Severe Sleep Loss Research Articles

Perinatal sleep disruption and postpartum psychosis in bipolar disorder: Findings from the UK BDRN Pregnancy Study

BackgroundWomen with bipolar disorder (BD) are at high risk of postpartum psychosis (PP). The factors that increase risk of PP among women with BD are not fully understood. Here, we examine whether sleep disruption in the perinatal period (poor sleep quality in late pregnancy and sleep deprivation related to childbirth) is associated with PP in a longitudinal study of pregnant women with BD. MethodsParticipants were 76 pregnant women with lifetime DSM-5 bipolar I disorder or schizoaffective-BD, followed from week 12 of pregnancy to 12 weeks postpartum. Demographics and lifetime psychopathology were assessed at baseline via semi-structured interview (Schedules for Clinical Assessment in Neuropsychiatry). Psychopathology and sleep disruption within the current perinatal period were assessed in the third trimester and at 12 weeks postpartum. Data were supplemented by clinician questionnaires and case-note review. ResultsAfter controlling for prophylactic use of mood stabilising medication, the loss of at least one complete night of sleep across labour/delivery was associated with five times the odds of experiencing PP compared to no or less than one night of sleep loss across labour/delivery (OR 5.19, 95 % CI 1.45–18.54; p = 0.011). Sleep quality in late pregnancy was not associated with PP, and perinatal sleep disruption was not associated with postpartum depression. LimitationsLack of objective measures of sleep factors. ConclusionsIn the context of other aetiological factors, severe sleep loss associated with childbirth/the immediate postpartum may act as a final trigger of PP. These findings could have important clinical implications for risk prediction and prevention of PP.

0161 Structural Changes in Mood Domains During Sleep Deprivation and Recovery

Abstract Introduction Mood is known to vary as a function of sleep debt. Mood batteries often measure multiple, non-orthogonal domains. In the present study, the latent structure of the Automated Neuropsychological Assessment Metrics Mood (ANAM-mood) battery was assessed during five different states of alertness. We present a novel scheme to evaluate changes in the structure of such batteries across conditions. It was hypothesized that the structure would change, with the greatest changes manifest during sleep deprivation. Methods The present analyses were conducted on data from a prior sleep deprivation study (n = 25 healthy young adults). We used the identity property of MANOVA. Given correlation matrices Σi and Σj, structural invariance was defined as Σi Σj-1 ≈ I (Identity). MANOVA statistic m was the largest eigenvalue of Σi Σj-1. Resampling was used to generate m-distributions within and between the five different alertness conditions - Rested, Sleep Deprived (SD) days 1 and 2, and Recovery days 1 and 2. In addition, the relative number of mood dimensions was estimated by the odds (via resampling) of two dimensions explaining 80% of the variance of Σi compared to Σj. Results The pairwise MANOVA-statistic revealed significant structural variations across conditions (p< 0.001 for all comparisons). Significant differences included Rested vs SD1 and SD2. Recovery 1 showed the most pronounced differences to all conditions. Recovery 2 was like Recovery 1, but more like Rested than the prior day. The odds ratio of two-dimensions for Recovery 1 was much higher compared to all other conditions (OR: 2.4-245, p< 0.001). Conclusion Individuals respond differently to a mood survey across specific alertness conditions resulting in structural changes to the data. Wakefulness during recovery from severe sleep loss differs most significantly from all states, contrary to our hypothesis. This is important to consider when interpreting mood changes as measured by such batteries (including related Spielberger's State Anxiety Inventory and Beck Depression Inventory-II) during sleep studies. Follow up studies are needed to fully assess such effects and devise methods to account for them. Support (if any) This effort was fully supported by the Department of Defense Military Operational Medicine Research Program (MOMRP).

Digital Addiction and Sleep.

