Altered dynamic functional connectivity in antagonistic state in first-episode, drug-naïve patients with major depressive disorder.

Objective: Major depressive disorder (MDD) is known to be characterized by disrupted brain functional network connectivity (FNC) patterns, while the dynamic change mode of different functional networks is unclear. This study aimed to characterize specific dynamic alterations pattern on intrinsic FNC in MDD by combining static FNC (sFNC) and dynamic FNC (dFNC).

Methods: A total of 48 first-episode drug-naïve MDD and 48 matched healthy controls (HCs) were included in this study. The sFNC and dFNC were analyzed using complete time-series and sliding window approach, respectively. Both sFNC and dFNC differences between groups were analyzed and associations between disease severity and aberrant FNC were explored.

Results: MDD patients exhibited lower sFNC within and between sensory and motor networks than HC. Four dFNC states were identified, including a globally-weakly-connected state, a cognitive-control-dominated state, a globally-positively-connected state, and an antagonistic state. The antagonistic state was marked by strong positive connections within the sensorimotor domain and their anti-correlations with the executive-motor control domain. Notably, MDD patients exhibited significantly longer dwell time in the globally-weakly-connected state, at the cost of significantly shorter dwell time in the antagonistic state. Further, only the mean dwell time of this antagonistic state was significantly anticorrelated to disease severity measures.

Conclusions: Our study highlights the altered dynamics of the antagonistic state as a fundamental aspect of disrupted FNC in early MDD.