Abstract
BackgroundIt is well established that there is a link between inflammation and depression, with several studies reporting increased circulating levels of the pro-inflammatory cytokine, interleukin-6 (IL6), in depressed individuals. Peripheral epigenetic marks, including DNA methylation, hold promise as biomarkers for a range of complex conditions, with potential to inform diagnosis and tailor interventions. The aim of this study was to determine whether individuals with depression display differential methylation of the IL6 gene promoter compared to individuals without depression.MethodsThe ESPRIT study of later life neuropsychiatric disorders used a random sampling framework to select non-institutionalised participants aged ≥65 years and over living in the Montpellier region of France. Major depressive disorder (MDD) was assessed using the Mini International Neuropsychiatric Interview (MINI) according to DSM-IV criteria. High levels of depressive symptoms were defined as a score of ≥16 on the Centre for Epidemiologic Studies Depression Scale (CES-D). IL6 promoter DNA methylation was measured on a sub-sample of 380 participants who provided buccal samples.ResultsIndividuals with depression (current MDD or high depressive symptoms) had lower IL6 methylation levels at one of the four sites investigated, however the effect size was small (∆ 2.4%, SE 0.009, p = 0.006). Interestingly, antidepressant use was independently associated with higher IL-6 methylation at the same site (∆ 4.6%, SE 0.019, p = 0.015). In multivariate linear regression analyses adjusting for covariates, including sex and smoking status, these associations remained. There was no effect modification when considering IL6 genotype.ConclusionThis study presents evidence that IL6 methylation may be a marker of depression status in older individuals, however further work is now needed to replicate these findings and to assess the association with inflammatory status of individuals.
Highlights
It is well established that there is a link between inflammation and depression, with several studies reporting increased circulating levels of the pro-inflammatory cytokine, interleukin-6 (IL6), in depressed individuals
Given that increased IL6 protein levels have been reported in Major depressive disorder (MDD) and that promoter gene methylation is commonly associated with reduced gene transcription, we hypothesised that depression would be associated with decreased IL6 DNA methylation
Depressed participants were significantly more likely to be female, have a lower education level, live alone, and have a higher frequency of cognitive impairment. They were significantly more likely to use antidepressants (p < 0.0001). These characteristics were considered as potential cofounders which could influence the association between depression and IL6 methylation
Summary
It is well established that there is a link between inflammation and depression, with several studies reporting increased circulating levels of the pro-inflammatory cytokine, interleukin-6 (IL6), in depressed individuals. Depression in the elderly is common and often a chronic medical illness with high disease burden [1]. It is associated with heightened comorbidity [2] and an increased risk of mortality [3]. Cytokine treatments have been linked to the occurrence of new depressive episodes [6] and individuals with major depression have a high frequency of comorbid chronic inflammatory diseases [7].
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