NEGR1 can influence symptom severity in fluoxetine treated major depression disorder patients

Circulating NEGR1 Protein Levels Associate with Symptom Severity in Drug-Naïve Major Depressive 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 Research Article Circulating NEGR1 Protein Levels Associate with Symptom Severity in Drug-Naïve Major Depressive Disorder Burcu Bayoglu, Gulseren Akdeniz, Nese Kocabasoglu, Cana Aksoy Poyraz, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4421084/v3 This work is licensed under a CC BY 4.0 License Status: Posted Version 3 posted You are reading this latest preprint version Show more versions Abstract Background: Neuronal growth regulator 1 (NEGR1) is a cell adhesion molecule involved in neuronal development and has been identified as a genetic risk locus for major depressive disorder (MDD). However, its functional role and clinical relevance in MDD remain unclear. This study aimed to evaluate circulating NEGR1 levels and their association with depressive symptom severity, and to explore the in vitro effects of fluoxetine on NEGR1 expression. Methods: In this case–control study, peripheral blood mononuclear cells (PBMCs) were obtained from 40 drug-naïve patients with MDD and 40 healthy controls. NEGR1 mRNA expression was quantified using quantitative real-time PCR. Circulating NEGR1 protein levels were measured in plasma by ELISA. PBMC cultures were treated with fluoxetine in vitro to assess its effect on NEGR1 expression. Depressive symptom severity was evaluated using the Hamilton Depression Rating Scale and Beck Depression Inventory. Results: Circulating NEGR1 protein levels were significantly higher in patients with MDD than in controls (p = 0.01). NEGR1 levels showed a positive correlation with Beck Depression Inventory scores (r = 0.33, p = 0.036). No significant differences were observed in PBMC NEGR1 mRNA expression between groups, and fluoxetine treatment did not significantly affect NEGR1 expression in vitro (p > 0.05). Conclusion: Elevated circulating NEGR1 protein levels are associated with MDD and correlate with symptom severity. These findings suggest that NEGR1 may represent a potential peripheral biomarker candidate for MDD, independent of pharmacological treatment effects. Health sciences/Diseases/Psychiatric disorders/Depression Biological sciences/Neuroscience/Molecular neuroscience Major depressive disorder NEGR1 fluoxetine biomarker peripheral blood mononuclear cells Figures Figure 1 Figure 2 Full Text Additional Declarations The authors declare no competing interests. Supplementary Files Tables.docx Tables Cite Share Download PDF Status: Posted Version 3 posted You are reading this latest preprint version Show more versions 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-4421084","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":539947169,"identity":"3999bfab-a618-4591-a6a2-adf16915e42f","order_by":0,"name":"Burcu 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Disorder\u003c/strong\u003e\u003c/p\u003e","fulltext":[],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":true,"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":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Major depressive disorder, NEGR1, fluoxetine, biomarker, peripheral blood mononuclear cells","lastPublishedDoi":"10.21203/rs.3.rs-4421084/v3","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4421084/v3","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eBackground: Neuronal growth regulator 1 (NEGR1) is a cell adhesion molecule involved in neuronal development and has been identified as a genetic risk locus for major depressive disorder (MDD). However, its functional role and clinical relevance in MDD remain unclear. This study aimed to evaluate circulating NEGR1 levels and their association with depressive symptom severity, and to explore the in vitro effects of fluoxetine on NEGR1 expression.\u003c/p\u003e\n\u003cp\u003eMethods: In this case–control study, peripheral blood mononuclear cells (PBMCs) were obtained from 40 drug-naïve patients with MDD and 40 healthy controls. NEGR1 mRNA expression was quantified using quantitative real-time PCR. Circulating NEGR1 protein levels were measured in plasma by ELISA. PBMC cultures were treated with fluoxetine in vitro to assess its effect on NEGR1 expression. Depressive symptom severity was evaluated using the Hamilton Depression Rating Scale and Beck Depression Inventory.\u003c/p\u003e\n\u003cp\u003eResults: Circulating NEGR1 protein levels were significantly higher in patients with MDD than in controls (p = 0.01). NEGR1 levels showed a positive correlation with Beck Depression Inventory scores (r = 0.33, p = 0.036). No significant differences were observed in PBMC NEGR1 mRNA expression between groups, and fluoxetine treatment did not significantly affect NEGR1 expression in vitro (p \u0026gt; 0.05).\u003c/p\u003e\n\u003cp\u003eConclusion: Elevated circulating NEGR1 protein levels are associated with MDD and correlate with symptom severity. These findings suggest that NEGR1 may represent a potential peripheral biomarker candidate for MDD, independent of pharmacological treatment effects.\u003c/p\u003e\n\u003cp\u003e\u003cbr\u003e\u003c/p\u003e","manuscriptTitle":"Circulating NEGR1 Protein Levels Associate with Symptom Severity in Drug-Naïve Major Depressive Disorder","msid":"","msnumber":"","nonDraftVersions":[{"code":3,"date":"2026-05-12 17:49:44","doi":"10.21203/rs.3.rs-4421084/v3","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}},{"code":2,"date":"2025-11-04 16:17:24","doi":"10.21203/rs.3.rs-4421084/v2","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}},{"code":1,"date":"2024-11-01 08:01:30","doi":"10.21203/rs.3.rs-4421084/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"8a0c1f0f-9815-462e-9d50-f464a7fa6b12","owner":[],"postedDate":"May 12th, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":67512138,"name":"Health sciences/Diseases/Psychiatric disorders/Depression"},{"id":67512139,"name":"Biological sciences/Neuroscience/Molecular neuroscience"}],"tags":[],"updatedAt":"2024-12-02T11:20:30+00:00","versionOfRecord":[],"versionCreatedAt":"2026-05-12 17:49:44","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v3","identity":"rs-4421084","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4421084","identity":"rs-4421084","version":["v3"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}