Intra- and Inter-Network Connectivity of the Default Mode Network Differentiating Treatment-Resistant Depression From Treatment-Sensitive Depression

Abstract

Background: Understanding why some patients with depression remain resistant to antidepressant medication could be elucidated by investigating the neural features of treatment resistance. Research has consistently demonstrated abnormalities in the rostral anterior cingulate cortex (rACC) - a region that is part of the default mode network (DMN) - in treatment-resistant depression (TRD). We evaluated the resting-state functional connectivity (rsFC) of the rACC with other regions of the default-mode network to better understand the role of this structure in the pathophysiology of TRD. Method(s): 35 TRD patients, 35 treatment-responsive patients (TSD), and 38 healthy controls (HC) underwent eyes-open resting-state functional MRI protocol. Seed-based functional connectivity analyses were performed, comparing the three groups for the rsFC between the rACC and the DMN (cluster-level familywise error-corrected p < 0.05, voxel-wise threshold of p < 0.001). Furthermore, inter-network connectivity of the DMN with other neural networks was explored by independent component (ICA) analyses (vertex-level threshold of p < 0.01, false-discovery rate error-corrected). Result(s): The results demonstrated hyperconnectivity between the rACC and the posterior cingulate cortex in TRD relative to TSD and HC (F(2,105)=5.335, p < 0.05). ICA also found lower connectivity between the default-mode network best-match component and the precentral gyrus, a region of the somatomotor network (F(2,105)=18.968, p < 0.000), in the TRD group compared to TSD and HC. Conclusion(s): We found intra- and inter-network connectivity abnormalities in the default-mode network in TRD. These results differentiate TRD from TSD, providing confirmatory evidence of default-mode network hyperconnectivity and preliminary evidence for its interactions with other neural networks as key neural mechanisms underlying treatment non-responsiveness.