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Cited by 408Stress Responses and CortisolSleep and Wakefulness ResearchCircadian rhythm and melatonin

Impact of Sleep and Its Disturbances on Hypothalamo-Pituitary-Adrenal Axis Activity

Open access
Balbo, Marcella, Leproult, Rachel, Van Cauter, Eve·2010·International Journal of Endocrinology
DOI 10.1155/2010/759234PMC PMC2902103
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Abstract

The daily rhythm of cortisol secretion is relatively stable and primarily under the influence of the circadian clock. Nevertheless, several other factors affect hypothalamo-pituitary-adrenal (HPA) axis activity. Sleep has modest but clearly detectable modulatory effects on HPA axis activity. Sleep onset exerts an inhibitory effect on cortisol secretion while awakenings and sleep offset are accompanied by cortisol stimulation. During waking, an association between cortisol secretory bursts and indices of central arousal has also been detected. Abrupt shifts of the sleep period induce a profound disruption in the daily cortisol rhythm, while sleep deprivation and/or reduced sleep quality seem to result in a modest but functionally important activation of the axis. HPA hyperactivity is clearly associated with metabolic, cognitive and psychiatric disorders and could be involved in the well-documented associations between sleep disturbances and the risk of obesity, diabetes and cognitive dysfunction. Several clinical syndromes, such as insomnia, depression, Cushing's syndrome, sleep disordered breathing (SDB) display HPA hyperactivity, disturbed sleep, psychiatric and metabolic impairments. Further research to delineate the functional links between sleep and HPA axis activity is needed to fully understand the pathophysiology of these syndromes and to develop adequate strategies of prevention and treatment.

AI snapshot

Written from the paper’s full text.

TL;DR

This review summarizes evidence that sleep has modest but detectable modulatory effects on hypothalamo-pituitary-adrenal (HPA) axis activity, with sleep onset inhibiting cortisol and awakenings stimulating it. It argues that sleep loss, shifted sleep, and sleep disruption can activate the HPA axis and that HPA hyperactivity is linked with insomnia, depression, Cushing's syndrome, and sleep disordered breathing.

Key findings

  • Sleep onset exerts a modest inhibitory effect on cortisol lasting 1–2 hours, while nocturnal awakenings transiently elevate cortisol and final morning awakening produces a rapid rise persisting about one hour.
  • Abrupt 8-hour sleep-wake delays profoundly disrupt the 24-hour cortisol rhythm: on the first shifted day, the quiescent period was reduced by more than 3 hours, relative amplitude fell by approximately 40%, and the acrophase was delayed by about 3 hours 30 minutes; by day 5 the profile had essentially adapted.
  • An 8-hour advance shifted the nadir by about 3 hours 20 minutes and reduced the quiescent period mainly via an advance of its offset by more than 3 hours, with the rising phase lengthened by nearly 3 hours and no shift in acrophase.
  • Partial sleep restriction elevated evening cortisol: after 6 nights of 4 hours in bed in 11 young men, the quiescent period onset was delayed by nearly 1.5 hours and salivary free cortisol decline from 16:00 to 21:00 was about six times slower than when fully rested; after only 1 night of 4 hours in bed, plasma cortisol over 18:00–23:00 was 37% higher and quiescent onset occurred 1 hour later.

Methods

  • Narrative review of human and animal studies on sleep, sleep disturbances, and HPA axis activity, including experimental protocols such as constant routine, shifted sleep, ultradian schedules, total sleep deprivation, partial sleep restriction, sleep-stage suppression, and sleep fragmentation.
  • Synthesizes findings from clinical syndromes including insomnia, major depression, Cushing's syndrome, and sleep disordered breathing/obstructive sleep apnea, with cited sample sizes and outcomes where reported.
  • No primary data collection or new statistical analysis is reported; the paper is a qualitative synthesis of the literature.

