Neural substrates underlying REM sleep duration in patients with major depressive disorder: A longitudinal study combining multimodal MRI data

Prior studies have discussed rapid eye movement (REM) sleep disturbance as a potential endophenotype of major depressive disorder (MDD). However, the neural substrates underlying the percentage of REM sleep duration (REM%) and its association with disease progression in MDD remain unclear. One hundred and fourteen MDD patients and 74 healthy controls (HCs) underwent resting-state functional and perfusion magnetic resonance imaging (MRI) scans as well as overnight polysomnography examination to assess brain function and REM%, with 48 patients completing follow-up visits. Correlation and mediation analyses were conducted to investigate the associations among baseline REM%, multimodal brain imaging measures, and the improvement of depressive symptoms at follow-up in MDD. We found voxel-wise correlations between baseline REM% and multimodal brain imaging metrics in many brain regions involved in sensorimotor, visual processing, emotion, and cognition in patients with MDD. Moreover, the baseline REM% was correlated with the improvement of depressive symptoms from acute to remitted status in patients through regulating brain activity in the left inferior temporal gyrus and cerebral blood flow in the bilateral paracentral lobule. Our findings help to identify the neural underpinnings of REM% in depression and highlight REM% as a potential prognostic biomarker to predict disease progression. These may inform future novel interventions of MDD from the perspective of regulating REM sleep.