Resting-state functional connectivity is correlated with peripheral inflammatory markers in patients with major depressive disorder and healthy controls

BACKGROUND: Recent studies have highlighted the significant role of inflammation in the development and progression of major depressive disorder (MDD). Elevated levels of proinflammatory cytokines have consistently been observed in MDD, and these markers are shown to be linked to disruptions in brain networks. Therefore, we aimed to explore the relationship between inflammatory markers and resting-state functional connectivity (RSFC) in patients with MDD. METHODS: This study included 76 patients with MDD and 92 healthy controls (HCs). Seed-to-voxel RSFC analysis was performed using brain regions that have been identified in previous studies on the neural networks implicated in MDD. These regions served as key hubs in the default mode, salience, cognitive control, and frontostriatal networks and were used as seed regions. RESULTS: Compared with HCs, patients with MDD exhibited elevated levels of interleukin (IL)-6 and IL-8. The MDD group showed significant alterations of the RSFC between the prefrontal cortex (PFC), anterior cingulate cortex, visual cortex, postcentral gyrus, and striatal regions compared to the HC group. Additionally, within the MDD group, a positive correlation was observed between tumor necrosis factor (TNF)-α levels and the RSFC of the right dorsolateral prefrontal cortex (dlPFC) and visual cortex. Conversely, in the HC group, TNF-α levels were negatively correlated with the RSFC between the right dlPFC and bilateral dorsomedial prefrontal cortex, while positive correlations were noted between the RSFC of the right dlPFC with occipital regions and the levels of both IL-8 and TNF-α. CONCLUSIONS: The present study confirmed that cytokine levels are linked to alterations in the RSFC, particularly in the prefrontal regions. Our findings suggest that systemic inflammation may contribute to functional disruptions in the brain networks involved in emotion regulation and cognitive control in MDD.