Mindfulness-based therapy for insomnia for older adults with sleep difficulties: a randomized clinical trial.

OBJECTIVE: Poor sleep is a modifiable risk factor for multiple disorders. Frontline treatments (e.g. cognitive-behavioral therapy for insomnia) have limitations, prompting a search for alternative approaches. Here, we compare manualized Mindfulness-Based Therapy for Insomnia (MBTI) with a Sleep Hygiene, Education, and Exercise Program (SHEEP) in improving subjective and objective sleep outcomes in older adults. METHODS: We conducted a single-site, parallel-arm trial, with blinded assessments collected at baseline, post-intervention and 6-months follow-up. We randomized 127 participants aged 50-80, with a Pittsburgh Sleep Quality Index (PSQI) score ⩾5, to either MBTI (n = 65) or SHEEP (n = 62), both 2 hr weekly group sessions lasting 8 weeks. Primary outcomes included PSQI and Insomnia Severity Index, and actigraphy- and polysomnography-measured sleep onset latency (SOL) and wake after sleep onset (WASO). RESULTS: Intention-to-treat analysis showed reductions in insomnia severity in both groups [MBTI: Cohen's effect size d = -1.27, 95% confidence interval (CI) -1.61 to -0.89; SHEEP: d = -0.69, 95% CI -0.96 to -0.43], with significantly greater improvement in MBTI. Sleep quality improved equivalently in both groups (MBTI: d = -1.19; SHEEP: d = -1.02). No significant interaction effects were observed in objective sleep measures. However, only MBTI had reduced WASOactigraphy (MBTI: d = -0.30; SHEEP: d = 0.02), SOLactigraphy (MBTI: d = -0.25; SHEEP: d = -0.09), and WASOPSG (MBTI: d = -0.26; SHEEP (d = -0.18). There was no change in SOLPSG. No participants withdrew because of adverse effects. CONCLUSIONS: MBTI is effective at improving subjective and objective sleep quality in older adults, and could be a valid alternative for persons who have failed or do not have access to standard frontline therapies.

Short Sleep Duration in School-Age Children: Differential Factors on Weekdays and Weekends.

OBJECTIVES: To quantify school-age children's sleep and parent-associated factors on weekdays and weekends in Singapore, and investigate school-related and parent-related factors associated with short sleep. METHODS: In an online survey, 251 parents with a child aged 7-12 y in Singapore reported their child's sleep duration and school start time. Parent-related factors including sleep hygiene (e.g., parent-set bedtime), sleep priority (the amount of sleep respondents allowed their children to trade for other activities), and both parents' sleep durations, were also reported. RESULTS: The prevalence of short sleep among the children was 64.5% on weekdays and 19.5% on weekends. Children's sleep duration increased from 8.42 h on weekdays to 9.45 h on weekends (p < .001). Relative to weekdays, on weekends, parents showed similar increases in sleep durations (p < .001), imposed poorer sleep hygiene on their children (reduced likelihood of setting bedtimes and increased pre-bedtime electronic device use; p < .001), and allowed their children to trade more sleep for interacting with family and friends, social media, gaming, and TV / videos (p < .001). Shorter sleep duration in children was significantly associated with earlier school start time (B = 0.80, p = .02) and poorer sleep hygiene on weekdays (B = 0.16, p < .001), but lower sleep priority (B = 0.05, p = .002) and shorter parental sleep duration on weekends (maternal: B = 0.18, p < .001, paternal: B = 0.17, p = .002). CONCLUSIONS: Delaying school start times may be effective in increasing school-age children's sleep duration on weekdays, while family-based interventions designed to enhance sleep hygiene, priority of sleep over other activities, and parents' sleep durations can benefit children's sleep duration on both weekdays and weekends.

Neurobehavioural functions during variable and stable short sleep schedules.

