Interleukin-1 Receptor Antagonist and Incident Depressive Symptoms Over 6 Years in Older Persons: The InCHIANTI Study

Background: We test the hypothesis that in older persons higher plasma levels of inflammatory markers predict the development of depressive symptoms during a 6-year follow-up. Method: This study is part of the InCHIANTI (Invecchiare in Chianti, aging in the Chianti area) study, a prospective population-based study of older persons. The sample consisted of 991 participants, ages 65 years and older. Serum levels of C-reactive protein, interleukin (IL)-1β, IL-1 receptor antagonist (ra), tumor necrosis factor-α, IL-6, IL-6 receptor, and IL-18 were measured. Depressive symptoms were assessed at baseline and at the 3- and 6-year follow-ups with the Center for Epidemiological Studies-Depression Scale (CES-D). Depressed mood was defined as CES-D > 20. Potential confounders were baseline variables related to sociodemographic, somatic health, and functional status. Results: At baseline, IL-1ra levels were significantly higher (p = .004) in depressed compared with nondepressed participants. After adjustment for confounders, among subjects free of depression at baseline, those in the third and fourth IL-1ra quartiles compared with those in the lowest quartile had, respectively, a 2.32-fold (95% confidence interval: 1.21-4.42, p = .01) and 2.78-fold (95% confidence interval: 1.47-5.26, p = .002) higher risk of developing depressed mood during a 6-year follow-up. Conclusions: In old age, persons with high plasma levels of IL1-ra had a higher risk of developing depressive symptoms over time. These findings suggest a potential causal role for inflammation in the development of depressive symptoms in older persons.