The brain, rapid eye movement sleep, and major depressive disorder: A multimodal neuroimaging study

Evidence has established the prominent involvement of rapid eye movement (REM) sleep disturbance in major depressive disorder (MDD). However, the neural correlates of REM sleep in MDD and their clinical significance are less clear. Cross-sectional and longitudinal polysomnography and resting-state functional MRI data were collected from 131 MDD patients and 71 healthy controls to measure REM sleep and voxel-mirrored homotopic connectivity (VMHC). Correlation and mediation analyses were performed to examine the associations between REM sleep, VMHC, and clinical variables. Moreover, we conducted spatial correlations between the neural correlates of REM sleep and a multimodal collection of reference brain maps to facilitate genetic, structural and functional annotations. MDD patients exhibited REM sleep abnormalities manifesting as higher REM sleep latency and lower REM sleep duration, which were correlated with decreased VMHC of the precentral gyrus and inferior parietal lobe and mediated their associations with more severe anxiety symptoms. Longitudinal data showed that VMHC increase of the inferior parietal lobe was related to improvement of depression symptoms in MDD patients. Spatial correlation analyses revealed that the neural correlates of REM sleep in MDD were linked to gene categories primarily involving cellular metabolic process, signal pathway, and ion channel activity as well as linked to cortical microstructure, metabolism, electrophysiology, and cannabinoid receptor. These findings may add important context to the growing literature on the complex interplay between sleep and MDD, and more broadly may inform future treatment for depression via regulating sleep. •MDD patients exhibited REM sleep abnormalities (higher REML and lower REM%).•These abnormalities were correlated with decreased VMHC.•Longitudinal VMHC alteration was related to improvement of depressive symptoms in MDD.•The neural correlates of REM sleep in MDD were linked to gene categories and structural and functional annotations.