We investigated whether variable sleep schedules might mitigate the neurobehavioural deficits induced by multiple nights of sleep restriction. In this 4-night experiment, 78 young adults (age: 18-28 years) were randomly assigned to four groups: 8888, 8666, 8846 and 8486, where each digit corresponded to time-in-bed in hours for each study night. After one baseline night of 8-hr time-in-bed, time-in-bed remained unchanged for the 8888 group, while the other groups had short sleep schedules (total time-in-bed = 18 hr) that differed in the number of time-in-bed changes. Sleep was monitored using actigraphy at home. Daytime neurobehavioural functions were assessed in the laboratory at single time points, after the baseline night, and again after 3 nights of the sleep manipulation period. For sustained attention, the 8888 group responded faster in the Psychomotor Vigilance Task after the manipulation period (p = .01), while responses became slower for the less variable sleep schedules (8666 and 8846; p < .01), but not the most variable sleep schedule (8486; p = .14). Processing speed also improved in the 8888 group and the variable 8846 and 8486 groups (p < .01), but not in the stable 8666 group (p = .09). Furthermore, subjective sleepiness was preserved in the 8888 and, importantly, 8486 groups (p > .05), but was elevated in the 8666 and 8846 groups (p < .05). These findings suggest that when sleep opportunities are limited across multiple nights, a variable sleep schedule that allows for prophylactic and/or recovery sleep on some nights may mitigate some daytime neurobehavioural deficits as compared with a schedule with no opportunity for recovery.

Longitudinal Changes in the Cerebral Cortex Functional Organization of Healthy Elderly.

Healthy aging is accompanied by disruptions in the functional modular organization of the human brain. Cross-sectional studies have shown age-related reductions in the functional segregation and distinctiveness of brain networks. However, less is known about the longitudinal changes in brain functional modular organization and their associations with aging-related cognitive decline. We examined age- and aging-related changes in functional architecture of the cerebral cortex using a dataset comprising a cross-sectional healthy young cohort of 57 individuals (mean ± SD age, 23.71 ± 3.61 years, 22 males) and a longitudinal healthy elderly cohort of 72 individuals (mean ± baseline age, 68.22 ± 5.80 years, 39 males) with 2-3 time points (18-24 months apart) of task-free fMRI data. We found both cross-sectional (elderly vs young) and longitudinal (in elderly) global decreases in network segregation (decreased local efficiency), integration (decreased global efficiency), and module distinctiveness (increased participation coefficient and decreased system segregation). At the modular level, whereas cross-sectional analyses revealed higher participation coefficient across all modules in the elderly compared with young participants, longitudinal analyses revealed focal longitudinal participation coefficient increases in three higher-order cognitive modules: control network, default mode network, and salience/ventral attention network. Cross-sectionally, elderly participants also showed worse attention performance with lower local efficiency and higher mean participation coefficient, and worse global cognitive performance with higher participation coefficient in the dorsal attention/control network. These findings suggest that healthy aging is associated with whole-brain connectome-wide changes in the functional modular organization of the brain, accompanied by loss of functional segregation, particularly in higher-order cognitive networks.SIGNIFICANCE STATEMENT Cross-sectional studies have demonstrated age-related reductions in the functional segregation and distinctiveness of brain networks. However, longitudinal aging-related changes in brain functional modular architecture and their links to cognitive decline remain relatively understudied. Using graph theoretical and community detection approaches to study task-free functional network changes in a cross-sectional young and longitudinal healthy elderly cohort, we showed that aging was associated with global declines in network segregation, integration, and module distinctiveness, and specific declines in distinctiveness of higher-order cognitive networks. Further, such functional network deterioration was associated with poorer cognitive performance cross-sectionally. Our findings suggest that healthy aging is associated with system-level changes in brain functional modular organization, accompanied by functional segregation loss particularly in higher-order networks specialized for cognition.

Trait-like characteristics of sleep EEG power spectra in adolescents across sleep opportunity manipulations.