Limitations

  • The paper states that further research is needed to delineate functional links between sleep and HPA axis activity and to understand the pathophysiology of associated syndromes.
  • It explicitly notes contradictory findings and methodological limitations in sleep-deprivation and SDB studies, including small sample sizes, variable sleep-recording hours, variable SDB severity, single-time-point cortisol measures, and variable CPAP compliance.
  • Evident from the text: as a narrative review, it does not describe a systematic search strategy, formal quality assessment, or quantitative meta-analysis.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.1155/2010/759234

Cites

150 of 150 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

0 of 116 cited sources checked · 0 supported · 0 flagged

  • Findingcitation

    The rate of decrease of free cortisol concentrations in saliva between 16.00 hours and 21.00 hours was about six times slower in the sleep-debt than in the fully rested condition.

    “In addition, the rate of decrease of free cortisol concentrations in saliva between 16.00 hours and 21.00 hours was about six times slower in the sleep-debt than in the fully rested condition.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [83] source

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  • Findingcitation

    Some authors have reported no change or even a slight decrease in cortisol levels after one or several nights of total sleep deprivation.

    “Indeed, some authors have reported no change [41, 43, 74, 75] or even a slight decrease in cortisol levels [76, 77] after one or several nights of total sleep deprivation.”
    Quote in the paperNot a substantial claim0 of 6 sources checked
    • cites [41] 1992, Sleep source

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    • cites [43] source

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    • cites [74] 1972, Diseases of the Nervous System

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    • cites [75] 1994, Journal of Clinical Investigation source

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    • cites [76] 1980, Sleep source

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    • cites [77] 1984, Sleep source

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  • Findingcitation

    In some studies cortisol secretion seemed to be almost unaffected by recovery sleep following prolonged wakefulness.

    “while in some studies cortisol secretion seemed to be almost unaffected by recovery sleep following prolonged wakefulness [78–80]”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [78] 1989, FASEB Journal source

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    • cites [79] 1994, Journal of Clinical Endocrinology and Metabolism

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    • cites [80] source

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  • Findingcitation

    Cortisol evening levels observed under 8-hour bedtime condition were intermediate between those measured under 4-hour and 12-hour bedtime conditions.

    “Interestingly, cortisol evening levels observed under 8-hour bedtime condition were intermediate between those measured under 4-hour and 12-hour bedtime conditions [84] (Figure 5).”
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    • cites [84] source

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  • Findingcitation

    No significant changes in cortisol profiles were found in the two studies that examined the impact of SWS suppression on temporal profiles of cortisol secretion.

    “No significant changes in cortisol profiles were found.”
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    • cites [90] 1988, Psychoneuroendocrinology source

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    • cites [91] source

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  • May combine two claims. 32
  • Classified as probably not a substantial claim. 8

  • May combine two claims.

    Findingcitation

    The state of sleep debt, as compared to the fully rested state, was associated with elevated cortisol concentrations in the afternoon and in the early evening and with a shorter quiescent period, due to a delay in its onset by nearly 1.5 hour.

    “The state of sleep debt, as compared to the fully rested state, was associated with elevated cortisol concentrations in the afternoon and in the early evening and with a shorter quiescent period, due to a delay in its onset by nearly 1.5 hour.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [83] source

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    Findingcitation

    Following 2 nights of experimental sleep fragmentation across all stages, an increase in morning cortisol levels was observed, in association with a shift in the sympatho-vagal balance towards an increase of sympathetic nervous system activity, and a decrease in insulin sensitivity.

    “Following 2 nights of experimental sleep fragmentation across all stages, an increase in morning cortisol levels was observed, in association with a shift in the sympatho-vagal balance, estimated from the analysis of the heart rate variability towards an increase of sympathetic nervous system activity, and a decrease in insulin sensitivity.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [93] source

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    Findingcitation

    Several studies have reported an elevation of cortisol levels both during the night of total sleep deprivation and, if wakefulness was further prolonged, during the following day, particularly in the afternoon and evening.

