Inflammatory cytokines and cognitive functioning in early-stage bipolar I disorder

Background: Increased circulating inflammatory cytokines is a replicated finding in bipolar I disorder (BDI). Pro-inflammatory cytokines such as TNF alpha, IL-6 and IL-1 have also been associated with poorer cognitive functioning in patients with longer illness duration. However, the effect of inflammatory cytokines on cognition in early stage patients is not yet known. Here, we investigate the relationship between cytokines and cognition in BDI patients within three years of diagnosis. Methods: Serum pro-inflammatory (TNF alpha, IL-6 and IL-1 alpha) and anti-inflammatory (IL-4 and IL-10) cytokine levels were compared between 51 early stage BDI patients and 20 healthy controls. 46 patients completed neuropsychological testing, and multiple regression analysis was used to assess the association between cytokine levels and cognition after accounting for relevant clinical and demographic variables. Results: TNF alpha was elevated at trend level significance in BDI patients compared to healthy controls, and was negatively associated with global cognition, processing speed, and working memory in patients. IL-6, IL-1 alpha, IL-4 and IL-10 levels were comparable between groups and were not significantly associated with cognition. Limitations: Direct causation cannot be established in this cross-sectional study; in addition, cytokine levels were not taken on the same day as neuropsychological testing for all patients. Conclusions: TNF alpha may negatively impact cognition in early BDI. While replication is required in larger samples, these results suggest that inhibition of TNF alpha activity might be a strategy to preserve cognition in newly diagnosed BDI patients.