Inflammation is Correlated with Abnormal Functional Connectivity in Unmedicated Bipolar Depression: A Resting State FMRI Study

Abstract

Objectives Inflammation might play a role in bipolar disorder (BD), but it remains unclear the relationship between inflammation and brain structural and functional abnormalities in patients with BD. In this study, we focused on the alterations of functional connectivity (FC), peripheral pro-inflammatory cytokines and their correlations to investigate the role of inflammation in FC in BD depression.Methods In this study, 42 unmedicated patients with BD II depression and 62 healthy controls (HCs) were enrolled. Resting-state-functional magnetic resonance imaging (rs-fMRI) was performed in all participants and independent component analysis (ICA) was used. Serum levels of Interleukin-6 (IL-6) and Interleukin-8 (IL-8) were measured in all participants. Correlation between FC values and IL-6 and IL-8 levels in BD was calculated.Results Compared with the HCs, BD II patients showed decreased FC in the left orbitofrontal cortex (OFC) implicating the limbic network and the right precentral gyrus implicating the somatomotor network (SMN). BD II showed increased IL-6 (P = 0.039), IL-8 (P = 0.002) levels. Moreover, abnormal FC in the right precentral gyrus were inversely correlated with the IL-8 (r=-0.458, P = 0.004) levels in BD II. No significant correlation was found between FC in the left OFC and cytokines levels.Conclusions Our findings that serum IL-8 levels is associated with impaired FC in the right precentral gyrus in BD II patients suggest that inflammation might play a crucial role in brain functional abnormalities in BD.

Monoclonal antibody precision therapy targeting inflammation for bipolar disorder: a narrative review

“…Overall, most studies showed that the expression levels of proinflammatory cytokines, such as IL-1β, IL-6, TNF-α, IL-8, IL-17, IL-18, and IFN-γ, and anti-inflammatory cytokines IL-10 and IL-1RA are elevated in patients with BD. 5 , 22 – 44 Inconsistent results on IL-4 level have been obtained for patients with BD, whereas consistent results have been derived from studies on IL-1β, IL-6, and TNF-α. 5 , 6 , 24 , 25 , 27 , 32 – 41 , 45 After BD medication, the expression of proinflammatory cytokines IL-1β, IL-6, and TNF-α decreases, whereas the expression of anti-inflammatory cytokines IL-4 and IL-10 increases.…”

“… 5 , 22 – 44 Inconsistent results on IL-4 level have been obtained for patients with BD, whereas consistent results have been derived from studies on IL-1β, IL-6, and TNF-α. 5 , 6 , 24 , 25 , 27 , 32 – 41 , 45 After BD medication, the expression of proinflammatory cytokines IL-1β, IL-6, and TNF-α decreases, whereas the expression of anti-inflammatory cytokines IL-4 and IL-10 increases. 46 – 56 The relationship between BD symptomatic improvement after drug treatment and the variation trends of pro/anti-inflammatory cytokine levels suggests a connection between immune inflammation and BD.…”