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

doi:10.1016/j.biopsych.2008.11.011

Biological Psychiatry

Volume 65, Issue 11, 1 June 2009, Pages 973-978

https://doi.org/10.1016/j.biopsych.2008.11.011 Get rights and content

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.

Section snippets

Study Population

Participants were part of the InCHIANTI (Invecchiare in Chianti, aging in the Chianti area) study, a prospective population-based study of older persons in Tuscany, Italy, designed to investigate factors contributing to decline in mobility function in later life. A description of the study rationale, design, and method is given elsewhere (23). Briefly, in 1998–1999 the sample was randomly selected from two sites, Greve in Chianti and Bagno a Ripoli, with a multistage stratified sampling method.

Results

The mean age of the study sample was 75 ± 7 years, and 55.9% were women; 21.5% had depressed mood at baseline. As shown in Table 1, depressed persons were older; more often women; less likely to be smokers or heavy alcohol drinkers; took more drugs, antidepressant and NSAID; had a lower MMSE score; and were more likely to have hypertension, congestive heart failure, and hip arthritis. Furthermore persons with depressed mood were more likely to be disabled and sedentary and had lower SPPB

Discussion

With data from a population-based study in older persons, we examined the relationship between plasma inflammatory markers and symptoms of depression. We found evidence of a cross-sectional and prospective independent association between IL-1ra and depressive symptoms assessed by CES-D. Several cross-sectional studies (1, 2, 10) found a significant association between depression and high serum IL-1ra. In an experimental study in healthy young men (13) positive correlations were found between

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

Background

Method

Results

Conclusions

Section snippets

Study Population

Results

Discussion

J Affect Disord

Cytokine

Prog Neuropsychopharmacol Biol Psychiatry

Prog Neuropsychopharmacol Biol Psychiatry

Psychiatry Res

Cytokine

Psychiatry Res

J Affect Disord

Neuropsychopharmacology

Brain Behav Immun

Biol Psychiatry

Biol Psychiatry

Blood

J Affect Disord

Exp Gerontol

J Am Coll Cardiol

Lancet

J Neuroimmunol

Brain Behav Immun

Psychiatry Res

Psychiatry Res

Neuropsychopharmacology

Lancet

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