Can People Sleep Too Much? Effects of Extended Sleep Opportunity on Sleep Duration and Timing

Many people are concerned about whether they are getting “enough” sleep, and if they can “sleep too much.” These concerns can be approached scientifically using experiments probing long-term (i.e., multi-night) sleep homeostatic processes, since homeostatic processes move the system toward its physiological setpoint (i.e., between “not enough” and “too much”). We analyzed sleep data from two human studies with sleep opportunities much longer than people usually stay in bed (i.e., conditions in which sleep homeostatic responses could be documented): sleep opportunities were 14–16 h per day for 3–28 days. Across the nights of the extended sleep opportunities, total sleep duration, Rapid Eye Movement (REM) sleep duration and non-REM sleep durations decreased and sleep latency increased. Multiple nights were required to reach approximately steady-state values. These results suggest a multi-day homeostatic sleep process responding to self-selected insufficient sleep duration prior to the study. Once steady state-values were reached, there were large night-to-night variations in total sleep time and other sleep metrics. Our results therefore answer these concerns about sleep amount and are important for understanding the basic physiology of sleep and for two sleep-related topics: (i) the inter-individual and intra-individual variability are relevant to understanding “normal” sleep patterns and for people with insomnia and (ii) the multiple nights of sleep required for recovery from insufficient sleep from self-selected sleep loss is important for public health and other efforts for reducing the adverse effects of sleep loss on multiple areas of physiology.

Tonic endocannabinoid signaling supports sleep through development in both sexes.

Sleep is an essential behavior that supports brain function and cognition throughout life, in part by acting on neuronal synapses. The synaptic signaling pathways that mediate the restorative benefits of sleep are not fully understood, particularly in the context of development. Endocannabinoids (eCBs) including 2-arachidonyl glycerol (2-AG) and anandamide (AEA), are bioactive lipids that activate cannabinoid receptor, CB1, to regulate synaptic transmission and mediate cognitive functions and many behaviors, including sleep. We used targeted mass spectrometry to measure changes in forebrain synaptic eCBs during the sleep/wake cycle in developing and adult mice. We find that eCBs are downregulated in response to acute sleep deprivation in juvenile mice, while in young adults eCBs are upregulated during the sleep phase in a circadian manner. Next we manipulated the eCB system using selective pharmacology and measured the effects on sleep behavior in developing and adult mice of both sexes using a non-invasive piezoelectric home-cage recording apparatus. Enhancement of eCB signaling through inhibition of 2-AG or AEA degradation, increased dark phase sleep amount and bout length in developing and adult males, but not in females. Inhibition of CB1 by injection of the antagonist AM251 reduced sleep time and caused sleep fragmentation in developing and adult males and females. Our data suggest that males are more sensitive to the sleep promoting effects of enhanced eCBs but that tonic eCB signaling supports sleep behavior through multiple stages of development in both sexes. This work informs the further development of cannabinoid-based therapeutics for sleep disruption.

219 Comparing Sleep Amount and Quality for People Working from Home with and Without Minor Dependents during the COVID-19 Pandemic

Introduction The global pandemic due to the novel coronavirus (COVID-19) has had unprecedented effects on society, in particular for those who are also working with children in the household. The aim of this analysis was to evaluate sleep amount and sleep quality during the COVID-19 pandemic compared to before COVID-19 for those working from home with minor household dependents. Methods We developed the “Anonymous Survey on Confinement during the COVID-19 Pandemic”, a national survey for individuals ≥18 years of age hosted on the Penn Medicine Clinical Research website from May 16th to November 11th, 2020. This 200 question survey captured demographics and multiple dimensions of health and well-being, including stress, sleep, eating behaviors, and coping activities. Respondents who indicated they were working from home were stratified by whether they were living with ≥1 minor dependent vs no dependents. Separate ordinal logistic regression models were used to evaluate associations between living with a minor dependent and sleep amount (less, same, more) and disturbed quality (none, less, same, more) during, compared to before, COVID-19 controlled for age, sex, ethnicity, and annual income. Results A total of 232 respondents (n=182 no dependents, n=50 dependents, 84.9% Caucasian) reported working from home, the majority of which had been in confinement (95.7%). Respondents with dependents were younger (mean age 38.9±13.5 vs 47.4±18.0, p=0.002) and mostly female (86% vs 76.9%, p=0.03). On average, reported days worked/week (3.5±2.4 days) and hours worked/day (5.5±4.17 hours) were similar regardless of dependents. Comparing those without to those with minor dependents, there were no significant differences in log odds of getting enough sleep (β=-0.38, p=0.25) or worse sleep quality (β=0.41, p=0.22) during the COVID-19 pandemic compared to before COVID-19. Respondents with dependents reported a higher log odds of taking longer to fall asleep during COVID-19 (β=0.71, p=0.045), and higher stress (β=-0.65, p=0.04). Conclusion In this mostly Caucasian female sample of people working from home, having minor dependents in the household did not significantly impact sleep amount or quality compared to no minor household dependents. However, respondents with dependents reported longer time to fall asleep and were more stressed. Support (if any) MC/CJ are supported by NHLBI (T32 HL007713).