The electroencephalographic power spectra of non-rapid eye movement sleep in adults demonstrate trait-like consistency within participants across multiple nights, even when prior sleep deprivation is present. Here, we examined the extent to which this finding applies to adolescents who are habitually sleep restricted on school-days and sleep longer on weekends. We evaluated 78 adolescents across three sleep restriction groups who underwent different permutations of adequate sleep (9 hr time-in-bed), sleep restriction (5 hr time-in-bed), afternoon naps (1 hr afternoon) and recovery sleep (9 hr time-in-bed) that simulate behaviour on school-days and weekends. The control group comprised a further 22 adolescents who had 9 hr of sleep opportunity each night. Intra-class correlation coefficients showed moderate to almost perfect within-subject stability in electroencephalographic power spectra across multiple nights in both sleep restriction and control groups, even when changes to sleep macrostructure were observed. While nocturnal intra-class correlation metrics were lower in the low-frequency and spindle frequency bins in the sleep restriction compared with the control group, hierarchical clustering measures could still identify multi-night electroencephalographic spectra as originating from the same individual. The trait-like characteristics of electroencephalographic spectra from an adolescent remain identifiable despite the disruptive effects of multi-night sleep restriction to sleep architecture.

Sex differences in the circadian regulation of sleep and waking cognition in humans.

The sleep-wake cycle and circadian rhythmicity both contribute to brain function, but whether this contribution differs between men and women and how it varies across cognitive domains and subjective dimensions has not been established. We examined the circadian and sleep-wake-dependent regulation of cognition in 16 men and 18 women in a forced desynchrony protocol and quantified the separate contributions of circadian phase, prior sleep, and elapsed time awake on cognition and sleep. The largest circadian effects were observed for reported sleepiness, mood, and reported effort; the effects on working memory and temporal processing were smaller. Although these effects were seen in both men and women, there were quantitative differences. The amplitude of the circadian modulation was larger in women in 11 of 39 performance measures so that their performance was more impaired in the early morning hours. Principal components analysis of the performance measures yielded three factors, accuracy, effort, and speed, which reflect core performance characteristics in a range of cognitive tasks and therefore are likely to be important for everyday performance. The largest circadian modulation was observed for effort, whereas accuracy exhibited the largest sex difference in circadian modulation. The sex differences in the circadian modulation of cognition could not be explained by sex differences in the circadian amplitude of plasma melatonin and electroencephalographic slow-wave activity. These data establish the impact of circadian rhythmicity and sex on waking cognition and have implications for understanding the regulation of brain function, cognition, and affect in shift-work, jetlag, and aging.

Functional segregation loss over time is moderated by APOE genotype in healthy elderly.

We investigated the influence of the apolipoprotein E-ɛ4 allele (APOE-ɛ4) on longitudinal age-related changes in brain functional connectivity (FC) and cognition, in view of mixed cross-sectional findings. One hundred and twenty-two healthy older adults (aged 58-79; 25 APOE-ɛ4 carriers) underwent task-free fMRI scans at baseline. Seventy-eight (16 carriers) had at least one follow-up (every 2 years). Changes in intra- and internetwork FCs among the default mode (DMN), executive control (ECN), and salience (SN) networks, as well as cognition, were quantified using linear mixed models. Cross-sectionally, APOE-ɛ4 carriers had lower functional connectivity between the ECN and SN than noncarriers. Carriers also showed a stronger age-dependent decrease in visuospatial memory performance. Longitudinally, carriers had steeper increase in inter-ECN-DMN FC, indicating loss of functional segregation. The longitudinal change in processing speed performance was not moderated by APOE-ɛ4 genotype, but the brain-cognition association was. In younger elderly, faster loss of segregation was correlated with greater decline in processing speed regardless of genotype. In older elderly, such relation remained for noncarriers but reversed for carriers. APOE-ɛ4 may alter aging by accelerating the change in segregation between high-level cognitive systems. Its modulation on the longitudinal brain-cognition relationship was age-dependent.

Weak social networks and restless sleep interrelate through depressed mood among elderly.

