Associations of Tumor Necrosis Factor-α and Interleukin-1β Levels and Polymorphisms with Post-Stroke Depression

Abstract

Objective: Proinflammatory cytokines have been implicated in the pathophysiology of post-stroke depression (PSD), and their production levels are influenced by the transcriptional activity of genetic polymorphisms. The present study aimed to investigate the roles of tumor necrosis factor (TNF)-α and interleukin (IL)-1β in the serum on the risk of PSD while taking into account the TNF-α -850C/T and -308G/A polymorphisms and the IL-1β -511C/T and +3953C/T polymorphisms.

Methods: A total of 286 patients were evaluated at 2 weeks post stroke and 222 (78%) of these patients were followed up 1 year later. Depressive (major or minor) disorders were diagnosed according to Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria during both examinations; evaluations of cytokine concentrations and polymorphisms and demographic and clinical covariates were performed at 2 weeks. The effects of TNF-α and IL-1β concentrations and genotypes on PSD status were investigated using multivariate logistic regression models.

Results: Higher TNF-α levels were associated with PSD at 2 weeks in the presence of the -850T allele with a significant interaction term; higher IL-1β levels were associated with PSD at 2 weeks in the presence of the -511T allele with a borderline significant interaction term and with any +3953C/T polymorphism without a significant interaction term. No associations were found with PSD at 1 year.

Conclusions: These findings indicate the important roles that TNF-α and IL-1β serum levels play regarding the risk of PSD, particularly during the acute phase of stroke and in patients with genetic susceptibility.

Keywords: Depression; cytokines; genetics; interaction; stroke.