226 Changes in sleep amount and sleep quality due to the COVID-19 pandemic confinement associate with ratings of health and stress

Introduction In March 2020, an unprecedented number of individuals were confined to their homes in an effort to stem the spread of the novel Coronavirus (Covid-19), however the impact of this confinement on health and behavior is unknown. Long-duration confinement studies have found effects on homeostatic biology and neurobehavioral functions, including reduced sleep durations. This study evaluated how confinement due to Covid-19 has impacted health and stress through changes in sleep. Methods The Anonymous Survey on Confinement during the COVID-19 Pandemic was available online to any individual ≥18 years of age through the Penn Medicine Clinical Research webpage on May 14, 2020 and the data presented are through October 24, 2020. The survey collected self-reported information on demographics, the amount and quality of sleep, as well as ratings of health and stress. To determine the impact of confinement on these domains, participants were asked to answer questions relative to pre-confinement levels. To test associations between sleep amounts and sleep quality on health and stress, generalized linear models were used and adjusted for age, sex, and race. Results N=228 participants (n=180 female [79.0%]) were on average 45.0±17.1 years of age. During confinement relative to pre-confinement, 41.7% of participants reported sleeping more, 37.3% reported sleeping the same amount, and 21.0% reported less sleep, while 14.0% reported better sleep quality, 47.4% the same, and 38.6% worse quality of sleep relative to pre-confinement. Ratings of worse health during confinement were associated with both reduced sleep amount (β=0.695; P<0.0001) and worse sleep quality (β=0.532; P=0.0002). Lower stress ratings were associated with increased sleep amount (β=0.734; P=0.034), better sleep quality (β=1.396; P=0.0002), better health ratings (β=-0.079; P=0.0045). Conversely, worse sleep quality was associated with higher stress ratings (β=-1.086; P=0.0007). Conclusion The confinement resulting from the COVID-19 pandemic has impacted the amount and quality of sleep and good sleep may help to reduce stress and maintain health. These findings highlight the need to further examine how long-term confinement influences human health and behavior and warrant examining what factors or life-style behaviors promote resilience to the negative effects of confinement. Support (if any) CWJ supported by NHLBI NRSA (T32 HL007713).

215 Sleep duration, quality and timing during confinement amid the COVID-19 Pandemic

Introduction As of March 2020, most U.S. states and territories issued statements advising people “stay at home” to avoid spreading the novel Coronavirus (COVID-19). This resulted in an unprecedented number of people practicing physical confinement and social distancing. This study examined self-reported changes in sleep duration, quality and timing in response to confinement and isolation. Methods We developed the “Anonymous Survey on Confinement during the COVID-19 Pandemic” to collect information on the American population practicing social distancing and some level of confinement. The survey collected information on demographics, duration and degree of confinement, and sleep-wake dynamics. The online survey was available for completion by any individual ≥18 years of age through the Penn Medicine Clinical Research page from May 16th to November 11th 2020. Descriptive statistics characterized the nature of confinement and non-parametric correlations evaluated the relationships between confinement and sleep-wake dynamics. Results N=226 participants completed the survey (n=176 female [77.8%]; n=47 male [20.8%]). The average age was 44.9±17.4 years. N=215[95.1%] reported confinement since March 2020 for an average of 89.3±41.7 days in confinement. Surveyed participants in confinement reported sleeping more than before confinement [40.0%], taking the same amount of time to fall asleep [56.6%], and felt that they were getting enough sleep [66.3%]. However, 36.3% of participants reported going to bed earlier and waking up earlier. Participants that engaged in naps prior to confinement reported taking more naps in confinement [50.8%]. Participants reported more daytime sleepiness [42.9%] and more disturbed sleep quality during confinement relative to before confinement [42.5%]. There were no significant correlations between time in confinement and sleep outcomes. Conclusion During the confinement amid the COVID-19 pandemic, participants responded by sleeping more and at different times, which could reflect circadian disruption of sleep. Changes in sleep amount and sleeping timing were accompanied by increased daytime sleepiness and a reduction in sleep quality. These changes may have been due to age, stressors experienced during the pandemic, social isolation, and/or a change in behavioral routines in response to changing demands and schedules. Our findings suggest that attention to changes in sleep-wake dynamics due to prolonged confinement is likely important to maintain healthy behaviors. Support (if any):

Astrocytic GABA Transporter controls sleep by modulating GABAergic signaling in Drosophila circadian neurons

