CSF Orexin-A Levels Strongly Associated With Nocturnal Sleep Fragmentation

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Researchers examined the association between orexin-A levels in CSF and traits of nocturnal sleep fragmentation, as evaluated by polysomnography, in a large cohort of adults and children with self-reported hypersomnolence.

Orexin (ORX) may play an important role in sleep characteristics in children and adults. An association between ORX-A levels in the cerebrospinal fluid (CSF) and nocturnal sleep stabilization was documented in a study presented at the World Sleep 2019 held September 20-25 in Vancouver, British Columbia.

The goal of the current study was to explore the association between ORX-A levels in CSF and nocturnal sleep fragmentation as assessed by polysomnography. The researchers focused on children and adults whose hypersomnolence was evaluated at the French National Reference Center for Narcolepsy.

The study included 300 participants (mean age, 29.9±15.6 years; 55% men) with available polysomnography data. The average ORX-A levels were 155.1±153.8 pg/mL.

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The researchers assessed several markers of nocturnal sleep fragmentation: wake bouts, transitions from sleep to wake, wake to sleep, and instability of sleep stages. Hypersomnolence was classified according to ORX-A level, initially in tertiles, and later in 2 (≤110 pg/mL or >110 pg/mL) and 4 categories (undetectable, 10-110 pg/mL, >110-200 pg/mL, >200 pg/mL).

Of the total participants, 136 had ORX >110 pg/mL and 164 had ORX deficiency (≤110 pg/mL). Those with ORX deficiency were younger, were more frequently men, had higher body mass index, had shorter total sleep time, and had longer wake time after sleep onset. Orexin deficiency was associated with a higher frequency of microarousals and a higher number of wake bouts (43 vs 25.5; P <.0001).

After classification of sleep fragmentation into 4 groups according to ORX-L levels, a dose-response effect of ORX level was found on wake bouts and other markers of sleep fragmentation. Crude and adjusted statistical models confirmed the results.

“This study provides a strong evidence of the direct effect of ORX on nocturnal sleep stabilization in humans. Sleep and wake bouts turned out to be new reliable markers of sleep fragmentation, strongly correlated to CSF ORX levels, in a dose dependent way,” concluded the researchers.


Barateau L, Lopez R, Jaussent I, Dauvilliers Y. Nocturnal sleep fragmentation and CSF orexin levels in humans: sleep and wake bouts. Abstract presented at World Sleep 2019; September 20-25, 2019; Vancouver, British Columbia, Canada.