    “Several studies have reported an elevation of cortisol levels both during the night of total sleep deprivation [13, 35, 72] and, if wakefulness was further prolonged, during the following day, particularly in the afternoon and evening [63, 73].”
    Quote in the paperNot a substantial claim0 of 5 sources checked
    • cites [13] 1995, Sleep

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    • cites [35] 1983, Journal of Clinical Endocrinology and Metabolism source

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    • cites [72] 1996, Journal of Pineal Research source

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    • cites [63] source

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    • cites [73] 1997, Sleep

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  • May combine two claims.

    Findingcitation

    Short sleep duration was associated with an acute increased cortisol awakening response and both short sleep duration and disturbances were independently associated with a slower rate of decline of cortisol levels across the day and thus with increased evening levels.

    “Short sleep duration was associated with an acute increased cortisol awakening response and both short sleep duration and disturbances were independently associated with a slower rate of decline of cortisol levels across the day and thus with increased evening levels.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [85] source

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  • May combine two claims.

    Findingreasoning

    Despite a relatively fast adaptation of some circadian markers, the lack of adaptation of acrophase, the longer duration of the rising phase, and the shorter duration of the quiescent period resulted in elevated cortisol levels at the time of the usual trough of the profile.

    “Therefore, despite a relatively fast adaptation of some circadian markers, the lack of adaptation of acrophase, the longer duration of the rising phase, and the shorter duration of the quiescent period resulted in elevated cortisol levels at the time of the usual trough of the profile.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingcitation

    Vgontzas et al. found a significant decrease in plasma cortisol levels, that appeared to be negatively correlated with the rebound increase of SWS.

    “Vgontzas et al. [81] found a significant decrease in plasma cortisol levels, that appeared to be negatively correlated with the rebound increase of SWS.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [81] source

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    Findingcitation

    Plasma cortisol levels over the 1800-2300 hour period were 37% higher on the day following the night of restricted sleep than on the previous day, and the onset of the quiescent period occurred 1 hour later.

    “In this study, plasma cortisol levels over the 1800–2300 hour period were 37% higher on the day following the night of restricted sleep than on the previous day, and the onset of the quiescent period occurred 1 hour later.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [73] 1997, Sleep

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    Premisecitation

    There is an excitatory reciprocal interaction between the HPA axis and the brainstem sympathetic locus coeruleus-norepinephrine system: CRH activates the LC, and NE activates hypothalamic CRH.

    “An important interplay is also the excitatory reciprocal interaction between the HPA axis and the brainstem sympathetic locus coeruleus (LC)-norepinephrine (NE) system: CRH activates the LC; in turn, NE, a known wake-promoting neurotransmitter, activates hypothalamic CRH [9, 10].”
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    • cites [9] source

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    • cites [10] source

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  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Circadian rhythms are generated by the endogenous master pacemaker in the suprachiasmatic nucleus and are entrained by environmental timing cues, most importantly light signaled via the retinohypothalamic tract.

    “Circadian rhythms are generated by the endogenous master pacemaker located in the paired suprachiasmatic nucleus (SCN) of the hypothalamus and are kept entrained to the local conditions by environmental timing cues; the most important of these cues is light, that signaled to the SCN by direct input from the retina via the retinohypothalamic tract [1].”
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    • cites [1] source

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  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Interpretationreasoning

    The daylong cortisol decline may represent the rate of recovery of the axis from the endogenous challenge.

    “The daylong cortisol decline may represent the rate of recovery of the axis from this endogenous challenge.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Awakenings and sleep offset are accompanied by cortisol stimulation.

    “awakenings and sleep offset are accompanied by cortisol stimulation”
    • Also stated in: § 3.1. Impact of Sleep Onset and Offset · boosted
      “An influence of sleep-wake transitions on cortisol secretion is also detectable during nocturnal awakenings which are consistently associated with a transient elevation of cortisol levels, followed by temporary inhibition of cortisol secretion [38].”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [38] source

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    • cites [39] source

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    Premisecitation

    Circadian oscillators are present in peripheral tissues such as liver, heart, lung, skeletal muscle, and adrenal glands.

