Structural and functional correlates of serum soluble IL-6 receptor level in patients with bipolar disorder

Inflammation is reported to play a crucial role in the pathogenesis of bipolar disorder (BD). Higher serum levels of soluble interleukin-6 receptor (sIL-6R), which forms a ligand-receptor complex with the potent proinflammatory cytokine IL-6, have been consistently observed in patients with BD. However, the effect of sIL-6R on neural structure and function remains unclear. This study investigated the association between serum sIL-6R levels and the structural and functional connectivity (FC) of the brain in patients with BD.

Seventy-four stable patients with BD-I or BD-II were enrolled from the outpatient clinic. Structural and resting functional MRI and clinical evaluations were performed in all participants, and serum sIL-6R levels were measured. We used an automated surface-based method (FreeSurfer) to measure cortical thickness and a seed-based FC analysis to derive the FC map of the medial prefrontal cortex (mPFC), a key region implicated in the fronto-limbic disconnection hypothesis of BD. Brain-wise regression analyses of cortical thickness and FC mapping on IL-6 levels were performed using a general linear model.

Higher sIL-6R levels were associated with a thinner cortex in the right middle temporal gyrus. Furthermore, higher sIL-6R levels were associated with increased FC between the mPFC and amygdala, pallidum, putamen, and insula and decreased FC between the mPFC and subgenual anterior cingulate cortex and frontal pole.

The results evidence that higher serum inflammatory marker levels are associated with a severer deficit in structural and connectivity abnormalities implicated in BD.