Soluble interleukin-6 receptor-associated functional connectivity as an indicator of bipolar disorder prognosis

Predictive neurobiological markers are essential for indicating the prognosis of patients with bipolar disorder (BD). Exploring the association between soluble interleukin-6 receptor (sIL-6R) and alterations in functional connectivity (FC) may contribute to an improved understanding of the pathophysiology of BD. Therefore, on the basis of the heterogeneous types of inflammation exhibited by patients with BD, sIL-6-associated FC was investigated as a predictor of various treatment responses.

A total of 165 patients with BD were recruited and assessed using the Young Mania Rating Scale, Montgomery-Åsberg Depression Rating Scale (MADRS), Personal and Social Performance (PSP) Scale, and Global Assessment of Functioning (GAF) Scale at baseline and 1-year follow-up. Agglomerative hierarchical clustering by using sIL-6R-associated FC was used to divide patients with BD into subgroups. Then, the changes in symptom and functioning scores among the clusters were compared.

Regarding major FC, the subgroup that had a significantly decreased MADRS score and increased PSP and GAF scores exhibited lower connectivity between the medial frontal network (MFN) and motor network (MON) and within the MON and higher connectivity between the MFN and default mode network (DMN) and within the MFN than the other subgroup. Moreover, these altered FC findings may be remediated through a mildly increased sIL-6R level.

These altered connections displayed a counteractive direction on the most pronounced abnormal FC of patients with BD and are recommended to help patients offset the detrimental effects of neuroinflammation.