Dynamic functional connectivity brain state dynamics and topological organization in major depressive disorder, anxiety disorder and childhood trauma

Background: 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. Methods: 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). Results: 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. Conclusion: 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.