Interactions between pro-inflammatory cytokines and statins on depression in patients with acute coronary syndrome

Objective: Pro-inflammatory cytokines are associated with the development of depression and statins exert anti-inflammatory and antidepressant effects. The present study aimed to investigate associations between interleukin (IL)-6 and IL-18 and depression in patients with acute coronary syndrome (ACS) and potential interactions between statin use and pro-inflammatory cytokines on depression in this population. Methods: We used pooled datasets from 1-year follow-up data from a 24-week randomized double-blind placebo-controlled trial (RCT) of escitalopram for treatment of depressive disorder and data from a naturalistic, prospective, observational cohort study in patients with ACS. IL-6 and IL-18 levels were measured at baseline. Logistic regression models were used to investigate independent associations of IL-6/IL-18 levels with depressive disorder at baseline and at 1 year. We repeated all analyses by reference to statin use to determine whether any significant association emerged. Results: Of the 969 participants, 378 (39.0%) had major or minor depression at baseline. Of 711 patients followed-up at 1 year, 183 (25.7%) had depression. Logistic regression analysis showed that higher IL-6 and IL-18 levels at baseline were significantly associated with baseline depression after adjusting for other variables (adjusted p-values = 0.005 and 0.001, respectively). IL-6 and IL-18 levels were also significantly higher in patients with depression at the 1-year follow-up after adjusting for other variables amongst those not taking statins (adjusted p-values = 0.040 and 0.004, respectively); but this was not the case in patients taking statins. Conclusion: Levels of pro-inflammatory cytokines appear to predict development of depression after ACS and statins attenuate the effects of cytokines on depression.