PURPOSE: Sleep disturbance is common in late life. While social interaction is a basic human concern, few studies have explored the linkage between interpersonal relationships and sleep disturbance. The present study examines the reciprocal associations between weak social networks outside the household and sleep disturbance in elderly, as well as the underlying mechanisms. METHODS: We utilized data from a nationally representative longitudinal survey of community-dwelling elderly in Singapore (n = 1417; ≥ 60 years). Participants were assessed three times over 6 years (2009, 2011, 2015). Measures included strength of social networks outside the household, restless sleep (sleep disturbance), and the mediating variables of depressed mood, chronic diseases, and cognitive impairment. A cross-lagged mediation analysis was conducted. RESULTS: Bootstrapping results showed that weaker social networks were related to more restless sleep via more depressed mood. Also, restless sleep was negatively associated with social networks through depressed mood. The other mediators examined were not significant. CONCLUSIONS: Weak social networks and restless sleep reciprocally influence each other through depressed mood. Recognition of this interplay can inform efforts in improving elderly's sleep quality, social networks, and psychological well-being.

Importance of social relationships in the association between sleep duration and cognitive function: data from community-dwelling older Singaporeans.

ABSTRACTBackground:Aging is accompanied by cognitive decline that is escalated in older adults reporting extreme sleep duration. Social relationships can influence health outcomes and thus may qualify the association between sleep duration and cognitive function. The present study examines the moderating effects of marital status, household size, and social network with friends and relatives on the sleep-cognition association among older adults. METHODS: Data (N = 4,169) came from the Social Isolation, Health, and Lifestyles Survey, a nationally representative survey of community-dwelling older Singaporeans (≥ 60 years). Sleep duration and social relationships were self-reported. Cognitive function was assessed with the Short Portable Mental Status Questionnaire. RESULTS: Regression analysis revealed that the inverted U-shaped association between sleep duration and cognitive function was less profound among older adults who were married (vs. unmarried) and those who had stronger (vs. weaker) social networks. In contrast, it was more prominent among individuals who had more (vs. fewer) household members. CONCLUSIONS: Being married and having stronger social networks may buffer against the negative cognitive impact of extreme sleep duration. But larger household size might imply more stress for older persons, and therefore strengthen the sleep duration-cognitive function association. We discuss the potential biological underpinnings and the policy implications of the findings. Although our findings are based on a large sample, replication studies using objective measures of sleep duration and other cognitive measures are needed.

Longitudinal brain structure and cognitive changes over 8 years in an East Asian cohort.

Although East Asia harbors the largest number of aging adults in the world, there is currently little data clarifying the longitudinal brain-cognition relationships in this group. Here, we report structural MRI and neuropsychological findings from relatively healthy Chinese older adults of the Singapore-Longitudinal Aging Brain Study cohort over 8 years of follow up (n=111, mean age=67.1 years, range=56.1-83.1 years at baseline). Aging-related change in structural volume was observed, with total cerebral atrophy at -0.56%/year, hippocampal atrophy at -0.94%/year and ventricular expansion at 3.56%/year. Only speed of processing showed an aging-related decline, while other cognitive domains were relatively maintained. Faster decline in global cognition was associated with total cerebral, hippocampal and gray matter volume losses over time. Faster total cerebral atrophy and white matter atrophy (frontal and parietal regions) was associated with faster decline in verbal memory. Hippocampal atrophy and ventricular expansion were both associated with greater decline in verbal memory and executive function. Our findings provide a benchmark for research on brain structural and cognitive changes with aging in East Asians.

Assessing the benefits of napping and short rest breaks on processing speed in sleep-restricted adolescents.

Achievement-oriented adolescents often study long hours under conditions of chronic sleep restriction, adversely affecting cognitive function. Here, we studied how napping and rest breaks (interleaved off-task periods) might ameliorate the negative effects of sleep restriction on processing speed. Fifty-seven healthy adolescents (26 female, age = 15-19 years) participated in a 15-day live-in protocol. All participants underwent sleep restriction (5 h time-in-bed), but were then randomized into two groups: one of these groups received a daily 1-h nap opportunity. Data from seven of the study days (sleep restriction days 1-5, and recovery days 1-2) are reported here. The Blocked Symbol Decoding Test, administered once a day, was used to assess time-on-task effects and the effects of rest breaks on processing speed. Controlling for baseline differences, participants who took a nap demonstrated faster speed of processing and greater benefit across testing sessions from practice. These participants were also affected significantly less by time-on-task effects. In contrast, participants who did not receive a nap benefited more from the rest breaks that were permitted between blocks of the test. Our results indicate that napping partially reverses the detrimental effects of sleep restriction on processing speed. However, rest breaks have a greater effect as a countermeasure against poor performance when sleep pressure is higher. These data add to the growing body of evidence showing the importance of sleep for good cognitive functioning in adolescents, and suggest that more frequent rest breaks might be important in situations where sleep loss is unavoidable.