In 2020, the World Health Organization formally recognized addiction to digital technology (connected devices) as a worldwide problem, where excessive online activity and internet use lead to inability to manage time, energy, and attention during daytime and produce disturbed sleep patterns or insomnia during nighttime. Recent studies have shown that the problem has increased in magnitude worldwide during the COVID-19 pandemic. The extent to which dysfunctional sleep is a consequence of altered motivation, memory function, mood, diet, and other lifestyle variables or results from excess of blue-light exposure when looking at digital device screens for long hours at day and night is one of many still unresolved questions. This article offers a narrative overview of some of the most recent literature on this topic. The analysis provided offers a conceptual basis for understanding digital addiction as one of the major reasons why people, and adolescents in particular, sleep less and less well in the digital age. It discusses definitions as well as mechanistic model accounts in context. Digital addiction is identified as functionally equivalent to all addictions, characterized by the compulsive, habitual, and uncontrolled use of digital devices and an excessively repeated engagement in a particular online behavior. Once the urge to be online has become uncontrollable, it is always accompanied by severe sleep loss, emotional distress, depression, and memory dysfunction. In extreme cases, it may lead to suicide. The syndrome has been linked to the known chronic effects of all drugs, producing disturbances in cellular and molecular mechanisms of the GABAergic and glutamatergic neurotransmitter systems. Dopamine and serotonin synaptic plasticity, essential for impulse control, memory, and sleep function, are measurably altered. The full spectrum of behavioral symptoms in digital addicts include eating disorders and withdrawal from outdoor and social life. Evidence pointing towards dysfunctional melatonin and vitamin D metabolism in digital addicts should be taken into account for carving out perspectives for treatment. The conclusions offer a holistic account for digital addiction, where sleep deficit is one of the key factors.

Geographical variations in the association between bullying victimization and sleep loss among adolescents: a population-based study of 91 countries

ObjectiveTo examine geographical variations in the association between bullying victimization and sleep loss over worry among adolescents. MethodsWe used data from the Global School-based Student Health Survey conducted between 2003 and 2017 in 91 countries across the globe. Sleep loss was categorised as: none/minimum (reported never or rarely sleep loss), moderate (reported sometimes), and severe (reported most of the time or always). We obtained country-specific estimates from multiple multinomial logistic regression analyses and pooled estimates from meta-analyses. ResultsOf 282,036 adolescents 13–17 years of age, 28.1% (male: 25.4%, female: 31.0%) and 8.4% (male: 7.3%, female: 9.5%) of adolescents reported moderate and severe sleep loss respectively. Adolescents who frequently experienced bullying (≥3 per 30 days) reported higher prevalence of severe sleep loss. Meta-analyses showed that increased frequency of bullying victimization is associated with increased odds of sleep loss, with adolescents who experienced bullying for ≥3 days in the past 30 days were 1.65 and 2.65 times more likely than adolescents without being bullied to experience respectively moderate (OR 1.65, 95% CI: 1.59–1.72) and severe (OR 2.65, 95% CI: 2.52–2.79) sleep loss. Irrespective of sex, the association between bullying victimization and sleep loss was significant in all regions, income groups, and in all but a few countries. ConclusionsIncreased frequency of bullying victimization is positively associated with increased sleep loss among adolescents. Appropriate policies and programmes to stop bullying at school could help downgrade the risk of sleep loss among adolescents.

Sleep Loss Can Cause Death through Accumulation of Reactive Oxygen Species in the Gut

The view that sleep is essential for survival is supported by the ubiquity of this behavior, the apparent existence of sleep-like states in the earliest animals, and the fact that severe sleep loss can be lethal. The cause of this lethality is unknown. Here we show, using flies and mice, that sleep deprivation leads to accumulation of reactive oxygen species (ROS) and consequent oxidative stress, specifically in the gut. ROS are not just correlates of sleep deprivation but drivers of death: their neutralization prevents oxidative stress and allows flies to have a normal lifespan with little to no sleep. The rescue can be achieved with oral antioxidant compounds or with gut-targeted transgenic expression of antioxidant enzymes. We conclude that death upon severe sleep restriction can be caused by oxidative stress, that the gut is central in this process, and that survival without sleep is possible when ROS accumulation is prevented. VIDEO ABSTRACT.

Sleep Loss Promotes Astrocytic Phagocytosis and Microglial Activation in Mouse Cerebral Cortex.

