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dc.contributor.authorDiniz, B.S.
dc.contributor.authorMulsant, B.H.
dc.contributor.authorReynolds, C.F., III
dc.contributor.authorBlumberger, D.M.
dc.contributor.authorKarp, J.F.
dc.contributor.authorButters, M.A.
dc.contributor.authorMendes-Silva, A.P.
dc.contributor.authorVieira, E.L.
dc.contributor.authorTseng, G.
dc.contributor.authorLenze, E.J.
dc.date.accessioned2022-08-25T00:52:11Z
dc.date.available2022-08-25T00:52:11Z
dc.date.issued2022
dc.identifier.citationDiniz, B. S., Mulsant, B. H., Reynolds, C. F., Iii, Blumberger, D. M., Karp, J. F., Butters, M. A., Mendes-Silva, A. P., Vieira, E. L., Tseng, G., & Lenze, E. J. (2022). Association of Molecular Senescence Markers in Late-Life Depression with Clinical Characteristics and Treatment Outcome. JAMA Network Open, 5(6), E2219678.
dc.identifier.issn2574-3805
dc.identifier.pmid35771573
dc.identifier.doi10.1001/jamanetworkopen.2022.19678
dc.identifier.urihttp://hdl.handle.net/10150/665947
dc.description.abstractImportance: Many older adults with depression do not experience remission with antidepressant treatment, and markers of cellular senescence in late-life depression (LLD) are associated with greater severity of depression, greater executive dysfunction, and higher medical illness burden. Since these clinical characteristics are associated with remission in LLD, molecular and cellular senescence abnormalities could be a possible biological mechanism underlying poor treatment response in this population. Objective: To examine whether the senescence-associated secretory phenotype (SASP) index was associated with the likelihood of remission from a depressive episode in older adults. Design, Setting, and Participants: A nonrandomized, open-label clinical trial was conducted between August 2009 and August 2014 in Pittsburgh, Pennsylvania; St Louis, Missouri; and Toronto, Ontario, Canada, with older adults in a current major depressive episode according to the Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition, Text Revision) diagnostic criteria. Data from biomarker analyses were reported according to the clinical trial archived plasma samples run in March 2021. Data were analyzed from June to November 2021. Exposure: Venlafaxine extended release (dose ranging from 37.5 mg to 300 mg daily) for up to 12 weeks. Main Outcomes and Measures: The association between a composite biomarker-based index (SASP index) and treatment remission in older adults with major depression was measured using clinical data and blood samples. Results: There were 416 participants with a mean (SD) age of 60.02 (7.13) years; 64% (265 participants) were self-reported female, and the mean (SD) Montgomery-Asberg Depression Rating Scale score was 26.6 (5.7). Higher SASP index scores were independently associated with higher rates of nonremission, with an increase of 1 unit in the SASP index score increasing the odds of nonremission by 19% (adjusted odds ratio, 1.19; 95% CI, 1.05-1.35; P =.006). In contrast, no individual SASP factors were associated with remission in LLD. Conclusions and Relevance: Using clinical data and blood samples from a nonrandomized clinical trial, the results of this study suggest that molecular and cellular senescence, as measured with the SASP index, is associated with worse treatment outcomes in LLD. Combining this index score reflecting interrelated biological processes with other molecular, clinical, and neuroimaging markers may be useful in evaluating antidepressant treatment outcomes. These findings inform a path forward for geroscience-guided interventions targeting senescence to improve remission rates in LLD. Trial Registration: ClinicalTrials.gov Identifier: NCT00892047. © 2022 American Medical Association. All rights reserved.
dc.language.isoen
dc.publisherAmerican Medical Association
dc.rightsCopyright © 2022 Diniz BS et al. This is an open access article distributed under the terms of the CC-BY License.
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.titleAssociation of Molecular Senescence Markers in Late-Life Depression with Clinical Characteristics and Treatment Outcome
dc.typeArticle
dc.typetext
dc.contributor.departmentDepartment of Psychiatry, University of Arizona, College of Medicine
dc.identifier.journalJAMA Network Open
dc.description.noteOpen access journal
dc.description.collectioninformationThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at repository@u.library.arizona.edu.
dc.eprint.versionFinal published version
dc.source.journaltitleJAMA Network Open
refterms.dateFOA2022-08-25T00:52:11Z


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Copyright © 2022 Diniz BS et al. This is an open access article distributed under the terms of the CC-BY License.
Except where otherwise noted, this item's license is described as Copyright © 2022 Diniz BS et al. This is an open access article distributed under the terms of the CC-BY License.