Symptom Distribution Heterogeneity as a Marker for the Course of Major Depression

Symptom Distribution Heterogeneity as a Marker for the Course of Major Depression | 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 Research Article Symptom Distribution Heterogeneity as a Marker for the Course of Major Depression Shiva Khodadadi, Alina Buschhüter, Sarah Alizadeh, Bita Shariatpanahi, and 24 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7047188/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Major Depressive Disorder (MDD) presents diverse symptom patterns, such as sadness or fatigue, influencing its course and treatment response. Using dynamical systems and network theories, which model depression as interconnected symptoms stabilizing in specific patterns (attractor dynamics), we examined whether symptom structure reflects clinical state stability. We applied four mathematical metrics---Entropy, Variance, Gini-Simpson Index, and Coefficient of Variation---as proxies for symptom structure, independent of overall severity, using cross-sectional data. In two studies (longitudinal cohort, $N=1799$; inpatient sample, $N=255$), we compared Healthy Controls vs.\MDD, acute vs.\remitted, and pre- vs.\post-treatment states. Healthier or improved states showed lower Entropy/Gini-Simpson and higher Variance/Coefficient of Variation, indicating more flexible symptom profiles. These metrics distinguished clinical states with 73% accuracy and achieved 63% generalizability across datasets after calibration. Unlike prior network studies focusing on symptom interactions, our severity-independent markers reveal the ''stickiness'' of depressive states, linking rigid profiles to persistent depression and flexible ones to recovery. This approach offers a scalable tool for personalized MDD interventions using routine clinical data. Major Depressive Disorder (MDD) Symptom Heterogeneity Clinical Course Dynamical Systems Full Text Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted 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-7047188","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":481759723,"identity":"54c7db95-f7c2-4026-b1c2-fcaafca951b2","order_by":0,"name":"Shiva Khodadadi","email":"","orcid":"","institution":"Department of Psychiatry and Psychotherapy, University of Marburg","correspondingAuthor":false,"prefix":"","firstName":"Shiva","middleName":"","lastName":"Khodadadi","suffix":""},{"id":481759724,"identity":"aa8c59ae-940c-4cc3-aad8-5241ac57c53b","order_by":1,"name":"Alina Buschhüter","email":"","orcid":"","institution":"Department of 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