ABSTRACT
Background: Gender differences in hippocampal and parahippocampal gyrus (HIP/PHG) volumes have been reported in sleep disorders. Therefore, this study investigated the moderating effect of gender on the relationship between chronic insomnia disorder (CID) and the HIP/PHG functional connectivity (FC) network. Methods: For this study, 110 patients diagnosed with CID (43 men and 67 women) and 60 matched good sleep control (GSC) (22 men and 38 women) were recruited. These participants underwent resting-state functional magnetic resonance imaging scans, after which a 2 × 2 (diagnosis × gender) analysis of variance was used to detect the main and interactive effect of insomnia and gender on their HIP/PHG FC networks. Results: Although the main effect of insomnia on the HIP FC network was observed in the bilateral cerebellar tonsil, superior frontal gyrus, and the medial orbitofrontal cortex, effects on the PHG FC network were observed in the bilateral HIP and amygdala. In contrast, the main effect of gender on the HIP FC network was observed in the right cerebellum posterior lobe, the dorsolateral prefrontal cortex (DLPFC), and the supplemental motor area. Of note, the interactive effect of both insomnia and gender was observed in FCs between the right HIP and the dorsal anterior cingulate cortex, and then between the right PHG and DLPFC. Moreover, the FC between the right PHG and left DLPFC was positively associated with anxiety scores in the female patients with CID. Conclusion: Our study identified that gender differences in brain connectivity existed between the HIP/PHG and executive control network in patients diagnosed with CID, these results will eventually extend our understanding of the important role that gender plays in the pathophysiology of CID.