Abstract

Recent evidence suggests a significant overlap in biological changes between major depression and aging across the lifespan. We aim to evaluate the impact of a major depressive episode on the Senescence-Associated Secretory Phenotype (SASP) index, a dynamic secretory molecular pattern indicative of cellular senescence. We also tested the potential moderators of the association between major depression and the SASP index. We included 1165 young and middle-aged adults (527 with a current major depressive episode (cMDE) and 638 with no lifetime history of depression) from a community-based cohort from the Netherlands. We calculated the SASP index based on a previously developed composite index involving 19 biomarkers. cMDE had higher SASP index values (t(1163) = 2.93, p = 0.003) compared to controls in the univariate analysis. After controlling for sociodemographic and somatic health covariates, there was no significant association between cMDE and SASP index (F(1,1158) = 1.09, p = 0.29). Those with the most severe depressive episodes had significantly higher SASP indices compared to those with mild-to-moderate cMDE and controls (F(2,1162) = 6.73, p = 0.001). We found a significant interaction between cMDE and overweight (F(1,1164) = 5.1, p = 0.028): those with comorbid cMDE and overweight had the highest SASP index. Our study demonstrated a complex interaction between cMDE and medical morbidity, especially overweight, on the SASP index, suggesting that their coexistence aggravate age-related biological processes. Moreover, higher SASP index can be a biomarker for more severe depressive episodes.

Highlights

  • Major depressive disorders (MDD) across the lifespan are among the most common mental disorders in the general population, with a lifetime prevalence ranging from 5 to 15%1,2

  • We explored the association between the Senescence-Associated Secretory Phenotype (SASP) index and characteristics related to the depressive episode, and whether demographic and somatic health variables contributed to the association between MDD and cellular senescence

  • Antidepressant use did not significantly influence the SASP index among individuals with MDD (t = 0.016, df = 525, p = 0.98); all individuals in the current major depressive episode (cMDE) group were included in the analysis

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Summary

Introduction

Major depressive disorders (MDD) across the lifespan are among the most common mental disorders in the general population, with a lifetime prevalence ranging from 5 to 15%1,2. Aside from its high prevalence, MDD is the second most disabling health condition worldwide (after cardiovascular disease), has a chronic and relapsing course, poor treatment response and is linked to higher risk of developing chronic and disabling conditions[3]. The molecular mechanisms linking MDD to poorer health outcomes are not well understood, but probably involve the interaction of depression with medical morbidity, and ageor senescence-related biological processes[10,11]. Understanding how MDD and somatic health variables affect biological mechanisms associated with senescence can help explain why these conditions increase the risk of age-related disorders and disability, as well as identifying novel targets for intervention

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