Factors of nocturnal sleep and daytime nap durations in community-dwelling elderly: a longitudinal population-based study.

BACKGROUND: Durations of nocturnal sleep and daytime nap influence the well-being of older adults. It is thus essential to understand their determinants. However, much previous research did not assess sleep duration and nap duration individually, and longitudinal data is lacking. This study aimed at examining the impact of demographic, psychosocial, and health factors, including ethnicity, social networks outside the household, smoking and physical exercise on sleep duration and nap duration among community-dwelling elderly. METHODS: Our study involved over 2,600 older adults (≥60 years) from a longitudinal, nationally representative survey - the Panel on Health and Ageing of Singaporean Elderly. Sleep and nap durations at Time 2 (two years later) were regressed on predictors measured at Time 1. RESULTS: Time 2 short nocturnal sleep duration was predicted by Malay ethnicity (relative to Chinese and Indian), older age, lower education level, more depressive symptoms, and obesity, whereas future long nocturnal sleep duration was predicted by weaker social networks, older age, and more chronic diseases. Furthermore, smoking, obesity, Malay or Indian (relative to Chinese), older age, male gender, and cognitive impairment predicted longer daytime nap duration in the future. CONCLUSIONS: Older adults' nocturnal sleep and daytime nap durations may be affected by different demographic, psychosocial, and health factors. Thus, it is important to differentiate these two attributes in this age group.

Reduced functional segregation between the default mode network and the executive control network in healthy older adults: A longitudinal study.

The effects of age on functional connectivity (FC) of intrinsic connectivity networks (ICNs) have largely been derived from cross-sectional studies. Far less is known about longitudinal changes in FC and how they relate to ageing-related cognitive decline. We evaluated intra- and inter-network FC in 78 healthy older adults two or three times over a period of 4years. Using linear mixed modeling we found progressive loss of functional specialization with ageing, evidenced by a decline in intra-network FC within the executive control (ECN) and default mode networks (DMN). In contrast, longitudinal inter-network FC between ECN and DMN showed a u-shaped trajectory whereby functional segregation between these two networks initially increased over time and later decreased as participants aged. The rate of loss in functional segregation between ECN and DMN was associated with ageing-related decline in processing speed. The observed longitudinal FC changes and their associations with processing speed remained after correcting for longitudinal reduction in gray matter volume. These findings help connect ageing-related changes in FC with ageing-related decline in cognitive performance and underscore the value of collecting concurrent longitudinal imaging and behavioral data.

Sleep restriction can attenuate prioritization benefits on declarative memory consolidation.

As chronic sleep restriction is a widespread problem among adolescents, the present study investigated the effects of a 1-week sleep restriction (SR) versus control period on the consolidation of long-term memory for prose passages. We also determined whether the benefit of prioritization on memory is modulated by adequate sleep occurring during consolidation. Fifty-six healthy adolescents (25 male, aged 15-19 years) were instructed to remember a prose passage in which half of the content was highlighted (prioritized), and were told that they would receive an additional bonus for remembering highlighted content. Following an initial free recall test, participants underwent a 7-night period in which they received either a 5-h (SR) or 9-h (control) nightly sleep opportunity, monitored by polysomnography on selected nights. Free recall of the passage was tested at the end of the sleep manipulation period (1 week after encoding), and again 6 weeks after encoding. Recall of highlighted content was superior to that of non-highlighted content at all three time-points (initial, 1 week, 6 weeks). This beneficial effect of prioritization on memory was stronger 1 week relative to a few minutes after encoding for the control, but not the SR group. N3 duration was similar in the control and SR groups. Overall, the present study shows that the benefits of prioritization on memory are enhanced over time, requiring time and sleep to unfold fully. Partial sleep deprivation (i.e. 5-h nocturnal sleep opportunity) may attenuate such benefits, but this may be offset by preservation of N3 sleep duration.

