Low Sleep Quality in Major Depressive Disorder is Associated with Thinning and Decreased Functional Connectivity of the Insular Cortex

Sleep disturbances are common in depression, but their neurobiological correlates are poorly understood. Recent evidence suggests links between insula dysfunction and sleep dysregulation. This study aimed to explore the association of sleep quality and structural and functional characteristics of the insula in major depressive disorder (MDD). We included 47 patients with MDD and 15 healthy controls (HC) matched for age and sex. Sleep quality was assessed with the Pittsburgh Sleep Quality Index (PSQI). Patients were classified into two subgroups with poor sleep (PAT-PS, PSQI > 8) and normal sleep (PAT-NS, PSQI ≤ 8), respectively. MRI-scans were acquired using structural and functional resting-state sequences. We analysed cortical thickness of bilateral insulae and connectivity strength of the insula to the whole brain using intrinsic connectivity. Group differences were assessed with a mixed-model MANCOVA controlling for age and sex. Patients had higher PSQI-scores than HC. PAT-PS (n = 21) and PAT-NS (n = 26) did not differ regarding age, sex and depression severity. Insular cortical thickness was reduced in PAT-PS compared to both HC and PAT-NS. Additionally, PAT-PS had lower insular intrinsic connectivity than HC. In contrast, there were no significant group differences in insular intrinsic connectivity between PAT-NS and HC. Across all subjects, PSQI-total was negatively associated with insular cortical thickness and insular intrinsic connectivity. Insular intrinsic connectivity within patients was negatively associated with depression severity. PSQI-total and depression severity did not correlate significantly. In conclusion, our results demonstrate that sleep disturbances in MDD patients are associated with structural and functional impairments of the insula.