Interleukin-1 Receptor Antagonist and Incident Depressive Symptoms Over 6 Years in Older Persons: The InCHIANTI Study
Received 24 June 2008; received in revised form 6 November 2008; accepted 8 November 2008. published online 29 December 2008.
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.
cDepartment of Psychiatry and EMGO Institute, VU University Medical Center, Amsterdam, The Netherlands
dLaboratory of Epidemiology Demography and Biometry, National Institute on Aging, Bethesda
eLongitudinal Studies Section, Clinical Research Branch, National Institute on Aging, Baltimore, Maryland
Address reprint requests to Luigi Ferrucci, M.D., Ph.D., Chief, Longitudinal Studies Section, National Institute on Aging, Clinical Research Branch, Harbor Hospital Center-Room NM540, 3001 S. Hanover Street, Baltimore, MD 21225
ABSTRACT