Association between the serotonin transporter and cytokines: Implications for the pathophysiology of bipolar disorder

Background: Reduced brain serotonin transporter (SERT) has been demonstrated in bipolar disorder (BD). The aim of this study was to explore the potential role of cytokines on reduced SERT in BD. Methods: Twenty-eight BD type I patients and 28 age- and gender-matched healthy controls (HCs) were recruited. Single photon emission computed tomography with the radiotracer 1231 ADAM was used for SERT imaging. Regions of interest included the midbrain, thalamus, putamen and caudate. Seven cytokines, including tumor necrosis factor-alpha (TNIF-alpha), interferon-gamma (IFN-gamma), interleukin-1 alpha (IL-1 alpha), IL-1 beta, IL-4, IL-6 and IL-10, were measured using an enzyme linked immune-sorbent assay. Results: SERT availability in the midbrain and caudate was significantly lower in BD compared to HCs. IL-1 beta was significantly lower, whereas IL-10 was significantly higher in BD compared to HCs. Multiple linear regression analyses revealed that there were associations between cytokines, IL-1 alpha, IL-1 beta, IL-6 and SERT availability in the midbrain but not in the thalamus, putamen and caudate. Furthermore, linear mixed effect analyses demonstrated that these associations were not different between HCs and BD. Conclusion: While many cytokines have been proposed to be important in the pathophysiology of BD, our results demonstrated that significant associations between cytokines and SERT availability may explain the role of cytokines in mood regulation. However, these associations were not different between HCs and BD, which imply the role of these cytokines is not specific for BD. (C) 2015 Elsevier B.V. All rights reserved.