    “circadian oscillators have been found in a number of peripheral tissues, such as liver, heart, lung, skeletal muscle, and adrenal glands [2, 3].”
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    Premisecitation

    The HPA axis receives relevant feedback from other brain areas, such as the hippocampus and amygdala.

    “In addition, the HPA axis receives relevant feedback from other areas of the brain, such as the hippocampus and amygdala [8].”
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    Interpretationcitation

    The late night rise in cortisol appears to dampen amygdala-dependent emotional processing and could exert a protective function by preventing excessive emotionality in memory.

    “Thus, the late night rise in cortisol appears to dampen amygdala-dependent emotional processing and could exert a protective function by preventing excessive emotionality in memory.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [58] source

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    Premisereasoning

    On the first day after the shift, both a higher nadir value and a lower acrophase value were observed.

    “Both a higher nadir value, due to the lack of the inhibitory effect of sleep onset, and a lower acrophase value, due to the lack of the stimulatory effect of awakening, were observed.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [67] 2000, Sleep

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    Premisecitation

    Greater age is associated with more irregular patterns of cortisol, but not ACTH secretion.

    “ApEn analysis revealed that greater age is associated with more irregular patterns of cortisol, but not ACTH secretion”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [33] 1998, European Journal of Endocrinology source

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    Premisecitation

    On the third day after the shift, the circadian onset of cortisol was delayed by more than 5 hours, while the timing of the acrophase was delayed by more than 6 hours.

    “On the third day, as a sign of partial adaptation to the new schedule, the circadian onset of cortisol was delayed by more than 5 hours, while the timing of the acrophase was delayed by more than 6 hours.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [67] 2000, Sleep

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    Premisecitation

    In the cortisol profile, the end of the quiescent period and the onset of the daily rise are mostly under the control of circadian rhythmicity, while the timing of the acrophase and the amplitude of the diurnal variation are more influenced by sleep-wake transitions.

    “In the cortisol profile, the end of the quiescent period and the onset of the daily rise are mostly under the control of circadian rhythmicity, while the timing of the acrophase and the amplitude of the diurnal variation are more influenced by sleep-wake transitions.”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [14] 1981, Journal of Clinical Endocrinology and Metabolism source

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    • cites [66] 1989, Science source

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    Premisecitation

    Mean ACTH concentrations, basal and pulsatile ACTH secretion directly correlate with BMI and are higher in men than in women, after controlling for BMI.

    “In this study, mean ACTH concentrations, basal and pulsatile ACTH secretion directly correlated with BMI and were higher in men than in women, after controlling of BMI.”
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    • cites [32] source

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    Premisecitation

    In men, ACTH-cortisol feedforward synchrony and cortisol-ACTH feedback synchrony both decline with age.

    “In addition, in men, ACTH-cortisol feedforward synchrony and cortisol-ACTH feedback synchrony both decline with age, as quantified by cross-ApEn, denoting a deterioration of coordinate control of ACTH and cortisol secretion patterns.”
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    • cites [32] source

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  • Probably not a substantial claim: may not pass S1 (asserted), S3 (load-bearing).

    Interpretationreasoning

    A functional link between the regulatory mechanisms controlling HPA activity and the level of central arousal has been hypothesized.

    “Given that high-frequency EEG over 20 Hz is considered a marker of daytime arousal [64], a functional link between the regulatory mechanisms controlling the HPA activity and the level of central arousal has been hypothesized.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [64] 2000, NeuroReport source

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  • May combine two claims.

    Premisecitation

    In young adulthood, women have lower 24-hour mean cortisol levels, a longer quiescent period, a lower acrophase, and a lower absolute amplitude of the circadian variation compared to men.