Sleep deprivation increases formation of false memory.

Retrieving false information can have serious consequences. Sleep is important for memory, but voluntary sleep curtailment is becoming more rampant. Here, the misinformation paradigm was used to investigate false memory formation after 1 night of total sleep deprivation in healthy young adults (N = 58, mean age ± SD = 22.10 ± 1.60 years; 29 males), and 7 nights of partial sleep deprivation (5 h sleep opportunity) in these young adults and healthy adolescents (N = 54, mean age ± SD = 16.67 ± 1.03 years; 25 males). In both age groups, sleep-deprived individuals were more likely than well-rested persons to incorporate misleading post-event information into their responses during memory retrieval (P < 0.050). These findings reiterate the importance of adequate sleep in optimal cognitive functioning, reveal the vulnerability of adolescents' memory during sleep curtailment, and suggest the need to assess eyewitnesses' sleep history after encountering misleading information.

Effects of insufficient sleep on circadian rhythmicity and expression amplitude of the human blood transcriptome.

Insufficient sleep and circadian rhythm disruption are associated with negative health outcomes, including obesity, cardiovascular disease, and cognitive impairment, but the mechanisms involved remain largely unexplored. Twenty-six participants were exposed to 1 wk of insufficient sleep (sleep-restriction condition 5.70 h, SEM = 0.03 sleep per 24 h) and 1 wk of sufficient sleep (control condition 8.50 h sleep, SEM = 0.11). Immediately following each condition, 10 whole-blood RNA samples were collected from each participant, while controlling for the effects of light, activity, and food, during a period of total sleep deprivation. Transcriptome analysis revealed that 711 genes were up- or down-regulated by insufficient sleep. Insufficient sleep also reduced the number of genes with a circadian expression profile from 1,855 to 1,481, reduced the circadian amplitude of these genes, and led to an increase in the number of genes that responded to subsequent total sleep deprivation from 122 to 856. Genes affected by insufficient sleep were associated with circadian rhythms (PER1, PER2, PER3, CRY2, CLOCK, NR1D1, NR1D2, RORA, DEC1, CSNK1E), sleep homeostasis (IL6, STAT3, KCNV2, CAMK2D), oxidative stress (PRDX2, PRDX5), and metabolism (SLC2A3, SLC2A5, GHRL, ABCA1). Biological processes affected included chromatin modification, gene-expression regulation, macromolecular metabolism, and inflammatory, immune and stress responses. Thus, insufficient sleep affects the human blood transcriptome, disrupts its circadian regulation, and intensifies the effects of acute total sleep deprivation. The identified biological processes may be involved with the negative effects of sleep loss on health, and highlight the interrelatedness of sleep homeostasis, circadian rhythmicity, and metabolism.

Differential age-dependent associations of gray matter volume and white matter integrity with processing speed in healthy older adults.

Slower processing speed (PS), a highly robust feature of cognitive aging, is associated with white matter (WM) deterioration and gray matter volume (GMV) loss. Traditional linear regression models assume a constant relationship between brain structure and cognition over time. To probe for variation in the association between WM and GMV and PS over time, we used a novel sparse varying coefficient model on data collected from 126 relatively healthy older adults (67 females, aged 58-85years) evaluated with MRI and a standardized neuropsychological test-battery. We found that WM microstructural differences indexed by fractional anisotropy values in the fronto-striatal tracts (internal and external capsule) showed a stronger association with PS before the age of 70years. Contrastingly, GMV values of the left putamen and middle occipital gyrus were more strongly correlated with PS after 70years. Additionally, within GM and WM compartments, there was heterogeneity in the temporal sequence in which different cortical and subcortical elements were most strongly associated with PS. Together, these observations provide a more nuanced account of the relationships between different structural components of the aging brain and processing speed, a key cognitive domain affected in relatively healthy older adults.

