Subjective mental health, incidence of depressive symptoms in later life, and the role of epigenetics: results from two longitudinal cohort studies

Laura Perna,Pamela R Matias-Garcia,Yan Zhang,Tobias Wiechmann,Andreas Ihle,Ben Schöttker,Ute Mons,Melanie Waldenberger,Annette Peters,Beate Wild,Hermann Brenner,Matthias Kliegel,Lars Schwettmann,Karl-Heinz Ladwig

doi:10.1038/s41398-020-00997-x

Abstract

The role of self-perceived general health in predicting morbidity and mortality among older people is established. The predictive value of self-perceived mental health and of its possible biological underpinnings for future depressive symptoms is unexplored. This study aimed to assess the role of mental health-related quality of life (HRQOL) and of its epigenetic markers in predicting depressive symptoms among older people without lifetime history of depression. Data were based on a subgroup (n = 1 492) of participants of the longitudinal ESTHER study. An epigenome-wide association study (EWAS) of mental HRQOL was conducted using DNA from baseline whole blood samples and logistic regression analyses were performed to assess the predictive value of methylation beta values of EWAS identified CpGs for incidence of depressive symptoms in later life. The methylation analyses were replicated in the independent KORA cohort (n = 890) and a meta-analysis of the two studies was conducted. Results of the meta-analysis showed that participants with beta values of cg27115863 within quartile 1 (Q1) had nearly a two-fold increased risk of developing depressive symptoms compared to participants with beta values within Q4 (ORQ1vsQ4 = 1.80; CI 1.25–2.61). In the ESTHER study the predictive value of subjective mental health for future depressive symptoms was also assessed and for 10-unit increase in mental HRQOL scores the odds for incident depressive symptoms were reduced by 54% (OR 0.46; CI 0.40–0.54). These findings suggest that subjective mental health and hypomethylation at cg27115863 are predictive of depressive symptoms, possibly through the activation of inflammatory signaling pathway.

Highlights

Depression is a common mental disorder and a leading cause of disability worldwide[1]
This study aimed to assess whether mental health-related quality of life (HRQOL) is predictive of depressive symptoms and to perform an epigenome-wide association study (EWAS) of mental HRQOL to explore whether the resulting epigenetic markers would predict depressive symptoms among older people without lifetime history of a physician diagnosis of depression and free of depression at baseline over an observational period of 5 years
After exclusion of participants with invalidated Geriatric Depression Scale (GDS) (n = 95) and lifetime history of a physician diagnosis of depression (n = 246, thereof 19 with invalidated GDS), 1492 ESTHER participants remained for regression analyses

Summary

Introduction

Depression is a common mental disorder and a leading cause of disability worldwide[1]. Prevalence of depression decreases in older age, but especially among people older than 65 years (late-onset depression) depression is more closely associated with suicide and decreased physical, cognitive, and social functioning than early-onset depression[2]. Subthreshold depressive disorders, whose impact on health status is comparable to full-blown depressive episodes[3], have a high prevalence among older adults[2,4]. The exact molecular mechanisms underlying depression are still unclear, but a growing body of evidence suggests that DNA methylation is a candidate mechanism contributing to explaining the molecular basis of late-onset depression[5]. There is a lack of longitudinal studies investigating the predictive value of DNA methylation in depression with most studies being cross-sectional and having a small sample size. Epigenetic markers of depression have been mainly investigated among people

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Results