    “In young adulthood, women appeared to have, compared to men, lower 24-hour mean cortisol levels, a longer quiescent period (that started earlier and ended later), a lower acrophase, and a lower absolute amplitude of the circadian variation.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [31] source

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    Premisecitation

    The timing of the nadir and of the onset of the nocturnal cortisol rise are advanced in older adults of both sexes, and the circadian amplitude, when expressed as a percentage of the 24-hour mean level, is decreased.

    “In addition, the timing of the nadir and of the onset of the nocturnal cortisol rise are advanced in older adults of both sexes and the circadian amplitude, when expressed as a percentage of the 24-hour mean level, is decreased”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [31] source

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    Premisecitation

    During the second postshift period after the advance, there was no further advance of the timing of the nadir and only a minor additional advance of the onset of the quiescent period.

    “During the second postshift period (day 3), minor signs of further adaptation of the cortisol profiles were detected: there was no further advance of the timing of the nadir and only a minor additional advance of the onset of the quiescent period.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [68] 2002, American Journal of Physiology source

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    Premisecitation

    Metyrapone suppressed cortisol concentrations, especially the rise in cortisol during late sleep, decreased time spent in SWS, which was replaced by shallow NREM sleep, and preserved REM sleep.

    “Metyrapone suppressed cortisol concentrations, especially the rise in cortisol during late sleep, and decreased time spent in SWS, which was replaced by shallow NREM sleep. REM sleep was preserved.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [58] source

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    Premisecitation

    While memory for neutral texts was reduced, metyrapone amplified emotional enhancement in text recall.

    “While memory for the neutral texts was reduced, interestingly metyrapone even amplified emotional enhancement in text recall”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [58] source

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    Premisecitation

    On the first day after an abrupt 8-hour delay of the sleep-wake cycle, a reduction of more than 3 hours in the duration of the quiescent period resulted in an increase of the 24-hour mean cortisol levels and in the advance of the circadian onset.

    “On the first day after the shift, profound disruptions in the 24-hour cortisol rhythm were found: a reduction of more than 3 hours in the duration of the quiescent period resulted in an increase of the 24-hour mean levels and in the advance of the circadian onset.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [67] 2000, Sleep

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  • May combine two claims.

    Premisecitation

    In the first postshift period after an acute 8-hour advance of the rest-activity cycle, the timing of the nadir was advanced by about 3 hours and 20 minutes, and the quiescent period was markedly reduced mainly due to an advance of the offset by more than 3 hours.

    “In the first postshift period, compared with the baseline profile, the timing of the nadir was advanced by about 3 hours and 20 minutes; the quiescent period was markedly reduced mainly due to an advance of the offset by more than 3 hours.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [68] 2002, American Journal of Physiology source

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  • May combine two claims.

    Premisecitation

    Aging is associated, in both sexes, with a progressive increase of 24-hour mean cortisol levels from the 2nd to the 8th decade, a shorter quiescent period, and higher nadir values.

    “In the same study, aging was associated, in both sexes, with a progressive increase of 24-hour mean levels from the 2nd to the 8th decade, associated with a shorter quiescent period and higher nadir values.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [31] source

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    Premisecitation

    Retention of declarative memory critically depends on the integrity of the hippocampus and benefits specifically from early nocturnal sleep, in which SWS predominates and cortisol concentrations are minimal.

    “Retention of declarative memory critically depends on the integrity of the hippocampus and has been shown to benefit specifically from early nocturnal sleep, in which SWS predominates and cortisol concentrations are minimal [52, 53].”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [52] 1992, Psychological Review source

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    • cites [53] 1997, Journal of Cognitive Neuroscience source

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  • May combine two claims.

    Premisecitation

    In the first postshift period after the advance, no shift in the timing of the acrophase occurred, and the duration of the rising phase of cortisol secretion was increased by nearly 3 hours and presented a biphasic pattern.

