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Cited by 338Sleep and Work-Related FatigueCircadian rhythm and melatoninSleep and Wakefulness Research

Sleep Deprivation and Circadian Disruption

Open access
McEwen, Bruce S., Karatsoreos, Ilia N.·2015·Sleep Medicine Clinics
DOI 10.1016/j.jsmc.2014.11.007PMC PMC8935364
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Abstract

“Getting a good night’s sleep” seems a panacea for improving mood and cognition. These subjective impressions are supported by countless studies exploring impacts of sleep (and sleep loss) on mental health, metabolism, and immune function. Similarly, being “out of phase” with local time, commonly experienced by shift workers of jetlagged air travelers, demonstrates that there are both neural and physiologic effects of internal circadian (daily) time being misaligned with external environmental time. This chapter reviews these areas contextualized using the model of allostasis and allostatic load that emphasizes the impact of this “wear and tear” on the brain and body.

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Written from the paper’s full text.

TL;DR

This review uses the allostasis/allostatic load model to argue that sleep deprivation and circadian disruption act as chronic stressors causing “wear and tear” on the brain and body. It summarizes evidence linking these disruptions to metabolic, immune, neurobehavioral, and mood effects, including altered brain structure and increased risk of obesity, diabetes, and cardiovascular disease.

Key findings

  • Sleep deprivation produces allostatic overload: after only 4 hours, increases in blood pressure, decreases in parasympathetic tone, increases in evening cortisol, increased insulin, and increased appetite are observed; reduced sleep duration is associated with increased body mass and obesity in NHANES.
  • Circadian disruption independent of explicit sleep loss can cause metabolic and brain changes: mice housed in a 20-hour light-dark cycle for 5 weeks showed increased weight, adiposity, and leptin, an insulin/glucose imbalance suggesting a prediabetic state, shrunken and less complex apical dendrites in medial prefrontal cortex layer II/III, cognitive rigidity, and an impulsive-like phenotype.
  • Sleep deprivation and circadian disruption affect mood and immunity: acute sleep deprivation improves mood in 40% to 60% of depressed subjects within 24 to 48 hours; modest sleep restriction to 6 hours per night increases pro-inflammatory cytokines and worsens psychomotor vigilance; poor sleep in aging women is associated with elevated interleukin-6.
  • Neural effects include impaired memory and synaptic plasticity, reduced dentate gyrus cell proliferation by as much as 50% after 96 hours of treadmill sleep deprivation, decreased brain glycogen by as much as 40% after 24 hours of sleep deprivation, and, in short-recovery flight crews, shrunken medial temporal lobes, increased reaction time, poorer visual-spatial performance, and a correlation between salivary cortisol and medial temporal cortex volume.

Methods

  • Narrative review of selected literature; no primary experimental sample or new data are reported, and findings are synthesized within the allostasis/allostatic load framework.
  • Discusses specific animal models (e.g., environmental circadian desynchronization with a 20-hour light-dark cycle, chronic restraint stress, sleep deprivation by gentle handling, novelty, platform/flower pot, treadmill) and human studies (e.g., flight crews, NHANES, sleep deprivation in depression).
  • Main analysis is conceptual integration rather than systematic meta-analysis; no search strategy or quantitative synthesis is stated.

Limitations

  • Stated: the specific mechanisms by which disrupted circadian clocks cause changes in brain, behavior, and peripheral physiology remain unknown.
  • Stated: circadian models are purposefully “exotic” (e.g., shortened 20-hour days are not expected to become common in human society) and should serve as proof-of-principle for more ecologically relevant models; sleep deprivation methods can confound effects with stress or activity, and untangling sleep loss from circadian misalignment remains critical.
  • Evident: as a narrative review, it does not systematically search or select studies or quantify bias; many cited findings come from animal models and may not directly translate to humans.

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Integrity signals

Registry

Crossref · 10.1016/j.jsmc.2014.11.007

Cites

105 of 105 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

0 of 103 cited sources checked · 0 supported · 0 flagged

  • Premisereasoning

    Internal circadian time being misaligned with external environmental time has neural and physiologic effects.

