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

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 1 year 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 1 year 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 1 year 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 1 year. 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.