Li G, Liu Y, Zheng Y, et al. - Spectral dynamic causal modeling was applied in order to evaluate effective connectivity (EC) of a large-scale network with 27 regions of interests from four distributed functional brain networks (default mode, executive control, salience, and limbic networks), on the basis of a large sample-size resting-state fMRI comprising of 100 healthy individuals and 100 persons with first-episode drug-naive MDD. It was exhibited that both within and between high-order functional networks, MDD modified EC. Particularly, MDD was related to decreased excitatory connectivity especially within the default mode network (DMN), and between the default mode and salience networks. Moreover, within the DMN, the network-averaged inhibitory EC was discovered to be notably increased in the MDD. The coexistence of the decreased excitatory, however, raised inhibitory causal connections within the DMNs could underlie disrupted self-identification and emotional control in MDD. In summary, this study highlights that among high-order brain functional networks, MDD could be related to modified causal interactions.