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Senescence Markers Linked with Worse Treatment Outcomes in Late-Life Depression

Jolynn Tumolo

Higher scores on the senescence-associated secretory phenotype (SASP) index are significantly linked with worse treatment outcomes in older adults with a major depressive episode, according to findings published online in JAMA Network Open.

“Our study also demonstrates that a composite index, integrating biomarkers reflecting distinct but interrelated biological processes, is superior to any single biomarkers in the association with treatment remission in late-life depression,” wrote study lead author Breno S. Diniz, MD, PhD, of the University of Connecticut School of Medicine, Farmington, and coauthors.

The trial included 416 adults, age 60 and older, who were diagnosed with major depressive disorder and experiencing a current major depressive episode. Participants were treated for up to 12 weeks with open-label extended-release venlafaxine, with doses ranging from 37.5 mg to 300 mg daily. Blood samples and clinical data were used to gauge associations between SASP index scores and treatment remission.

Related: Distinct Gene Expression Signature Identified in Group of Patients With MDD

Higher scores on the SASP index, a composite measure of 22 molecular and cellular senescence biomarkers, were associated with lower likelihood of remission of the major depressive episode to venlafaxine treatment, according to the study. An increase of 1 unit on the SASP index score was linked with a 19% higher risk of nonremission.

When researchers investigated associations between each of the 22 SASP biomarkers and treatment outcomes, however, they found no links between individual SASP factors and nonremission.

“Combining this index score reflecting interrelated biological processes with other molecular, clinical, and neuroimaging markers may be useful in evaluating antidepressant treatment outcomes,” researchers wrote. “These findings inform a path forward for geroscience-guided interventions targeting senescence to improve remission rates in late-life depression.”

Reference

Diniz BS, Mulsant BH, Reynolds CF 3rd, et al. Association of molecular senescence markers in late-life depression with clinical characteristics and treatment outcome. JAMA Netw Open. Published online June 1, 2022. doi: 10.1001/jamanetworkopen.2022.19678

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