    “No shift in the timing of the acrophase occurred, thus the duration of the rising phase of cortisol secretion was increased by nearly 3 hours and presented a biphasic pattern.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [68] 2002, American Journal of Physiology source

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  • May combine two claims.

    Interpretationcitation

    A biphasic HPA response to sleep deprivation has been suggested, where activation of the HPA axis, as part of the stress response, may be one of the arousal mechanisms recruited early on to adapt to sleep loss; however, when wakefulness is prolonged, the increased sleep pressure may eventually cause a blunting of the HPA axis activity.

    “Hence, a biphasic HPA response to sleep deprivation has been suggested [63] where activation of the HPA axis, as part of the stress response, may be one of the arousal mechanisms recruited early on to adapt to sleep loss; however, when wakefulness is prolonged, the increased sleep pressure may eventually cause a blunting of the HPA axis activity.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [63] source

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  • May combine two claims.

    Interpretationcitation

    The findings of high glucocorticoid levels in a condition of acute sleep loss have been interpreted as reflecting the stress of the effort to maintain wakefulness and are consistent with the positive correlation found between high frequency EEG activity in wake, indices of arousal, and cortisol release.

    “The findings of high glucocorticoid levels in a condition of acute sleep loss have been interpreted as reflecting the stress of the effort to maintain wakefulness and is consistent with the positive correlation found between high frequency EEG activity in wake, indices of arousal, and cortisol release [63].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [63] source

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  • May combine two claims.

    Interpretationreasoning

    Even if modest, the elevation in evening cortisol may result, under conditions of chronic sleep loss, in a significant glucocorticoid overload and consequently expose the body to the central and peripheral deleterious effects associated with glucocorticoid excess.

    “Even if modest, this elevation may result, under conditions of chronic sleep loss, in a significant glucocorticoid overload and consequently expose the body to the central and peripheral deleterious effects associated with glucocorticoid excess.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    There is strong evidence that elevated CRH tone increases sleep EEG frequency, thereby decreasing SWS, and increasing light sleep and wakefulness.

    “there is in turn strong evidence that elevated CRH tone increases sleep EEG frequency, thereby decreasing SWS, and increasing light sleep and wakefulness [94].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [94] 1988, Neuroendocrinology source

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  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Recurrent partial sleep restriction has become a widespread habit in modern society.

    “Recurrent partial sleep restriction has become a widespread habit in modern society [82]”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [82] 2005, Morbidity and Mortality Weekly Report

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  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Interpretationreasoning

    Findings of decreased cortisol levels after sleep deprivation have been interpreted as related to an increase in fatigue and sleepiness.

    “Findings of decreased cortisol levels after sleep deprivation have been interpreted as related to an increase in fatigue and sleepiness.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationreasoning

    Discrepancies in cortisol findings after total sleep deprivation could be due to a lack of control of experimental conditions, such as physical activity and posture, and/or to an insufficient frequency of blood sampling; short naps may have gone undetected and estimation of cortisol levels with infrequent blood sampling are often inaccurate.

    “These discrepancies could be due to a lack of control of experimental conditions, such as physical activity and posture, and/or to an insufficient frequency of blood sampling; indeed, short naps may have gone undetected and estimation of cortisol levels with infrequent blood sampling are often inaccurate.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Interpretationreasoning

    The timing of the period of recovery sleep is likely to have played a role in these conflicting findings.

    “The timing of the period of recovery sleep is likely to have played a role in these conflicting findings.”
    Quote in the paperNot a substantial claim
39 of 39

  • The paper relies on this without support.

    HPA hyperactivity is clearly associated with metabolic, cognitive and psychiatric disorders.

    “HPA hyperactivity is clearly associated with metabolic, cognitive and psychiatric disorders”

  • The paper relies on this without support.

    Several clinical syndromes, such as insomnia, depression, Cushing's syndrome, and sleep disordered breathing, display HPA hyperactivity, disturbed sleep, psychiatric and metabolic impairments.

