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Study finds biomarkers for older adults with depression

To summarize: Biological changes due to aging may be one mechanism why older adults with depression do not have full resolution of symptoms after taking antidepressants.

resource: University of Connecticut

Major depression in older adults is very common, can lead to disability, and increase the risk of many diseases of aging, including Alzheimer’s disease and other dementias, cardiovascular problems and even death. As such, it poses a significant public health concern, especially given the growing number of older adults in the United States and around the world.

Many older adults with depression do not experience complete relief from their depressive symptoms after receiving antidepressants.

Amelioration or complete resolution of depression in older adults is a significant clinical challenge, with approximately 50% of patients experiencing persistent depressive symptoms after antidepressant treatment.

The persistence of depressive symptoms is at the root of depleted mental health, increased disability, accelerated cognitive decline, and premature aging in older adults.

Therefore, identifying the mechanisms and factors associated with treatment outcomes in this population is key to improving treatment and identifying individuals for whom antidepressant therapy is more effective.

Breno Diniz, PhD, Associate Professor of Psychiatry at UConn Health’s UConn Center on Aging, and colleagues published June 30, 2022 in JAMA Network Open.

They used a recently developed composite biomarker index associated with cellular and molecular aging [the senescence-associated secretory phenotype, SASP] To test the hypothesis that biological changes that occur with age are one of the mechanisms of poor treatment outcomes for depression in older adults.

They found that higher SASP index scores were significantly associated with a lower likelihood of complete remission of depressive symptoms after antidepressant treatment.

Many older adults with depression do not experience complete relief from their depressive symptoms after receiving antidepressants.Image is in the public domain

These findings are important because they underscore the importance of age-related biological abnormalities, reflected in the SASP index, as a potential mechanism associated with antidepressant treatment resistance in older adults.

This investigation opens up new possibilities for investigating alternative interventions to improve the odds of responding to antidepressant treatment in this population, for example, by testing whether antiaging drugs can improve treatment remission rates in older adults with depression.

In addition, the measurement of SASP index biomarkers can help identify those individuals who are refractory to treatment at the start of treatment.

These findings could point the way forward for aging-targeted interventions guided by geriatrics to improve depressive symptoms in older adults.

About This Aging and Depression Research News

author: News office
resource: University of Connecticut
touch: Press Office – University of Connecticut
picture: Image is in the public domain

Original research: Open access.
“Association of Molecular Aging Markers with Clinical Features and Treatment Outcomes in Later-Life Depression” by Breno S. Diniz et al. JAMA Network Open


Association of molecular aging markers with clinical features and treatment outcomes in later-life depression


Many older adults with depression are not in remission with antidepressants, and markers of cellular aging in later-life depression (LLD) are associated with more severe depression, more executive dysfunction and higher medical disease burden. As these clinical features are associated with remission of LLD, abnormalities in molecular and cellular senescence may be the underlying biological mechanisms underlying the poor response to therapy in this population.


To investigate whether the aging-associated secretory phenotype (SASP) index is associated with the likelihood of remission of depressive episodes in older adults.

Design, Setup and Participants

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A non-randomized, open-label clinical trial was conducted between August 2009 and August 2014 in Pittsburgh, Pennsylvania; St. Louis, Missouri; and Toronto, Ontario, Canada, among older adults currently experiencing a major depressive episode. Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition, revised text) Diagnostic Criteria. Biomarker profiling data is reported on archived plasma samples from a clinical trial running in March 2021. The data analysis period was from June 2021 to November 2021.


Venlafaxine extended-release (dose range of 37.5 mg to 300 mg per day) for up to 12 weeks.

Main results and measures

The association between a composite biomarker-based index (SASP index) and treatment remission in older adults with major depressive disorder was measured using clinical data and blood samples.


There were 416 participants with a mean (SD) age of 60.02 (7.13) years; 64% (265 participants) were self-reported females with a mean (SD) Montgomery-Asberg Depression Rating Scale score of 26.6 (5.7). Higher SASP index scores were independently associated with higher non-response rates, with a 1-unit increase in SASP index score increasing the odds of non-response by 19% (adjusted odds ratio, 1.19; 95% CI, 1.05-1.35; phosphorus= .006). In contrast, no single SASP factor was associated with LLD remission.

Conclusions and Relevance

Using clinical data and blood samples from non-randomized clinical trials, the results of this study demonstrate that molecular and cellular senescence, as measured by the SASP index, is associated with poorer treatment outcomes in LLD. Combining index scores reflecting interconnected biological processes with other molecular, clinical, and neuroimaging markers may help assess outcomes of antidepressant therapy. These findings provide a path forward for aging-targeted interventions guided by geriatric science to improve remission rates in LLD.

Trial registration Identifier: NCT00892047

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