Difference of Resting State Functional Connectivity between Depressive Patients with and without Clinically Significant Insomnia

Objective: Insomnia is a common symptom of major depressive disorder (MDD). However, the neural distinctions be tween MDD with and without insomnia remain unclear. This study investigated resting state functional connectivity (RSFC), specifically seeding the habenula and septal nuclei, to identify neurobiological abnormalities associated with insomnia in MDD. Methods: Thirty-six patients with MDD and clinically significant insomnia (MDD_w/INS), 21 patients without insomnia (MDD_wo/INS), and 38 healthy controls underwent 3T resting-state fMRI. Seed-to-voxel RSFC analyses were conducted using the habenula and septal nuclei as seeds. Between-group comparisons and correlation analyses were adjusted for age, sex, years of education, and Hamilton Depression Rating Scale 17 items (HDRS-17) scores. Results: The MDD cohort had a mean age of 35.6 years and mean illness duration of 7.3 years. Compared to the MDD_wo/INS group, the MDD_w/INS group exhibited significantly higher depressive symptom severity (HDRS-17: 19.4 ± 4.8 vs. 13.8 ± 4.3) but a shorter illness duration (6.4 ± 6.9 vs. 8.9 ± 6.8 years). RSFC was increased between the left habenula and the right Rolandic operculum and cuneus and between the right habenula and thalamic pulvinar in the MDD_w/INS group. In contrast, decreased RSFC was observed between the septal nuclei and right cerebellar Crus I. All altered RSFC patterns were significantly correlated with the severity of insomnia. Conclusion: This study reveals distinct RSFC patterns associated with insomnia in MDD, emphasizing the role of the habenula and septal nuclei and their potential significance in modulating mood and sleep patterns in MDD.