Relationship of cytokines with brain serotonin transporter in bipolar I disorder

Objective: The aim of this study was to investigate the interaction of cytokines and brain serotonin transporter (SERT) in bipolar disorder (BD).

Methods: Twenty-eight BD type I patients and 28 age- and sex-matched healthy controls (HCs) were recruited. Single photon emission computed tomography with the radiotracer 123I-ADAM was used for the SERT image. Regions of interest included the midbrain, thalamus, putamen and caudate. Seven cytokines included tumor necrosis factor-α (TNF-α), interferon-γ (IFNγ), interleukin-1α (IL-1α), IL-1β, IL-4, IL-6 and IL-10 were measured using an enzyme-linked immune-sorbent assay. Four ratios included IFN-γ/IL-4, IFN-γ/IL-10, IL-1β/IL-6, and IL-1β/IL-10 was compared and correlated with the SERT availability between BD and HCs.

Results: The SERT availability in the midbrain and caudate was significantly lower in BD than in HCs. IL-1β was significantly lower, whereas IL-10 was significantly higher in BD than those in HCs. The ratio of IL-1β/IL-10 was significantly lower in BD compared with HCs. Pearson’s correlation showed that IL-1α was significantly correlated with the SERT availability in the midbrain and caudate, TNF-α was significantly correlated with the SERT availability in the thalamus in HCs. However, these correlations cannot be found in BD. A stepwise regression analysis considering all cytokines supported the correlation results. Only the ratio of IL-1β/IL-6 was well correlated with the SERT availability in the caudate.

Conclusion: This study for the first time demonstrates the association of different cytokines on the SERT availability in different brain regions. Apparently, IL-1α plays an important role in regulating the SERT availability in HCs, but this relationship was disrupted in BD.