Inflammatory markers and incident depression: Evidence in a population-based prospective study.

The association between pro-inflammatory cytokines and depression is widely acknowledged. However, longitudinal data that show they lead to depression are few. In a community-based sample of older individuals (n = 2761, ages = 55-98 y) in the Singapore Longitudinal Ageing Study (SLAS), we analyzed the associations between inflammatory markers (CRP, IL6, TNFα, and inflammation risk score) and depression (defined as the presence of depressive symptoms, depression history or treatment). Cross-sectional analysis showed that CRP, IL-6 and TNFα were significantly associated with depression at baseline. Longitudinal analysis controlling for a host of potentially confounding risk factors and initial depression revealed that IL-6, TNFα, and inflammation risk score were associated with elevated risk of depression at follow-ups. However, there was no significant association between CRP and subsequent depression after adjusting for sociodemographic, lifestyles and inflammatory medical condition variables. In summary, this prospective study shows that inflammation predicts depression in older adults, and suggests that the heterogeneous findings among studies may be due to differences in study population characteristics, depression, inflammatory markers, and the extent of adjusting for confounders.

Lifetime pathogen burden, inflammatory markers, and depression in community-dwelling older adults.

The link between pathogen exposure and mental health has long been hypothesized, but evidence remains limited. We investigated the association of seropositivity to common pathogens and total pathogen burden with depression and mental health and explored the role of mediating inflammatory cytokines. We profiled in 884 participants in the Singapore Longitudinal Ageing Studies, mean (SD) age: 67.9 (8.1) years, their seropositivities for 11 pathogens (CMV, HSV 1, HSV 2, HHV-6, EBV, VZV, RSV, Dengue, Chikungunya, H. Pylori and Plasmodium) and pathogen burden, Geriatric Depression Scale (GDS) score at baseline and 3-4 and 6-8 years follow-up, and baseline Mental Component Score (MCS) of 12-Item Short Form Survey (SF-12). Inflammatory markers included CRP, TNF-α, IL-6, MIP-1α, sgp130, sTNF-RI, sTNF-RII, C3a, and MCP-2. Controlling for age, sex, ethnicity, education, marital status, living alone, and smoking status, high pathogen burden (7 + cumulative infections) compared to low pathogen burden (1-5 cumulative infections) was significantly associated with period prevalence (the highest GDS score from baseline and follow-up measurements) of depressive symptoms (OR = 2.36, 95% CI = 1.05-5.33) and impaired mental health (OR = 2.25, 95% CI = 1.18-4.30). CMV seropositivity and HSV1 seropositivity, which are highly prevalent and most widely studied, were associated with estimated 2-fold increased odds of depression, but only HSV1 seropositivity was significantly associated with depression after adjusting for confounders. Notably, adjusted for confounders, RSV, H. pylori and Plasmodium seropositivity were significantly associated with increased odds, and Dengue seropositivity was associated with unexpectedly deceased odds of depressive symptoms and impaired mental health. The association of pathogen exposure with depression and mental health were at least in parts explained by inflammatory markers. Adding certain inflammatory markers to the models attenuated or weakened the association. Bootstrap method showed that MIP-1α significantly mediated the association between pathogen burden and mental health. In conclusion, lifelong pathogen burden and specific infections are associated with depression and impaired mental health in older adults.