    “Similarly, being “out of phase” with local time, commonly experienced by shift workers of jetlagged air travelers, demonstrates that there are both neural and physiologic effects of internal circadian (daily) time being misaligned with external environmental time.”
    Quote in the paperSubstantial claim
  • Premisecitation

    Disruption of circadian patterns of CORT by adrenalectomy and tonic replacement results in a sluggish HPA axis response with poor shutoff of ACTH after stressor termination, in contrast to diurnal CORT replacement.

    “Indeed, if circadian patterns of CORT are disrupted by adrenalectomy (ADX) and tonic replacement of CORT via a pellet implant providing no diurnal rhythm, this results in a “sluggish” HPA axis response, with poor shutoff of adrenocorticotropic hormone following termination of a stressor, in contrast to the situation in which the ADX animal drinks CORT in the water in a diurnal pattern.18”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [18] Jacobson, 1988, Circadian variations in plasma corticosterone permit normal termination of adrenocorticotropin responses to stress, Endocrinology source

      Not checked in the free run.

  • Premisecitation

    Inadequate containment of the pro-inflammatory response can lead to septic shock and death.

    “Inadequate containment can lead to septic shock and death.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [4] Munck, 1991, Glucocorticoids and immune function

      Not checked in the free run.

  • Premisenone given

    All systems that are modulators of allostasis show rhythms of activity over the sleep-wake cycle.

    “All of the systems that are modulators of allostasis show rhythms of activity over the sleep-wake cycle.”
    Quote in the paperNot a substantial claim
  • Premisecitation

    Circadian rhythms are observed in almost all physiologic measures, including endocrine and immune mediators.

    “Circadian rhythms are observed in almost all physiologic measures, including endocrine and immune mediators.15–17”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [15] Butler, 2009, Circadian regulation of endocrine functions

      Not checked in the free run.

    • cites [16] Cearley, 2003, Time of day differences in IL1beta and TNFalpha mRNA levels in specific regions of the rat brain, Neurosci Lett source

      Not checked in the free run.

    • cites [17] Lange, 2010, Effects of sleep and circadian rhythm on the human immune system, Ann N Y Acad Sci source

      Not checked in the free run.

  • May combine two claims. 42
  • Classified as probably not a substantial claim. 8

  • May combine two claims.

    Premisecitation

    Pro-inflammatory cytokines stimulate the production of cortisol, which then suppresses inflammatory cytokine production.

    “Pro-inflammatory cytokines stimulate the production of cortisol, which then suppresses inflammatory cytokine production.4,5”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [4] Munck, 1991, Glucocorticoids and immune function

      Not checked in the free run.

    • cites [5] Sapolsky, 2000

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  • May combine two claims.

    Premisecitation

    Sleep restriction causes substantial changes in the brain, with reversal after recovery sleep.

    “These subjective impressions are supported by numerous laboratory studies of endocrine function and metabolism as well as from investigations of sleep deprivation effects on cognitive and neural function, including research on the brain that shows a variety of substantial changes resulting from sleep restriction, with reversal after recovery sleep.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Sleep loss impacts mental health, metabolism, and immune function.

    “These subjective impressions are supported by countless studies exploring impacts of sleep (and sleep loss) on mental health, metabolism, and immune function.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Allostatic mediators work as a nonlinear, sometimes reciprocating, network, so too much or too little of each mediator can perturb the entire network, leading to harmful consequences.

    “Allostatic mediators work as a nonlinear, sometimes reciprocating, network (Fig. 1), meaning that too much or too little of each mediator can perturb the entire network, leading to harmful consequences.”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [1] Sterling, 1988, Allostasis: a new paradigm to explain arousal pathology

      Not checked in the free run.

    • cites [2] McEwen, 1993, Stress and the individual: mechanisms leading to disease, Arch Intern Med source

      Not checked in the free run.

    • cites [3] McEwen, 1998, Protective and damaging effects of stress mediators, N Engl J Med source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Increased sympathetic nervous system activity increases pro-inflammatory cytokine production, whereas parasympathetic activity decreases it.

