Effects of interleukin-6, interleukin-18, and statin use, evaluated at acute stroke, on post-stroke depression during 1-year follow-up

Abstract

Proinflammatory cytokines are associated with the development of post-stroke depression (PSD). Statins are thought to possess anti-inflammatory properties but their interactions with cytokines regarding the risk of PSD have yet to be investigated. Thus, the present study aimed to determine whether interleukin (IL)-6 and IL-18 were associated with the development of depression at 2 weeks and 1year after stroke using a longitudinal post-stroke cohort. Furthermore, this study examined the potential interactions between statin use and cytokines on PSD. For this study, 286 patients were evaluated 2 weeks after stroke and 222 patients were followed-up 1year later. Depression was diagnosed using criteria from the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM-IV) and then categorized into no PSD or any PSD, which included diagnoses of both major and minor depression. The effects of IL-6 and IL-18 on PSD as well as their interaction with a statin at both examination time-points were investigated using a multivariate logistic regression model. Higher IL-6 and IL-18 levels were independently associated with depressive disorders within 2 weeks and at 1year after stroke. When stratified by statin use, these significant associations were more evident in patients who did not use a statin. Furthermore, there was a significant interaction between statin use and IL-6 on the presence of a depressive disorder at 1year. The present findings support the cytokine hypothesis of PSD and indicate that the preventive effects of statin use against PSD may be mediated by its interactions with IL-6.