We previously found that Mertk and its ligand Gas6, astrocytic genes involved in phagocytosis, are upregulated after acute sleep deprivation. These results suggested that astrocytes may engage in phagocytic activity during extended wake, but direct evidence was lacking. Studies in humans and rodents also found that sleep loss increases peripheral markers of inflammation, but whether these changes are associated with neuroinflammation and/or activation of microglia, the brain's resident innate immune cells, was unknown. Here we used serial block-face scanning electron microscopy to obtain 3D volume measurements of synapses and surrounding astrocytic processes in mouse frontal cortex after 6-8 h of sleep, spontaneous wake, or sleep deprivation (SD) and after chronic (∼5 d) sleep restriction (CSR). Astrocytic phagocytosis, mainly of presynaptic components of large synapses, increased after both acute and chronic sleep loss relative to sleep and wake. MERTK expression and lipid peroxidation in synaptoneurosomes also increased to a similar extent after short and long sleep loss, suggesting that astrocytic phagocytosis may represent the brain's response to the increase in synaptic activity associated with prolonged wake, clearing worn components of heavily used synapses. Using confocal microscopy, we then found that CSR but not SD mice show morphological signs of microglial activation and enhanced microglial phagocytosis of synaptic elements, without obvious signs of neuroinflammation in the CSF. Because low-level sustained microglia activation can lead to abnormal responses to a secondary insult, these results suggest that chronic sleep loss, through microglia priming, may predispose the brain to further damage.SIGNIFICANCE STATEMENT We find that astrocytic phagocytosis of synaptic elements, mostly of presynaptic origin and in large synapses, is upregulated already after a few hours of sleep deprivation and shows a further significant increase after prolonged and severe sleep loss, suggesting that it may promote the housekeeping of heavily used and strong synapses in response to the increased neuronal activity of extended wake. By contrast, chronic sleep restriction but not acute sleep loss activates microglia, promotes their phagocytic activity, and does so in the absence of overt signs of neuroinflammation, suggesting that like many other stressors, extended sleep disruption may lead to a state of sustained microglia activation, perhaps increasing the brain's susceptibility to other forms of damage.

Short-term moderate sleep restriction decreases insulin sensitivity in young healthy adults

Context and purposeThe literature suggests that severe sleep loss of more than a few hours a night decreases glucose tolerance and insulin sensitivity. The aim of this study was to determine whether moderate sleep restriction had similar effects. MethodsFifteen healthy non-obese (body mass index = 24.5 ± 3.4 kg/m2) young adults (20.6 ± 1.3 years) completed two 2-hour oral glucose tolerance tests (OGTTs): one was after 3 days of time-in-bed restriction by 1 to 3 hours each night, and the other was after 3 days of ad libitum sleep. Glucose and insulin concentrations during OGTT and fasting glucagon and cortisol concentrations were determined. The homeostasis model of insulin resistance, Matsuda index, and the quantitative insulin sensitivity check index were calculated. ResultsThe total time-in-bed during the sleep restriction and the ad libitum phase was 5.98 ± 0.76 and 7.98 ± 0.54 hours/day, and total sleep time was 5.16 ± 0.49 and 6.65 ± 0.64 hours/day, respectively. Glucose concentrations before and 30, 60, 90, and 120 minutes after consumption of glucose and area under the curve were not different for the 2 OGTTs (P > .10 for all). Insulin concentration at fasting and area under the curve during the OGTT were significantly higher (P = .034 and .038, respectively) after restricted sleep than after ad libitum sleep. Fasting glucagon concentration was also higher (P = .003). The homeostasis model of insulin resistance, Matsuda index, and quantitative insulin sensitivity check index all suggested decreased insulin sensitivity after restricted sleep. ConclusionShort-term moderate sleep restriction reduced insulin sensitivity compared to ad libitum sleep in this group of healthy young adults.

Short‐term Moderate Sleep Restriction Increases Insulin Concentration Following Oral Glucose Tolerance Test

The literature suggests that severe sleep loss of more than a few hours a night decreases glucose tolerance and insulin sensitivity. This study was to determine whether moderate sleep restriction had similar effects. Methods Fifteen healthy non-obese (BMI=24.5±3.4 kg/m2) young adults (20.6±1.3 years) completed two oral glucose tolerance tests: one was after 3 days of restricted sleep by two hours each day, and the other was after 3 days of ad libitum sleep. Plasma samples were collected before and 30, 60, 90, and 120 minutes after consumption of a glucose drink to determine glucose and insulin concentrations. Fasting C-peptide concentration was also determined. Results Glucose concentrations before and 30, 60, 90, and 120 minutes following consumption of glucose were not different during the two glucose tolerance tests (p > 0.10 for all). Glucose area under the curve was also similar (p > 0.10). Insulin concentrations before and 60, 90, and 120 minutes following consumption of glucose were not different (p > 0.10 for all), but insulin concentration 30 minutes following consumption of glucose was higher (p = 0.038) after restricted sleep (31.4±19.8 uIU/ml) than ad libitum sleep (23.7±17.4 uIU/ml). Insulin area under the curve and fasting C-peptide concentration were also greater (p = 0.056 and p = 0.059, respectively) following restricted sleep than ad libitum sleep. Conclusion Short-term moderate sleep restriction of only two hours may have adverse effects on glucose metabolism by increasing insulin concentration in this group of healthy young adults.