    “Similarly, increased activity of the sympathetic nervous system increases pro-inflammatory cytokine production, whereas parasympathetic activity has the opposite effect.6,7”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [6] Borovikova, 2000, Vagus nerve stimulation attenuates the systemic inflammatory response to endotoxin, Nature source

      Not checked in the free run.

    • cites [7] Bierhaus, 2003, A mechanism converting psychosocial stress into mononuclear cell activation, Proc Natl Acad Sci U S A source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Peripheral clocks are synchronized to the SCN by a multitude of signals, including glucocorticoids, which can reset some peripheral clocks in the brain and body but not others.

    “These peripheral clocks are synchronized to the SCN by a multitude of signals, including glucocorticoids, which are able to “reset” some peripheral clocks in the brain and body (eg, liver), but not others.24”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [24] Balsalobre, 2000, Resetting of circadian time in peripheral tissues by glucocorticoid signaling, Science source

      Not checked in the free run.

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

    Premisecitation

    Allostatic overload includes conditions such as hypertension, atherosclerosis, diabetes, and metabolic syndrome, as well as stress-induced remodeling in brain regions that support memory, executive function, and anxiety.

    “Other examples of allostatic overload include conditions such as hypertension, atherosclerosis, diabetes, and the metabolic syndrome as well as stress-induced remodeling in brain regions that support memory, executive function, and anxiety.3,10”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [3] McEwen, 1998, Protective and damaging effects of stress mediators, N Engl J Med source

      Not checked in the free run.

    • cites [10] McEwen, 2004, Structural plasticity of the adult brain: how animal models help us understand brain changes in depression and systemic disorders related to depression, Dialogues Clin Neurosci source

      Not checked in the free run.

  • May combine two claims.

    Premisereasoning

    Metabolic symptoms are reported in both Cushing disease and major depression, associated with chronic elevation of cortisol that results in gradual loss of minerals from bone and increases in abdominal obesity.

    “Metabolic symptoms are also reported in both Cushing and major depression, as both are associated with chronic elevation of cortisol that results in gradual loss of minerals from bone, and increases in abdominal obesity.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    The master circadian clock is located in the SCN of the hypothalamus and drives all rhythms in physiology and behavior.

    “The master circadian clock is located in the SCN of the hypothalamus and drives all rhythms in physiology and behavior.21–23”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [21] Moore-Ede, 1986, Physiology of the circadian timing system: predictive versus reactive homeostasis, Am J Physiol

      Not checked in the free run.

    • cites [22] Moore, 1972, Loss of a circadian adrenal corticosterone rhythm following suprachiasmatic lesions in the rat, Brain Res source

      Not checked in the free run.

    • cites [23] Klein, 1991

      Not checked in the free run.

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

    Premisecitation

    Circadian disruption and sleep deprivation are not uncommon in the modern world and constitute an increasing health concern.

    “this is important because circadian disruption (CD; eg, shift work and jet lag) and sleep deprivation are not uncommon in the modern world and constitute an increasing health concern.19,20”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [19] Boivin, 2007, Working on atypical schedules, Sleep Med source

      Not checked in the free run.

    • cites [20] Knutsson, 2003, Health disorders of shift workers, Occup Med (Lond) source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Too much cortisol can suppress pro-inflammatory responses, compromising immune defenses.

    “However, at the opposite extreme, too much cortisol can suppress pro- inflammatory responses, thus compromising immune defenses.4,8”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [4] Munck, 1991, Glucocorticoids and immune function

      Not checked in the free run.

    • cites [8] Sapolsky, 2000, How do glucocorticoids influence stress responses? Integrating permissive, suppressive, stimulatory, and preparative actions, Endocr Rev

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S4 (based).

    Premisenone given

    The specific mechanisms by which disrupted circadian clocks cause changes in brain, behavior, and peripheral physiology remain unknown.

    “The specific mechanisms by which disrupted circadian clocks cause changes in brain, behavior, and peripheral physiology remain unknown.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisenone given

    Short-recovery individuals displayed a significant correlation between salivary cortisol levels and medial temporal cortex volume, whereas this effect was not observed in long recovery crews.

