Major depressive disorder (MDD) is a complex mood disorder characterized by persistent and overwhelming depression. Previous studies have identified abnormalities in large scale functional brain networks in MDD, yet most of them were based on static functional connectivity. In contrast, here we explored disrupted topological organization of dynamic functional network connectivity (dFNC) in MDD based on graph theory. One hundred and eighty-two MDD patients and 218 healthy controls were included in this study, all Chinese Han people. By applying group information guided independent component analysis (GIG-ICA) to resting-state functional magnetic resonance imaging (fMRI) data, the dFNCs of each subject were estimated using a sliding window method and k-means clustering. Network properties including global efficiency, local efficiency, node strength and harmonic centrality, were calculated for each subject. Five dynamic functional states were identified, three of which demonstrated significant group differences in their percentage of state occurrence. Interestingly, MDD patients spent much more time in a weakly-connected State 2, which includes regions previously associated with self-focused thinking, a representative feature of depression. In addition, the FNCs in MDD were connected differently in different states, especially among prefrontal, sensorimotor, and cerebellum networks. MDD patients exhibited significantly reduced harmonic centrality primarily involving parietal lobule, lingual gyrus and thalamus. Moreover, three dFNCs with disrupted node properties were commonly identified in different states, and also correlated with depressive symptom severity and cognitive performance. This study is the first attempt to investigate the dynamic functional abnormalities in MDD in a Chinese population using a relatively large sample size, which provides new evidence on aberrant time-varying brain activity and its network disruptions in MDD, which might underscore the impaired cognitive functions in this mental disorder.

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