Functional dysconnectivity of large-scale functional brain networks in young adults with bipolar disorder with and without low-grade inflammation.

Abstract

Bipolar disorder (BD) is associated with both functional brain network disruptions and low-grade peripheral inflammation, yet their interplay remains poorly understood. This study aimed to investigate whether low-grade inflammation is linked to altered functional connectivity across major brain networks in young individuals with BD. A total of 160 young adults with BD and 93 age-and sex-matched controls were included. Resting-state functional images were obtained using 3T magnetic resonance imaging (fMRI), and seed-based connectivity (SBC) analyses were conducted to map functional connectivity (FC) patterns with specific regions of interest (ROIs) from well-established resting-state networks, including the Default Mode Network (DMN), Salience Network (SN), Frontoparietal Network (FPN), and reward network. Fasting plasma C-reactive protein (CRP) level were measured, and low-grade inflammation (LGI) was defined based on CRP levels of ≥3 mg/L. There was a total of 27 participants with BD in the LGI group and 133 in the non-LGI group. SBC analyses showed increased FC within the SN in the LGI group compared with HCs, whereas the non-LGI group showed numerically intermediate values (e.g. ACC-precentral gyrus connectivity: LGI > non-LGI > HC, all pairwise comparisons significant). A similar pattern was observed for FC between the ventral tegmental area and the bilateral supramarginal gyrus (LGI > non-LGI > HC) within the reward network. Within the DMN, both BD groups showed decreased functional connectivity between the medial prefrontal cortex and the left putamen compared with the HC group. Low-grade inflammation is linked to distinct brain connectivity changes in young individuals with bipolar disorder, highlighting the role of neuroimmune mechanisms in its pathophysiology.