    “In addition to the neurobehavioral effects, short- recovery individuals displayed a significant correlation between salivary cortisol levels and medial temporal cortex volume, whereas this effect was not observed in long recovery crews.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationcitation

    Disrupted circadian patterns can result in unhealthy regulation of the HPA and thus could contribute to allostatic load.

    “It is posited that if efficient regulation of the HPA axis is a hallmark of a “healthy” response, then disrupted circadian patterns (or, in this case, a lack of a pattern) can result in an unhealthy regulation of the HPA and thus could contribute to allostatic load.27”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [27] Karatsoreos, 2011, Psychobiological allostasis: resistance, resilience and vulnerability, Trends Cogn Sci source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    eCD mice display an impulsive-like phenotype in the light-dark box, while not showing any overt anxiety-like phenotype.

    “In addition to the cognitive flexibility problems, eCD mice display what may be considered an “impulsive”-like phenotype in the light-dark box, while not showing any overt anxiety-like phenotype.34”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [34] Karatsoreos, 2011, Disruption of circadian clocks has ramifications for metabolism, brain, and behavior, Proc Natl Acad Sci U S A source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Mice that were circadian-disrupted but not explicitly sleep-deprived gained weight and had altered levels of plasma insulin and leptin.

    “This work is clearly supported by the earlier eCD work of Karatsoreos and McEwen,27 in which mice that were circadian-disrupted, but not explicitly sleep-deprived, gained weight and had altered levels of plasma insulin and leptin.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [27] Karatsoreos, 2011, Psychobiological allostasis: resistance, resilience and vulnerability, Trends Cogn Sci source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Short-duration sleep deprivation increases insulin levels and appetite, possibly through elevation of ghrelin and decreased levels of leptin.

    “Metabolic effects of this short-duration deprivation also include increased insulin levels and increased appetite, possibly through the elevation of ghrelin, a pro-appetitive hormone, and decreased levels of leptin.41–43”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [41] Leproult, 1997, Sleep loss results in an elevation of cortisol levels the next evening, Sleep

      Not checked in the free run.

    • cites [42] Spiegel, 1999, Impact of sleep debt on metabolic and endocrine function, Lancet source

      Not checked in the free run.

    • cites [43] Spiegel, 2004, Brief communication: sleep curtailment in healthy young men is associated with decreased leptin levels, elevated ghrelin levels, and increased hunger and appetite, Ann Intern Med source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    In adults, short-term sleep deprivation is not the cause of altered insulin sensitivity per se, but instead may contribute to overeating, potentially via different mechanisms in men and women.

    “Similarly, a study by St-Onge and colleagues46 in adults suggests that short-term sleep deprivation is not the cause of altered insulin sensitivity per se, but instead may contribute to overeating, potentially via different mechanisms in men and women.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [46] St-Onge, 2012, Short sleep duration, glucose dysregulation and hormonal regulation of appetite in men and women, Sleep source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    In adolescents, sleep reduction is associated with measurable changes in insulin sensitivity, whereas durations of sleep longer than average are not associated with such changes.

    “For instance, in adolescents, sleep reduction is associated with measurable changes in insulin sensitivity,45 whereas durations of sleep longer than average are not associated with such changes.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [45] Matthews, 2012, Sleep duration and insulin resistance in healthy black and white adolescents, Sleep source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Pro-inflammatory cytokine levels are increased following a modest sleep restriction to 6 hours per night, along with deterioration in performance as measured by tests of psychomotor vigilance.

    “Pro- inflammatory cytokine levels are increased, along with deterioration in performance as measured by tests of psychomotor vigilance, and this has been reported to result from a modest sleep restriction to 6 hours per night.48”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [48] Vgontzas, 2004, Adverse effects of modest sleep restriction on sleepiness, performance, and inflammatory cytokines, J Clin Endocrinol Metab source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Flight crews who endure more bouts of jet lag show shrunken medial temporal lobes, increased reaction time, and poorer performance in visual-spatial cognitive tasks compared with long recovery crews.

