Dynamic functional connectivity brain state dynamics and topological organization in major depressive disorder,...

Altered functional connectivity dynamics are observed in major depressive disorder (MDD), anxiety disorders (ANX), and childhood trauma (CT), but their combined impact remains unclear. Given their frequent co-occurrence and potential shared neural mechanisms, this study examines connectivity state dynamics and spatial organization in individuals with MDD and/or ANX, with an additional focus on CT.

Resting-state fMRI data were acquired from 150 individuals with MDD and/or ANX (N = 86 with CT, N = 64 without CT) and 57 non-affected controls. Functional connectivity states were identified using k-means clustering on edge time-series. State dynamics (total transitions, fractional occupancy) and topological characteristics (mean connectivity, eigenvector centrality, modularity, global efficiency) were compared between groups (MDD/ANX vs. controls; MDD/ANX + CT vs. MDD/ANX-noCT vs. controls).

Four connectivity states were identified. No group differences in state dynamics were observed. However, MDD/ANX individuals exhibited altered topology in the weakly connected state (state 3), with reduced modularity and increased global efficiency compared to controls. In the sensory processing state (state 2), MDD/ANX + CT individuals showed lower SMN centrality compared to controls but not MDD/ANX-noCT, although this effect disappeared in a sensitivity analysis excluding controls with CT. No significant associations were found with depression, anxiety, or CT severity.

Altered topological organization reflecting less functional segregation in specific connectivity states was observed in MDD/ANX, suggesting impaired information processing. No distinct differences emerged between clinical groups with and without CT, suggesting that the observed alterations primarily reflect effects of MDD/ANX rather than CT status.