Sleep restriction and degraded reaction-time performance in Figaro solo sailing races

In solo offshore sailing races like those of the Solitaire du Figaro, sleep must be obtained in multiple short bouts to maintain competitive performance and safety. Little is known about the amount of sleep restriction experienced at sea and the effects that fatigue from sleep loss have on sailors’ performance. Therefore, we assessed sleep in sailors of yachts in the Figaro 2 Beneteau class during races and compared response times on a serial simple reaction-time test before and after races. Twelve men (professional sailors) recorded their sleep and measured their response times during one of the three single-handed races of 150, 300 and 350 nautical miles (nominally 24–50 h in duration). Total estimated sleep duration at sea indicated considerable sleep insufficiency. Response times were slower after races than before. The results suggest that professional sailors incur severe sleep loss and demonstrate marked performance impairment when competing in one- to two-day solo sailing races. Competitive performance could be improved by actively managing sleep during solo offshore sailing races.

Ablation of Kv3.1 and Kv3.3 Potassium Channels Disrupts Thalamocortical OscillationsIn VitroandIn Vivo

The genes Kcnc1 and Kcnc3 encode the subunits for the fast-activating/fast-deactivating, voltage-gated potassium channels Kv3.1 and Kv3.3, which are expressed in several brain regions known to be involved in the regulation of the sleep-wake cycle. When these genes are genetically eliminated, Kv3.1/Kv3.3-deficient mice display severe sleep loss as a result of unstable slow-wave sleep. Within the thalamocortical circuitry, Kv3.1 and Kv3.3 subunits are highly expressed in the thalamic reticular nucleus (TRN), which is thought to act as a pacemaker at sleep onset and to be involved in slow oscillatory activity (spindle waves) during slow-wave sleep. We showed that in cortical electroencephalographic recordings of freely moving Kv3.1/Kv3.3-deficient mice, spectral power is reduced up to 70% at frequencies <15 Hz. In addition, the number of sleep spindles in vivo as well as rhythmic rebound firing of TRN neurons in vitro is diminished in mutant mice. Kv3.1/Kv3.3-deficient TRN neurons studied in vitro show approximately 60% increase in action potential duration and a reduction in high-frequency firing after depolarizing current injections and during rebound burst firing. The results support the hypothesis that altered electrophysiological properties of TRN neurons contribute to the reduced EEG power at slow frequencies in the thalamocortical network of Kv3-deficient mice.

The sensitivity of a palm-based psychomotor vigilance task to severe sleep loss

In this study, we evaluated the sensitivity of a 5-min personal digital assistant-psychomotor vigilance test (PDA-PVT) to severe sleep loss. Twenty-one participants completed a 10-min PVT-192 and a 5-min PDA-PVT at two hourly intervals during 62 h of sustained wakefulness. For both tasks, response speed and number of lapses (RTs > 500) per minute significantly increased with increasing hours of wakefulness. Overall, standardized response speed scores on the 5-min PDA-PVT closely tracked those of the PVT-192; however, the PDA-PVT was generally associated with more lapses/minute. Closer inspection of the data indicated that when the level of sleep loss and fatigue became more severe (i.e., Day 3), the 5-min PDA-PVT was not quite as sensitive as the 10-min PVT-192 when 2- to 10-sec foreperiods were used for both. It is likely, however, that the observed differences between the two devices was due to differences in task length. Thus, the findings provide further evidence of the validity of the 5-min PDA-PVT as a substitute for the 10-min PVT-192, particularly in circumstances in which a shorter test is required and/or the PVT-192 is not as practical.