    “In humans, a study of flight crews showed that those who endure more bouts of jet lag (transmeridian, short recovery crews) show shrunken medial temporal lobes, increased reaction time, and poorer performance in visual-spatial cognitive tasks compared with long recovery crews.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisenone given

    Increases in blood pressure, decreases in parasympathetic tone, and increases in evening cortisol are observed after only 4 hours of sleep deprivation.

    “Increases in blood pressure, decreases in parasympathetic tone, and increases in evening cortisol are all observed after only 4 hours of sleep deprivation.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationreasoning

    Chronic stress compromises the ability of an organism to learn, remember, and make decisions, as well as increases levels of anxiety and aggression.

    “Thus, chronic stress compromises the ability of an organism to learn, remember, and make decisions, as well as increases levels of anxiety and aggression.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [58] McEwen, 2004, Molecular mechanisms of neuroplasticity and pharmacological implications: the example of tianeptine, Eur Neuropsychopharmacol source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Increases in brain levels of mRNA of the pro-inflammatory cytokine IL-1b are reported following sleep deprivation by gentle handling, and are higher in daytime than in darkness.

    “Specifically, increases in brain levels of mRNA of the pro-inflammatory cytokine IL-1b are reported following sleep deprivation by gentle handling and is reported to be higher in daytime (during the normal sleep period in rodents) than in darkness (during the normal activity time for rodents).59”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [59] Taishi, 1998, Sleep-associated changes in interleukin-1beta mRNA in the brain, J Interferon Cytokine Res source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Sleep restriction in animal models causes cognitive impairment and altered levels of cytokines, oxidative stress markers, glycogen, and reduced dentate gyrus neurogenesis.

    “For instance, there is recent evidence not only for cognitive impairment resulting from sleep restriction in animal models but also for altered levels of cytokines, oxidative stress markers, glycogen levels, and structural changes in the form of reduced dentate gyrus neurogenesis.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    Elevated evening cortisol as well as circadian disruption are linked to metabolic syndrome.

    “and elevated evening cortisol as well as CD are linked to metabolic syndrome.56”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [56] Rintamaki, 2008, Seasonal changes in mood and behavior are linked to metabolic syndrome, PLoS One source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    eCD can lead to significant changes in immune challenges while not dramatically altering basal inflammatory tone.

    “Indeed, recent work has demonstrated that eCD can lead to significant changes in immune challenges while not dramatically altering basal inflammatory tone.92,93”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [92]

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    • cites [93]

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  • May combine two claims.

    Premisecitation

    Chronic stress causes atrophy of neurons in the prefrontal cortex and hippocampus, and hypertrophy of neurons in the amygdala.

    “In animal models, chronic stress causes atrophy of neurons in the prefrontal cortex and hippocampus, brain regions involved in executive function, selective attention, and memory. On the other hand, chronic stress leads to hypertrophy of neurons in the amygdala, a region involved in fear, anxiety, and aggression.58”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [58] McEwen, 2004, Molecular mechanisms of neuroplasticity and pharmacological implications: the example of tianeptine, Eur Neuropsychopharmacol source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    The brain is the master regulator of the neuroendocrine, autonomic, and immune systems and of behaviors that contribute to healthy or unhealthy lifestyles.

    “The brain is the master regulator of the neuroendocrine, autonomic, and immune systems. It is important to remember that it is also the master regulator of behaviors that contribute to unhealthy or healthy lifestyles, which, in turn, influence the physiologic processes of allostasis.3”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [3] McEwen, 1998, Protective and damaging effects of stress mediators, N Engl J Med source

      Not checked in the free run.

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

    Premisecitation

    Glycogen in astrocytes is able to sustain axon function during glucose deprivation in central nervous system white matter.

    “although it is noteworthy that glycogen in astrocytes is able to sustain axon function during glucose deprivation in central nervous system white matter.65”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [65] Wender, 2000, Astrocytic glycogen influences axon function and survival during glucose deprivation in central white matter, J Neurosci source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Psychotic major depression involves elevated evening cortisol levels, whereas the nonpsychotic form does not.

