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 (OR_Q1vsQ4= 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.

自我感知的总体健康状况在预测老年人发病率和死亡率方面的作用已经确立。自我感知的心理健康及其对未来抑郁症状可能的生物学基础的预测价值尚未得到探索。本研究旨在评估心理健康相关生活质量 (HRQOL) 及其表观遗传标记在预测没有终生抑郁症史的老年人的抑郁症状中的作用。数据基于一个亚组 ( n = 1 492) 纵向 ESTHER 研究的参与者。使用来自基线全血样本的 DNA 进行了精神 HRQOL 的全表观基因组关联研究 (EWAS)，并进行逻辑回归分析以评估 EWAS 鉴定的 CpG 的甲基化β值对晚年抑郁症状发生率的预测价值。在独立的 KORA 队列 ( n  = 890)中重复了甲基化分析，并对两项研究进行了荟萃分析。荟萃分析的结果表明，随着四分位1（Q内cg27115863的测试值参与者₁）有近两倍相比，参与者中Q对称性参数发展的抑郁症状的风险增加₄（OR _Q1vsQ4= 1.80; CI 1.25–2.61）。在 ESTHER 研究中，还评估了主观心理健康对未来抑郁症状的预测价值，心理 HRQOL 分数每增加 10 个单位，出现抑郁症状的几率就会降低 54%（OR 0.46；CI 0.40-0.54）。这些发现表明 cg27115863 的主观心理健康和低甲基化可预测抑郁症状，可能是通过炎症信号通路的激活。