Investigating phase coupling of respiratory sinus arrhythmia and slow wave sleep in obstructive sleep apnea patients with and without depression

Phase coherence (2) between respiratory sinus arrhythmia (RSA) and respiration has emerged as a promising metric for assessing the role of autonomic nervous system (ANS) activity and slow wave sleep (SWS) activities in healthy subjects. This study aims to investigate how 2 and SWS activity differ between Obstructive Sleep Apnea (OSA) patients with and without major depressive disorder (MDD) during overnight sleep and explore whether the correlation between 2 and SWS activity exists among those OSA patients compared to healthy individuals. Overnight electroencephalogram (EEG), electrocardiograms (ECG), and breathing using plethysmography were recorded from 104 subjects, including 35 healthy individuals (control), 34 OSA subjects with MDD (OSAD+) and 35 OSA subjects without MDD (OSAD+). Slow wave activity was computed by the amplitude envelope of the EEG delta-wave (0.5-4 Hz). The interbeat intervals (RRI) and respiratory movement were derived from ECG. RRI and respiration were resampled at a frequency of 10 Hz, and the band passed filtered within the range of 0.1-0.4 Hz before the Hilbert transform was used to extract instantaneous phases of the RSA and respiration. From the analytical signal of the Hilbert transform, the phase coherence (2) and amplitude of RSA (ARSA) were quantified. Additionally, the heart rate variability (HRV) features were calculated. Our results showed that overnight 2 was significantly greater, while the Low Frequency (LF) and High Frequency (HF) components of the HRV were significantly lower in OSAD+ compared to OSAD-. In addition, overnight delta-wave activity was greater in OSADcompared to both OSAD+ and control groups. Using auto- and cross-correlation analyses, we found that overnight profiles of 2 and delta-wave were correlated only in healthy individuals compared to OSAD+ and OSAD-, indicating that sleep apnea may only have an impact on this cortical-cardiorespiratory correlation rather than depression. Our findings suggest that 2 and SWS activity appear to be biomarkers for assessing depression in OSA patients, whereas their correlation pattern may serve as a marker for only OSA. This could enhance diagnostic precision and provide valuable insights into the complex physiological mechanisms underlying the corambid of OSA and MDD.