    “Psychotic major depression involves elevated evening cortisol levels, whereas the nonpsychotic form does not,55”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [55] Keller, 2006, Cortisol circadian rhythm alterations in psychotic major depression, Biol Psychiatry source

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    Clear links exist between sleep deprivation, circadian disruption, and neurobehavioral, metabolic, and immune function.

    “Thus, clear links exist between sleep deprivation, CD, and neurobehavioral, metabolic, and immune function.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    Glycogen decreases by as much as 40% in rats deprived of sleep for 24 hours by novelty and gentle handling, an effect reversed by recovery sleep.

    “Glycogen, found predominantly in white matter, is also profoundly affected by sleep deprivation and is reported to decrease by as much as 40% in rats deprived of sleep for 24 hours by novelty and gentle handling, an effect reversed by recovery sleep.63,64”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [63] Kong, 2002, Brain glycogen decreases with increased periods to wakefulness: implications for homeostatic drive to sleep, J Neurosci source

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    • cites [64] Brown, 2004, Brain glycogen re-awakened, J Neurochem source

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  • May combine two claims.

    Premisecitation

    Glucocorticoids are able to reset and synchronize the circadian clocks of peripheral tissues, including the liver, although the central pacemaker clock of the SCN does not respond to glucocorticoid.

    “Moreover, glucocorticoids are able to reset and synchronize the circadian clocks of peripheral tissues, including the liver, although the central pacemaker clock of the SCN does not respond to glucocorticoid.24”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [24] Balsalobre, 2000, Resetting of circadian time in peripheral tissues by glucocorticoid signaling, Science source

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    The effects of sleep deprivation on behavior are not simple and are influenced by their type, intensity, duration, and the types of behavioral outcomes measured.

    “Thus, the effects of sleep deprivation are not simple and are influenced by their type, intensity, duration, and the types of behavioral outcomes measured.”
    Quote in the paperNot a substantial claim

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

    Premisecitation

    Epigenetic modifications might play a critical role in synaptic plasticity following sleep deprivation.

    “while new work also suggests that epigenetic modifications might play a critical role in synaptic plasticity following sleep deprivation.97”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [97]

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    Circadian disruption predisposes an individual to altered responses to stressors as well as impaired cognitive function and metabolic dysregulation.

    “Taken together, these changes in brain and body are further evidence that circadian disruption predisposes an individual to altered responses to stressors as well as impaired cognitive function and metabolic dysregulation.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    Long-distance air travel with short turnaround is associated with smaller volume of the temporal lobe and impaired performance on a visual-spatial cognitive task.

    “long distance air travel with short turnaround has been reported to be associated with smaller volume of the temporal lobe and impaired performance on a visual-spatial cognitive task.86”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [86] Cho, 2001, Chronic 'jet lag' produces temporal lobe atrophy and spatial cognitive deficits, Nat Neurosci source

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    Reduced sleep and circadian disruption are associated with increased chances of cardiovascular disease and diabetes.

    “As noted above, reduced sleep and CD are associated with increased chances of cardiovascular disease and diabetes.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationreasoning

    Sleep deprivation can be described as a chronic stressor that can cause allostatic overload, including mood and cognitive impairment and autonomic and metabolic dysregulation.

    “Sleep deprivation can be described as a chronic stressor that can cause allostatic overload, including mood and cognitive impairment and autonomic and metabolic dysregulation.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationnone given

    The long-term consequences of sleep deprivation and circadian disruption constitute a form of allostatic load, with consequences involving hypertension, reduced parasympathetic tone, increased pro-inflammatory cytokines, increased oxidative stress, and increased evening cortisol and insulin.

    “The long-term consequences of sleep deprivation and CD constitute a form of allostatic load, with consequences involving hypertension, reduced parasympathetic tone, increased pro-inflammatory cytokines, increased oxidative stress, and increased evening cortisol and insulin.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationreasoning

    There are linkages between the multiple interacting mediators involved in allostasis and allostatic load/overload, and overlaps (comorbidities) between disorders such as diabetes, hypertension, cardiovascular disease, and depression that are associated with excessive stress and dysregulation of systems that normally promote allostasis and successful adaptation.

