Adverse effects of two nights of sleep restriction on the hypothalamic-pituitary-adrenal axis in healthy men.
BACKGROUND
Insufficient sleep is associated with increased cardiometabolic risk. Alterations in hypothalamic-pituitary-adrenal axis may underlie this link.


OBJECTIVE
Our objective was to examine the impact of restricted sleep on daytime profiles of ACTH and cortisol concentrations.


METHODS
Thirteen subjects participated in 2 laboratory sessions (2 nights of 10 hours in bed versus 2 nights of 4 hours in bed) in a randomized crossover design. Sleep was polygraphically recorded. After the second night of each session, blood was sampled at 20-minute intervals from 9:00 am to midnight to measure ACTH and total cortisol. Saliva was collected every 20 minutes from 2:00 pm to midnight to measure free cortisol. Perceived stress, hunger, and appetite were assessed at hourly intervals by validated scales.


RESULTS
Sleep restriction was associated with a 19% increase in overall ACTH levels (P < .03) that was correlated with the individual amount of sleep loss (rSp = 0.63, P < .02). Overall total cortisol levels were also elevated (+21%; P = .10). Pulse frequency was unchanged for both ACTH and cortisol. Morning levels of ACTH were higher after sleep restriction (P < .04) without concomitant elevation of cortisol. In contrast, evening ACTH levels were unchanged while total and free cortisol increased by, respectively, 30% (P < .03) and 200% (P < .04). Thus, the amplitude of the circadian cortisol decline was dampened by sleep restriction (-21%; P < .05). Sleep restriction was not associated with higher perceived stress but resulted in an increase in appetite that was correlated with the increase in total cortisol.


CONCLUSIONS
The impact of sleep loss on hypothalamic-pituitary-adrenal activity is dependent on time of day. Insufficient sleep dampens the circadian rhythm of cortisol, a major internal synchronizer of central and peripheral clocks.
Université Claude Bernard Lyon 1 Unité Mixte de Recherche 1028 (A.G., K.S.), Integrated Physiology and Physiology of Brain Arousal Systems, 69008 Lyon, France; Endocrinologia e Malattie Metaboliche (M.B.), Azienda Sanitaria Ospedaliera Santi Antonio e Biagio e Cesare Arrigo, Alessandria, 15100 Italy; Sleep, Metabolism, and Health Center (L.L.M., E.T., R.L., E.V.C.), Department of Medicine, University of Chicago, Chicago, Illinois 60637; Neuropsychology and Functional Neuroimaging Research Unit at the Center for Research in Cognition and Neurosciences and the ULB Neuroscience Institute (R.L.), Université Libre de Bruxelles, Brussels, 1050 Belgium and Faculté de Médecine (M.L.-B.), Université Libre de Bruxelles, Brussels, 1070 Belgium.
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Guyon
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Balbo
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Morselli
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Tasali
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Leproult
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L'Hermite-Balériaux
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Van Cauter
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Spiegel
D000324:Adrenocorticotropic Hormone / Q000097:blood; D000328:Adult; D002940:Circadian Rhythm; D018592:Cross-Over Studies; D006262:Health; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D007030:Hypothalamo-Hypophyseal System / Q000378:metabolism / Q000503:physiopathology*; D008297:Male; D010913:Pituitary-Adrenal System / Q000378:metabolism / Q000503:physiopathology*; D012890:Sleep / Q000502:physiology; D012892:Sleep Deprivation / Q000378:metabolism / Q000503:physiopathology*; D013997:Time Factors; D055815:Young Adult
D000324:Adrenocorticotropic Hormone; D006854:Hydrocortisone