Insomnia severity impact dynamic connectivity and modulate connectivity-cognitive links in major depressive disorder.

BACKGROUND

Insomnia is common in major depressive disorder (MDD), and varying severity of insomnia may be associated with distinct neural alterations in MDD. Dynamic functional connectivity can capture time-varying brain network interactions and may help disentangle insomnia-related mechanisms in MDD.

METHODS

We recruited 203 drug-naïve adult MDD patients, divided into high- (HI-MDD, n = 133) and low-insomnia (LI-MDD, n = 70) groups using the Hamilton Depression Rating Scale insomnia subscale, along with 122 health controls (HCs). Independent component analysis and a sliding-window approach were applied to explore static and dynamic functional network connectivity (FNC).

RESULTS

While static FNC revealed no significant group difference, dynamic analysis identified distinct connectivity states between two groups. Compared to HCs, HI-MDD displayed more frequent occurrence of state I and less of state IV, a pattern was absent in LI-MDD. Both MDD groups showed increased default mode network (DMN)-lateral ventral attention network (VAN) connectivity in states I and II, accompanied by decreased dorsal attention network-cerebellar/DMN connectivity in state I relative to HCs. Compared with LI-MDD, HI-MDD exhibited enhanced DMN-medial VAN connectivity in state II, along with increased DMN connectivity with visual and sensorimotor networks in state I, suggesting insomnia-related changes. In addition, we identified insomnia-related memory deficits and depression-related processing speed impairment in MDD. Insomnia significantly moderated the association between altered DMN-lateral VAN connectivity in state I and logical memory impairment in MDD.

CONCLUSIONS

These findings suggest that insomnia severity in MDD is associated with distinct temporal patterns of brain network alterations beyond shared depression-related changes and moderate cognitive functions in MDD.