    “Thus, there are not only linkages between the multiple, interacting mediators that are involved in allostasis and allostatic load/overload, as summarized in Fig. 1, but also overlaps (ie, comorbidities) between disorders, such as diabetes, hypertension, cardiovascular disease, and depression, that are associated with excessive stress and with the dysregulation of the systems that normally promote”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based). May combine two claims.

    Interpretationnone given

    Circadian disruption is a broader aspect of the problem of sleep disruption, with disruption of the circadian clock contributing to changes in sleep patterns, and sleep patterns potentially influencing the circadian clock.

    “CD is a broader aspect of the problem of sleep disruption, with disruption of the circadian clock contributing to changes in sleep patterns, and sleep patterns potentially influencing the circadian clock.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Shift work and jet lag are common practices that have measurable effects on the brain and body.

    “Shift work and jet lag are 2 common practices that have measurable effects on the brain and body.84,85”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [84] Atkinson, 2007, Relationships between sleep, physical activity and human health, Physiol Behav source

      Not checked in the free run.

    • cites [85] Karlson, 2006, Diurnal cortisol pattern of shift workers on workday and a day off, Scand J Work Environ Health

      Not checked in the free run.

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

    Premisecitation

    Sleep is thought to be a neural state during which consolidation of declarative memories takes place.

    “Sleep is thought to be a neural state during which consolidation of declarative memories takes place.83”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [83] Gais, 2004, Declarative memory consolidation: mechanisms acting during human sleep, Learn Mem source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S4 (based). May combine two claims.

    Interpretationnone given

    Sleep deprivation, even for the course of the active period of the day in diurnal animals, increases the homeostatic drive to sleep, with resulting changes in pro-inflammatory cytokines and glycogen levels.

    “Sleep deprivation, even for the course of the active period of the day in diurnal animals, increases the homeostatic drive to sleep, with resulting changes in pro-inflammatory cytokines and glycogen levels.”
    Quote in the paperNot a substantial claim
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Each is checked against this paper’s own text: does it say what the citing paper says it does?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

Each contradiction between two passages listed here was confirmed by an independent check.

  • Cortisol sample type changes for the flight-crew correlation

    Minor

    The flight-crew finding is described first as a correlation with salivary cortisol, then summarized in the same paragraph as a correlation with plasma cortisol. The text does not report a separate plasma measurement for that finding.

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Cites

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Authors
McEwen, B. S., & Karatsoreos, I. N.
Affiliations
  • Rockefeller University (US)
  • Washington State University (US)
Corresponding author
McEwen, Bruce S.
ORCID
Venue
Sleep Medicine Clinics
Publisher
Elsevier BV
Published
2015-03
Volume
10
Issue
1
Pages
1-10
ISSN
1556-407X (ISSN-L)
DOI
10.1016/j.jsmc.2014.11.007
PMC
PMC8935364
OpenAlex
W2122955643
Semantic Scholar
f0988dd90e7f0fe923e76dabc222492f190913cc
Cited by
338
References
105
Citations by year
2026: 27 · 2025: 49 · 2024: 31 · 2023: 27 · 2022: 31 · 2021: 46 · 2020: 24 · 2019: 25 · 2018: 32 · 2017: 21 · 2016: 17 · 2015: 7 · 2014: 1
FWCI
3.13
Type
journal article
Language
en
Open access
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations
  • Sleep Medicine Clinics (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Institute of Mental Health (R01MH041256)
  • National Institute of Diabetes and Digestive and Kidney Diseases (R01DK119811)
Topics
  • Social Sciences › Psychology › Experimental and Cognitive Psychology › Sleep and Work-Related Fatigue
  • Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Sleep and Wakefulness Research
Keywords
sleep deprivation, circadian rhythm disruption, circadian rhythm, sleep homeostasis, stress, anxiety, depression, shift work, jet lag, brain function, cumulative stress
MeSH terms
Animals, Circadian Rhythm, Humans, Sleep Deprivation, Stress, Psychological, Mood Disorders, Allostasis

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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