Functional connectivity of the default mode network subsystems in patients with major depressive episodes with mixed features

Background The neuroimaging mechanism of major depressive episodes with mixed features (MMF) is not clear.Aims This study aimed to investigate the functional connectivity of the default mode network (DMN) subsystems among patients with MMF and patients with major depressive disorder without mixed features (MDDnoMF).Methods This study recruited 47 patients with MDDnoMF and 27 patients with MMF from Beijing Anding Hospital, Capital Medical University, between April 2021 and June 2022. Forty-five healthy controls (HCs) were recruited. All subjects underwent resting-state functional magnetic resonance imaging scanning and clinical assessments. Intranetwork and internetwork functional connectivity were computed in the DMN core subsystem, dorsal medial prefrontal cortex (dMPFC) subsystem and medial temporal lobe (MTL) subsystem. Analysis of covariance method was performed to compare the intranetwork and internetwork functional connectivity in the DMN subsystems among the MDDnoMF, MMF and HC groups.Results The functional connectivity within the DMN core (F=6.32, pFDR=0.008) and MTL subsystems (F=4.45, pFDR=0.021) showed significant differences among the MDDnoMF, MMF and HC groups. Compared with the HC group, the patients with MDDnoMF and MMF had increased functional connectivity within the DMN MTL subsystem, and the patients with MMF also showed increased functional connectivity within the DMN core subsystem. Meanwhile, compared with the MDDnoMF, the patients with MMF had increased functional connectivity within the DMN core subsystem (mean difference (MDDnoMF−MMF)=−0.08, SE=0.04, p=0.048). However, no significant differences were found within the DMN dMPFC subsystem and all the internetwork functional connectivity.Conclusions Our results indicated abnormal functional connectivity patterns of DMN subsystems in patients with MMF, findings potentially beneficial to deepen our understanding of MMF’s neural basis.