Abnormal intrinsic functional network connectivity in adolescent major depressive disorder related to severity of insomnia

Abstract

Backgrounds

Insomnia is closely associated with depression and plays a critical role in its development. Investigating insomnia-related neuroimaging changes in depression could enhance understanding of the neural mechanisms underlying depression insomnia. However, the brain network mechanism underlying the bidirectional relationship between depression and insomnia in adolescents remains unknown.

Methods

We recruited 83 drug-naïve adolescents with MDD and classified them into high- (HI-aMDD) and low-insomnia (LI-aMDD) groups based on the Hamilton Depression Rating Scale sleep subscale. Static and dynamic functional network connectivity (FNC) were analyzed in 34 HI-aMDD, 49 LI-aMDD patients, and 59 gender-matched healthy controls (HCs) using independent component analysis. Partial correlation analysis examined the links between FNC differences and clinical variables.

Results

The HI-aMDD patients showed decreased static FNC between the cerebellum network (CeN) and both the dorsal attention (DAN) and frontoparietal networks (FPN) and decreased dynamic CeN-DAN/limbic FNC, compared to both HCs and LI-aMDD. The LI-aMDD patients exhibited decreased static CeN-DAN/FPN connectivity and decreased dynamic CeN-DAN connectivity compared to HCs. These network connectivity alterations were negatively related to insomnia symptoms in the aMDD group.

Conclusion

Our study revealed graded static and dynamic CeN-DAN functional connectivity associated with insomnia severity in aMDD patients. High-insomnia aMDD patients showed unique dynamic interactions between CeN and limbic network, highlighting critical neural pathways involved in depression-related insomnia. These findings suggest that cerebellum, dorsal attention and limbic networks may be specifically involved in the pathophysiology of insomnia in adolescent depression and provide new potential treatment targets.