Objective: To evaluate the associations between cerebrospinal fluid orexin-A (ORX) levels and markers of nocturnal sleep stability, assessed by polysomnography (PSG).

Methods: Nocturnal PSG data and ORX levels of 300 drug-free subjects (55% men, 29.9±15.5 years, ORX level 155.1±153.7 pg/ml) with hypersomnolence were collected. Several markers of nocturnal sleep stability were analyzed: wake and sleep bouts, sleep/wake transitions. Groups were categorized according to ORX levels, in two categories (deficient≤110; >110), in tertiles (≤26, ]26;254], >254), and compared using logistic regression models. Results were adjusted for age, sex and body mass index.

Results: We found higher number of wake bouts (43 vs 25, p<0.0001), sleep bouts (43 vs 25.5, p<0.0001) and index of sleep bouts/hour of sleep time, but lower index of wake bouts/hour of waketime (41.4 vs 50.6, p<0.0001) in subjects with ORX deficiency. The percentage of wake bouts <30sec was lower (51.3 vs 60.8%, p<0.001) and of wake bouts ³1min30sec higher (7.7 vs 6.7%, p=0.02) when ORX deficient. The percentage of sleep bouts ≤14min was higher (2-5min: 23.7 vs 16.1%, p<0.0001), and of long sleep bouts lower (>32min30sec: 7.3 vs 18.3%, p<0.0001) when ORX deficient. These findings were confirmed when groups were categorized according to ORX tertiles, with a dose-response effect of ORX levels in post-hoc comparisons, and in adjusted models.

Interpretation: This study shows an association between ORX levels and nocturnal sleep stabilization in patients with hypersomnolence. Sleep and wake bouts are reliable markers of nighttime sleep stability that correlate with CSF ORX levels in a dose-dependent manner.