Dysregulation of cytokine coding genes in peripheral blood of bipolar patients

The role of immune response dysregulation has been previously noticed in the pathogenesis of bipolar disorder (BD).

In the current investigation, we compared expression levels of eight cytokines and a chemokine (CXCL8) in the peripheral blood of BD patients and healthy subjects. All BD patients were in euthymic phase.

We found higher expression of IL-1B, IL-10, IFN-G, TNF-a, TGF-B and IL-2 in male patients compared with male controls (ExR=3.44, P<0.0001, ExR=2.54, P<0.0001; ExR=2.39, P<0.0001; ExR=2.74, P<0.0001; ExR=2.32, P<0.0001; ExR=1.87, P = 0.04 respectively). For these cytokines, no significant differences were found between female patients and female controls. While expression of IL-6 was higher in male patients compared with male controls (ExR=2.07, P = 0.006), in female subjects the opposite trend was detected (ExR=0.44, P = 0.02). However, no significant difference was detected between female subjects. Expression levels of IL-17 were not different between patients and controls or between any subgroups of them. We found significant correlations between expression of IFN-G and age at disease onset (R = 0.25, P = 0.04) as well as expression of CXCL8 and both age of patients and age at disease onset (R = 0.26, P = 0.03; R = 0.25, P = 0.04). Moreover, inverse correlation was detected between expression of TNF-a and age in control group (R=-0.34, P = 0.008).

Combination of transcript levels of six genes could differentiate BD patients from healthy subjects with diagnostic power of 0.85 (Sensitivity=78%, Specificity=80% and P<0.0001). The current investigation highlights the role of cytokine coding genes in the pathogenesis of BD and potentiates them as diagnostic biomarkers.