Major depression and enhanced molecular senescence abnormalities in young and middle-aged adults

Breno S Diniz,Brenda W J H Penninx,Etienne Sibille,Charles F Reynolds Iii,Mariska Bot

doi:10.1038/s41398-019-0541-3

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

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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