Interleukin-1 receptor antagonist and incident depressive symptoms over 6 years in older persons: the InCHIANTI study

Biol Psychiatry. 2009 Jun 1;65(11):973-8. doi: 10.1016/j.biopsych.2008.11.011. Epub 2008 Dec 25.


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)-1beta, IL-1 receptor antagonist (ra), tumor necrosis factor-alpha, 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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Aged
  • Aged, 80 and over
  • C-Reactive Protein / metabolism
  • Chi-Square Distribution
  • Community Health Planning
  • Depression / blood*
  • Depression / epidemiology*
  • Female
  • Humans
  • Incidence
  • Interleukin 1 Receptor Antagonist Protein / blood*
  • Interleukin-1beta / blood
  • Interleukin-6 / blood
  • Interleukin-8 / blood
  • Italy
  • Longitudinal Studies
  • Male
  • Psychiatric Status Rating Scales
  • Receptors, Interleukin-6 / blood
  • Tumor Necrosis Factor-alpha / blood


  • Interleukin 1 Receptor Antagonist Protein
  • Interleukin-1beta
  • Interleukin-6
  • Interleukin-8
  • Receptors, Interleukin-6
  • Tumor Necrosis Factor-alpha
  • C-Reactive Protein