The relationship between sleep efficiency and clinical symptoms is mediated by brain function in major depressive disorder

Background: Sleep disturbance is a common and key symptom that affects most of patients with major depressive disorder (MDD). However, neural substrates underlying sleep disturbance and their clinical relevance in depression remain unclear. Methods: Ninety-six MDD patients underwent resting-state functional MRI. Fractional amplitude of low-frequency fluctuation (fALFF) and resting-state functional connectivity (rsFC) were used to measure brain function. Overnight polysomnography was performed to objectively measure sleep efficiency (SE), which was used to classify patients into normal sleep efficiency (NSE) and low sleep efficiency (LSE) groups. Between-group differences in fALFF and rsFC were examined using two-sample t-tests. Moreover, correlation and mediation analyses were conducted to test for potential associations between SE, brain functional changes, and clinical variables. Results: LSE group showed decreased fALFF in right cuneus, thalamus, and middle temporal gyrus compared to NSE group. MDD patients with low SE also exhibited lower rsFC of right cuneus to right lateral temporal cortex, which was associated with more severe depression and anxiety symptoms. More importantly, mediation analyses revealed that the relationships between SE and severity of depression and anxiety symptoms were significantly mediated by the altered rsFC. In addition, these low SE-related brain functional alterations were not affected by antidepressant medication and were independent of structural changes. Limitations: The lack of healthy controls because of first-night effect. Conclusion: These findings not only may expand existing knowledge about neuropathology of sleep disturbance in depression, but also may inform real-world clinical practice by improving depression and anxiety symptoms through sleep regulation.