    “Several clinical syndromes, such as insomnia, depression, Cushing's syndrome, sleep disordered breathing (SDB) display HPA hyperactivity, disturbed sleep, psychiatric and metabolic impairments.”

  • The paper relies on this without support.

    Sleep onset exerts a modest but clearly detectable inhibitory effect on the activity of the HPA axis.

    “Given the modest but clearly detectable inhibitory effect exerted by sleep onset on the activity of the HPA axis, it has been hypothesized that sleep loss might increase cortisol levels.”
3 of 3

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Various doses of recovery sleep (0, 2, 4, 6, 8, and 10 h) following five nights of experimental sleep restriction resulted in a sleep-dose-dependent decrease of lapses in the psychomotor vigilance test.

    “various doses of recovery sleep (0, 2, 4, 6, 8, and 10 h) following five nights of experimental sleep restriction resulted in a sleep-dose-dependent decrease of lapses (i.e., reaction times over 500 ms) in the psychomotor vigilance test”

    From The Sleep-Immune Crosstalk in Health and Disease (2019) · cites this paper as [28]

  • Performance did not return to baseline levels after a single night with a 10-h sleep opportunity or three nights with an 8-h sleep opportunity, suggesting that a longer recovery sleep period is needed to fully resolve performance decrements due to experimental sleep deficiency.

    “performance did not return to baseline levels after a single night with a 10-h sleep opportunity (28) or three nights with an 8-h sleep opportunity (32), suggesting that a longer recovery sleep period is needed to fully resolve any performance decrements due to experimental sleep deficiency”

    From The Sleep-Immune Crosstalk in Health and Disease (2019) · cites this paper as [28]

Cites

Flagged first, then by citations

5 of the 155 references couldn’t be matched to a known paper.

Research works printed but not linked: 19

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  2. 1998, Hormone and Metabolic Research, 30, 311
  3. 2000, American Journal of Physiology, 279, R1357
  4. 1974, Journal of Clinical Endocrinology and Metabolism, 38, 1018, 10.1210/jcem-38-6-1018 · DOI · Paper page
  5. 1985, Journal of Endocrinological Investigation, 8, 381, 10.1007/bf03348519 · DOI · Paper page
  6. 2004, Current Opinion in Neurobiology, 26, 221
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Authors
Balbo, M., Leproult, R., & Van Cauter, E.
Affiliations
  • University of Chicago (US)
  • Sleep, Chronobiology and Neuroendocrinology Research Laboratory, Department of Medicine, The University of Chicago, Chicago, IL 60637, USA
ORCID
Leproult, Rachel
Venue
International Journal of Endocrinology
Publisher
Wiley
Published
2010
Volume
2010
Pages
1-16
ISSN
  • 1687-8337 (ISSN-L)
  • 1687-8345
DOI
10.1155/2010/759234
PMC
PMC2902103
OpenAlex
W2013718939
Semantic Scholar
222089b5db5564615cd54a1b79fae94417205c62
Cited by
408
References
155
Citations by year
2026: 50 · 2025: 43 · 2024: 40 · 2023: 31 · 2022: 26 · 2021: 32 · 2020: 19 · 2019: 22 · 2018: 24 · 2017: 17 · 2016: 14 · 2015: 21 · 2014: 16 · 2013: 17 · 2012: 20
FWCI
7.30
Type
journal article
Language
en
Open access
Licence
Locations
  • International Journal of Endocrinology (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Dépôt institutionnel de l'Université libre de Bruxelles (Université Libre de Bruxelles) (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Topics
  • Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Sleep and Wakefulness Research
  • Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
Keywords
sleep, sleep disorders, hypothalamic-pituitary-adrenal axis, cortisol secretion, circadian rhythm, sleep deprivation, sleep quality, insomnia, depression, Cushing's syndrome, sleep-disordered breathing, obesity, diabetes mellitus, cognitive impairment

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-10.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-10.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

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