A precise balance between sleep and wakefulness is essential to sustain a good quality of life and optimal brain function. GABA is known to play a key and conserved role in sleep control, and GABAergic tone should therefore be tightly controlled in sleep circuits. Here we examined the role of the astrocytic GABA transporter (GAT) in sleep regulation using Drosophila melanogaster. We found that a hypomorphic gat mutation (gat33-1) increased sleep amount, decreased sleep latency, and increased sleep consolidation. Interestingly, sleep defects were suppressed when gat33-1 was combined with a mutation disrupting wide-awake (wake), a gene that regulates the cell-surface levels of the GABAA receptor Resistance to Dieldrin (RDL) in the wake-promoting large ventral lateral neurons (l-LNvs). Moreover, RNAi knockdown of rdl and its modulator dnlg4 in these circadian neurons also suppressed gat33-1 sleep phenotypes. Brain immunohistochemistry showed that GAT-expressing astrocytes were located near RDL-positive l-LNvs cell bodies and dendritic processes. We conclude that astrocytic GAT decreases GABAergic tone and RDL activation in arousal promoting LNvs, thus determining proper sleep amount and quality in Drosophila

Is COVID-19 Keeping us Up at Night? Stress, Anxiety, and Sleep Among Adult Twins

In response to the COVID-19 pandemic, a variety of social distancing measures to mitigate the virus outbreak have been implemented. These measures may have unintended consequences on individuals’ well-being, such as increased stress, anxiety, and sleep disruptions. We investigated the extent to which individuals’ mental health status is associated with perceived changes in sleep amount and sleep quality among a sample of adult twin pairs (N = 909 pairs; 77% MZ, 23% DZ), less than a month after the outbreak was declared a pandemic by the World Health Organization. About half of participants reported no change in sleep amount (50.1%) or sleep quality (55.6%). Approximately one-third of the participants had increased amount of sleep (29.8%), and 32.9% reported a decrease in sleep quality. We found that stress and anxiety levels were associated with sleep reduction (ORs = 2.36 and 3.12 for stress and anxiety, respectively) and poorer sleep quality (ORs = 2.45 and 3.73 for stress and anxiety, respectively), even after taking into account between-family confounds. A much smaller association was observed between levels of stress and anxiety and increased sleep amount (ORs = 1.42 and 1.60 for stress and anxiety, respectively) and sleep quality (OR = 1.21 and 1.29 for stress and anxiety, respectively), which was no longer significant after controlling for between-family confounds. Our results demonstrate that stress and anxiety associated with the COVID-19 pandemic and social distancing measures may be linked to reduced sleep amount and quality.

Medial Parabrachial Nucleus Is Essential in Controlling Wakefulness in Rats

Activation of the parabrachial nucleus (PB) in the brainstem induced wakefulness in rats, suggesting which is an important nucleus that controls arousal. However, the sub-regions of PB in regulating sleep-wake cycle is still unclear. Here, we employ chemogenetics and optogenetics strategies and find that activation of the medial part of PB (MPB), but not the lateral part, induces continuous wakefulness for 10 h without sleep rebound in neither sleep amount nor the power spectra. Optogenetic activation of glutamatergic MPB neurons in sleeping rats immediately wake rats mediated by the basal forebrain (BF) and lateral hypothalamus (LH), but not the ventral medial thalamus. Most importantly, chemogenetic inhibition of PB neurons decreases wakefulness for 10 h. Conclusively, these findings indicate that the glutamatergic MPB neurons are essential in controlling wakefulness, and that MPB-BF and MPB-LH pathways are the major neuronal circuits.

Manipulations of the olfactory circuit highlight the role of sensory stimulation in regulating sleep amount

Study Objectives While wake duration is a major sleep driver, an important question is if wake quality also contributes to controlling sleep. In particular, we sought to determine whether changes in sensory stimulation affect sleep in Drosophila. As Drosophila rely heavily on their sense of smell, we focused on manipulating olfactory input and the olfactory sensory pathway. Methods Sensory deprivation was first performed by removing antennae or applying glue to antennae. We then measured sleep in response to neural activation, via TRPA1, or inhibition, via KIR2.1, of subpopulations of neurons in the olfactory pathway. Genetically restricting manipulations to adult animals prevented developmental effects. Results We find that olfactory deprivation reduces sleep, largely independently of mushroom bodies that integrate olfactory signals for memory consolidation and have previously been implicated in sleep. However, specific neurons in the lateral horn, the other third order target of olfactory input, affect sleep. Also, activation of inhibitory second order projection neurons increases sleep. No single neuronal population in the olfactory processing pathway was found to bidirectionally regulate sleep, and reduced sleep in response to olfactory deprivation may be masked by temperature changes. Conclusions These findings demonstrate that Drosophila sleep is sensitive to sensory stimulation, and identify novel sleep-regulating neurons in the olfactory circuit. Scaling of signals across the circuit may explain the lack of bidirectional effects when neuronal activity is manipulated. We propose that olfactory inputs act through specific circuit components to modulate sleep in flies.

Predictors of Sleep Recall Bias in College Students

College students are known to have unhealthy levels of sleep. Using data from the StudentLife Dataset, we analyzed the predictors of “recall bias” regarding sleep. We compared the average of a running, daily, self-reported sleep value over a period of time to the average sleep amount perceived by the students in their PSQI (Pittsburgh Sleep Quality Index) tests. We found that the variability in the measure of self-assessment of health was related to errors in sleep recall, as were some individual parameters.