ranged from 0.59\u0026ndash;0.85, improving with contextual neighborhood information. Significant associations emerged between Affinity Scores and frontal, temporal, and parietal brain volumes, reflecting both shared and distinct neurobiological patterns. For UHR-individuals, two heterogeneity indices predicted transition (ROC AUC\u0026thinsp;=\u0026thinsp;0.865, Brier\u0026thinsp;=\u0026thinsp;0.027) and remission (ROC AUC\u0026thinsp;=\u0026thinsp;0.813, Brier\u0026thinsp;=\u0026thinsp;0.045) after one year, indicating \u003cem\u003eincreased diversity\u003c/em\u003e as prognostically relevant.\u003c/p\u003e \u003cp\u003eThis proof-of-concept study demonstrates how Affinity Scores capture individual-level heterogeneity, complement diagnostic information and predict clinical outcome, and holds promise as a novel and transparent tool for improved diagnostics and tailored treatment strategies informed by individualized profiles.\u003c/p\u003e","manuscriptTitle":"Individual Profiling Across the Psychosis Continuum using Affinity Scores","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-05-05 15:02:31","doi":"10.21203/rs.3.rs-8733172/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"editorInvitedReview","content":"This content is not available.","date":"2026-05-12T15:44:40+00:00","index":3,"fulltext":"This content is not available."},{"type":"editorInvitedReview","content":"This content is not available.","date":"2026-05-07T14:45:32+00:00","index":4,"fulltext":"This content is not available."},{"type":"reviewerAgreed","content":"This content is not available.","date":"2026-04-24T20:46:47+00:00","index":4,"fulltext":"This content is not available."},{"type":"reviewerAgreed","content":"This content is not available.","date":"2026-04-24T19:18:45+00:00","index":3,"fulltext":"This content is not available."},{"type":"reviewerAgreed","content":"This content is not available.","date":"2026-04-24T17:28:35+00:00","index":2,"fulltext":"This content is not available."},{"type":"reviewerAgreed","content":"This content is not available.","date":"2026-04-24T16:32:04+00:00","index":1,"fulltext":"This content is not available."},{"type":"reviewersInvited","content":"","date":"2026-04-24T13:31:45+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-02-01T12:52:52+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2026-02-01T12:52:06+00:00","index":"","fulltext":""},{"type":"submitted","content":"Translational Psychiatry","date":"2026-01-30T16:36:51+00:00","index":"","fulltext":""},{"type":"checksFailed","content":"","date":"2026-01-30T15:03:56+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"translational-psychiatry","isNatureJournal":false,"hasQc":false,"allowDirectSubmit":false,"externalIdentity":"tp","sideBox":"Learn more about [Translational Psychiatry](http://www.nature.com/tp/)","snPcode":"41398","submissionUrl":"https://mts-tp.nature.com/cgi-bin/main.plex","title":"Translational Psychiatry","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"ejp","reportingPortfolio":"Nature AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"934ca5f3-df79-4f62-b47a-ecc99c98c481","owner":[],"postedDate":"May 5th, 2026","published":true,"recentEditorialEvents":[{"type":"editorInvitedReview","content":"This content is not available.","date":"2026-05-12T15:44:40+00:00","index":3,"fulltext":"This content is not available."},{"type":"editorInvitedReview","content":"This content is not available.","date":"2026-05-07T14:45:32+00:00","index":4,"fulltext":"This content is not available."}],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[{"id":67572081,"name":"Health sciences/Diseases/Psychiatric disorders/Schizophrenia"},{"id":67572082,"name":"Scientific community and society/Scientific community"}],"tags":[],"updatedAt":"2026-05-05T15:02:31+00:00","versionOfRecord":[],"versionCreatedAt":"2026-05-05 15:02:31","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8733172","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8733172","identity":"rs-8733172","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}