Sample entropy of heart rate variability during cyclic alternating pattern in obstructive sleep apnoea with and without comorbid depression

Obstructive sleep apnoea (OSA) and major depressive disorder (MDD) frequently co-occur and both have been associated with autonomic dysregulation. Whether the co-occurrence alters the short-scale dynamical organisation of cardiac control during the cyclic alternating pattern (CAP) of NREM sleep is unknown. We retrospectively analysed overnight polysomnography from 44 adults with OSA, 18 with comorbid MDD diagnosed by psychiatrist-administered Mini-International Neuropsychiatric Interview (MINI) version 5 (OSAD+) and 26 without MDD (OSAD−) and from 10 healthy controls drawn from an institutional CAP repository. All MDD patients were antidepressant-naive at the time of PSG. After delta-band-based CAP A-phase detection on the C4–A1 EEG, we extracted 22 HRV indices spanning time, frequency (Lomb–Scargle) and nonlinear domains from RR intervals occurring inside CAP windows, and compared groups with two-tailed Mann–Whitney *U* tests, Benjamini–Hochberg FDR-corrected, supplemented by stepwise logistic regression and receiver-operating characteristic (ROC) analysis. The OSAD+ and OSAD− groups did not differ in age, sex, BMI, AHI or CAP rate. Sample entropy (SampEn) during CAP was reduced in OSAD− compared with healthy controls (0.87 ± 0.05 vs 1.05 ± 0.02, *p* = 0.004) and was *not* reduced in OSAD+ (1.00 ± 0.05; OSAD+ vs control *p* = 0.29). The OSAD+ vs OSAD− difference reached nominal significance (raw *p* = 0.043; AUC = 0.69) but did not survive correction for multiple comparisons across the 22 features (Benjamini–Hochberg-adjusted *p* = 0.83). A multivariable logistic-regression model retaining SampEn and high-frequency power (HF) achieved an AUC of approximately 0.77 and is reported as hypothesis-generating; no other linear or nonlinear HRV index distinguished the groups. In OSA, the short-scale irregularity of CAP-aligned RR intervals is reduced relative to healthy controls in the absence of MDD and is restored towards control values in the presence of comorbid MDD. The finding is exploratory and requires replication in larger cohorts with prospective insomnia screening (Insomnia Severity Index) and stratification by depression subtype, but it identifies CAP-aligned SampEn as a candidate physiological marker of the depressive phenotype within OSA and motivates a re-framing of “complexity loss” interpretations as context- and microstructure-dependent.