Sleep deprivation in the pigeon using the Disk-Over-Water method

A well-defined sleep deprivation (SD) syndrome has been observed in studies with rats under conditions of severe sleep loss on the Disk-Over-Water (DOW) apparatus. Observation of the sleep deprivation syndrome across taxa would assist in the elucidation of the function of sleep. In the present study, the effects of total sleep deprivation were assessed in pigeons, a biologically relevant choice given that birds are the only non-mammalian taxon known to exhibit unequivocal rapid-eye-movement (REM) sleep and non-REM (NREM) sleep. Pigeons were deprived of sleep for 24–29 days on the DOW by rotating the disk and requiring them to walk whenever sleep was initiated. Control (C) birds were also housed on the DOW and required to walk only when the deprived (D) birds were required to walk due to sleep initiation. NREM and REM sleep amounts were reduced from baseline during the deprivation for both D and C birds, although D birds obtained less NREM sleep than controls. Across the deprivation, D birds had their total sleep reduced by 54% of baseline (scored in 4 s epochs), whereas previous studies in rats on the DOW reported total sleep reduction of as much as 91% (scored in 30 s epochs). Pigeons proved to be more resistant to sleep deprivation by the DOW method and were much more difficult to deprive over the course of the experiment. Overall, the pigeons showed recovery sleep patterns similar to those seen in rats; i.e., rebound sleep during recovery was disproportionately composed of REM sleep. They did not, however, show the obvious external physical signs of the SD syndrome nor the large metabolic and thermoregulatory changes associated with the syndrome. The DOW method was thus effective in producing sleep loss in the pigeon, but was not as effective as it is in rats. The absence of the full SD syndrome is discussed in the context of limitations of the DOW apparatus and the possibility of species-specific adaptations that birds may possess to withstand or adapt to conditions of limited sleep opportunity.

Sleep duration and quality in healthy nulliparous and multiparous women across pregnancy and post‐partum

Longitudinal studies of sleep during normal pregnancy and post-partum are rare, and interpretation of the findings is often hampered by methodological issues. Consequentially, there is still limited information on what constitutes normal sleep quality and quantity across pregnancy and early post-partum, for both nulliparous and multiparous women. To quantify the change and variability in sleep duration and quality across pregnancy and post-partum for healthy nulliparous and multiparous women. Nineteen women (eight nulliparous and 11 multiparous) wore an actigraph and completed a sleep diary to objectively measure sleep for seven nights during the second trimester, one week prior to delivery, and at one and six weeks post-partum. Mixed model analysis of variance and logistic regression were used to investigate changes in sleep across this timeframe. The largest changes in sleep occurred in the first week post-partum (1.5 h less sleep than during pregnancy, three times more sleep episodes in 24 h, 70% of women regularly napping during the day, and greatest day-to-day variability in sleep). Compared to multiparas, nulliparas generally had less efficient sleep, spent more time in bed and had greater wake after sleep onset in the second trimester, and spent less time in bed and had fewer sleep episodes a day at one week post-partum. These changes should be used to inform women about the extent of change in sleep, particularly early post-partum, and to help health-care providers identify women experiencing severe sleep loss and disruption and discuss possible coping strategies with them.

Time estimation during prolonged sleep deprivation and its relation to activation measures.

This is the first study to analyze variations in time estimation during 60 h of sleep deprivation and the relation between time estimation performance and the activation measures of skin resistance level, body temperature, and Stanford Sleepiness Scale (SSS) scores. Among 30 healthy participants 18 to 24 years of age, for a 10-s interval using the production method, we found a lengthening in time estimations that was modulated by circadian oscillations. No differences in gender were found in the time estimation task during sleep deprivation. The variations in time estimation correlated significantly with body temperature, skin resistance level, and SSS throughout the sleep deprivation period. When body temperature is elevated, indicating a high level of activation, the interval tends to be underestimated, and vice versa. When the skin resistance level or SSS is elevated (low activation), time estimation is lengthened, and vice versa. This lengthening is important because many everyday situations involve duration estimation under moderate to severe sleep loss. Actual or potential applications of this research include transportation systems, emergency response work, sporting activities, and industrial settings in which accuracy in anticipation or coincidence timing is important for safety or efficiency.

Stimulant Drug Effects on Performance and Behavior After Prolonged Sleep Deprivation: A Comparison of Amphetamine, Nicotine, and Deprenyl

Normal male subjects (N = 102) underwent total sleep deprivation in a laboratory environment for 48 hr. In separate dose-response, double-blind, placebo-controlled experiments, 36 subjects received single doses of d- amphetamine, 35 received intravenous nicotine, and 31 received l-deprenyl. All were deprived of sleep for an additional 12 hr. Amphetamine reversed the effects of sleep loss in a dose-related way, but the pattern and persistence of the reversal varied across measures. Neither nicotine nor I-deprenyl produced substantial persistent reversal of sleep deprivation effects. We conclude that these latter two agents are unlikely to be useful for the acute remediation of the effects of severe sleep loss. Although amphetamine is acutely effective, its usefulness in the treatment or prophylaxis of sleep loss requires further study.