What question did this study set out to answer?

This study aims to investigate the association between brain network topology and inflammation in unmedicated bipolar II depression.

April 3, 2026Psychological Medicine0 citationsOpen Access

Disrupted brain functional network topology is associated with peripheral inflammation in unmedicated bipolar II depression

GTGuixian TangDongguan People’s Hospital GCGuanmao ChenJinan University PCP. ChenUniversity of Illinois Chicago

Key Points

This study aims to investigate the association between brain network topology and inflammation in unmedicated bipolar II depression.
Conducted resting-state MRI scans in 65 unmedicated individuals with bipolar II depression and 50 healthy controls.
Applied graph theory analysis to examine functional connectivity in the brain.
Measured serum levels of 17 inflammatory cytokines in both groups.
Calculated correlations between brain properties, clinical variables, and inflammatory cytokine levels.
Bipolar II depression group showed significant alterations in global network properties compared to healthy controls.
Increased levels of IL-8, IL-10, and G-CSF were observed in individuals with bipolar II depression.
Negative correlations found between certain graph metrics and depression severity scores.
IL-8 levels negatively correlated with specific nodal efficiencies in brain regions relevant to mood regulation.

Abstract

Abstract Background Increasing evidences show that inflammation might be involved in bipolar disorder (BD), but the association between abnormal brain function and inflammation in BD is still unclear. In this study, we tried to explore the disrupted brain functional network topology, peripheral inflammatory cytokine levels, and their correlations in unmedicated bipolar II depression (BDII-D). Methods In this study, 65 individuals with unmedicated BDII-D and 50 healthy controls (HCs) underwent resting-state magnetic resonance imaging scans. Graph theory analysis was performed to investigate the topological properties of the whole-brain functional connectome at both global and nodal levels. Besides, serum levels of 17 inflammatory cytokines were measured in both BDII-D and HCs. Correlations between topological properties, clinical variables, and peripheral inflammatory cytokine levels in BDII-D were calculated. Results Compared with HCs, at the global level, BDII-D showed significantly higher, decreased, , E glo, and E loc ; at the nodal level, BDII-D showed decreased E nodal in the right olfactory cortex, left pallidum, and vermis. Besides, BDII-D showed higher levels of interleukin-8 (IL-8), interleukin-10 (IL-10), and granulocyte colony-stimulating factor (G-CSF) compared with the HCs. In BDII-D, and were significantly negatively correlated with the Hamilton Depression Rating Scale (HDRS) scores and number of episodes. Also, IL-8 level showed significant negative correlation with, , and E nodal of the left pallidum in BDII-D. Conclusions Reduced information segregation and integration, and lower nodal efficiency in the left pallidum were associated with proinflammatory cytokine IL-8 level and might contribute to severe depressive symptoms in unmedicated BDII-D.

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