Alterations in subgenual anterior cingulate cortex functional connectivity underlie depressive symptoms in chronic insomnia disorder

Background: Chronic insomnia disorder (CID) and depression exhibit high comorbidity, yet the underlying neurobiological mechanisms remain poorly understood. Neuroimaging meta-analyses suggest the subgenual anterior cingulate cortex (sgACC) is a key node, but the characteristics of its network connectivity in CID patients with depressive symptoms (CID-D) are unclear. Methods: This study enrolled 197 participants: 66 CID patients without depression (CID-nD), 67 CID-D patients, and 64 good sleep controls (GSC). Using resting-state functional magnetic resonance imaging (fMRI), we compared sgACC-based functional connectivity (FC) across groups. We also examined correlations between altered FC and clinical symptoms, and investigated whether altered sgACC FC mediated the relationship between insomnia severity and depressive symptoms. Results: Significant group differences in sgACC FC were found in the left inferior temporal gyrus (ITG), inferior frontal gyrus (IFGtri), right supplementary motor area (SMA), postcentral gyrus (POCG), and medial superior frontal gyrus (SFGmed). Specifically, compared to CID-nD, CID-D patients showed increased FC with ITG.L and IFGtri.L, and decreased FC with SMA.R and POCG.R. FC between sgACC and ITG.L or IFGtri.L was positively correlated with depressive symptoms, while sgACC-POCG.R FC was negatively correlated. Mediation analysis revealed that sgACC-ITG.L FC partially mediated the link between insomnia and depressive symptoms. Conclusion: Our findings identify specific alterations in sgACC functional network in CID patients with comorbid depression. The mediating role of sgACC-ITG.L connectivity highlights a potential neural pathway through which insomnia contributes to depressive symptoms, identifying a putative target for neuromodulation therapies.