Neurobehavioral functions during recurrent periods of sleep restriction: effects of intra-individual variability in sleep duration.

STUDY OBJECTIVES: To investigate whether neurobehavioral impairments are exacerbated during successive cycles of sleep restriction and recovery in young adults, and whether a variable short sleep schedule can mitigate these impairments relative to a stable one. METHODS: Fifty-two healthy young adults (25 males, aged: 21-28) were randomly assigned to the stable short sleep group, the variable short sleep group, or the control group in this laboratory-based study. They underwent two baseline nights of 8-hour time-in-bed (TIB), followed by two cycles of "weekday" sleep opportunity manipulation and "weekend" recovery (8-hour TIB). During each manipulation period, the stable short sleep and the control groups received 6- and 8-hour TIBs each night respectively, while the variable short sleep group received 8-hour, 4-hour, 8-hour, 4-hour, and 6-hour TIBs from the first to the fifth night. Neurobehavioral functions were assessed five times each day. RESULTS: The stable short sleep group showed faster vigilance deterioration in the second week of sleep restriction as compared to the first. This effect was not observed in the variable short sleep group. Subjective alertness and practice-based improvement in processing speed were attenuated in both short sleep groups. CONCLUSIONS: In young adults, more variable short sleep schedules incorporating days of prophylactic or recovery sleep might mitigate compounding vigilance deficits resulting from recurrent cycles of sleep restriction. However, processing speed and subjective sleepiness were still impaired in both short sleep schedules. Getting sufficient sleep consistently is the only way to ensure optimal neurobehavioral functioning. CLINICAL TRIAL: Performance, Mood, and Brain and Metabolic Functions During Different Sleep Schedules (STAVAR), https://www.clinicaltrials.gov/study/NCT04731662, NCT04731662.

Assessment of circadian rhythms in humans: comparison of real-time fibroblast reporter imaging with plasma melatonin.

We compared the period of the rhythm of plasma melatonin, driven by the hypothalamic circadian pacemaker, to in vitro periodicity in cultured peripheral fibroblasts to assess the effects on these rhythms of a polymorphism of PER3 (rs57875989), which is associated with sleep timing. In vitro circadian period was determined using luminometry of cultured fibroblasts, in which the expression of firefly luciferase was driven by the promoter of the circadian gene Arntl (Bmal1). The period of the melatonin rhythm was assessed in a 9-d forced desynchrony protocol, minimizing confounding effects of sleep-wake and light-dark cycles on circadian rhythmicity. In vitro periods (32 participants, 24.61±0.33 h, mean±SD) were longer than in vivo periods (31 participants, 24.16±0.17 h; P<0.0001) but did not differ between PER3 genotypes (P>0.4). Analyses of replicate in vitro assessments demonstrated that circadian period was reproducible within individuals (intraclass correlation=0.62), but in vivo and in vitro period assessments did not correlate (P>0.9). In accordance with circadian entrainment theory, in vivo period correlated with the timing of melatonin (P<0.05) at baseline and with diurnal preference (P<0.05). Individual circadian rhythms can be reliably assessed in fibroblasts but may not correlate with physiological rhythms driven by the central circadian pacemaker.

Circadian period and the timing of melatonin onset in men and women: predictors of sleep during the weekend and in the laboratory.

Sleep complaints and irregular sleep patterns, such as curtailed sleep during workdays and longer and later sleep during weekends, are common. It is often implied that differences in circadian period and in entrained phase contribute to these patterns, but few data are available. We assessed parameters of the circadian rhythm of melatonin at baseline and in a forced desynchrony protocol in 35 participants (18 women) with no sleep disorders. Circadian period varied between 23 h 50 min and 24 h 31 min, and correlated positively (n = 31, rs  = 0.43, P = 0.017) with the timing of the melatonin rhythm relative to habitual bedtime. The phase of the melatonin rhythm correlated with the Insomnia Severity Index (n = 35, rs  = 0.47, P = 0.004). Self-reported time in bed during free days also correlated with the timing of the melatonin rhythm (n = 35, rs  = 0.43, P = 0.01) as well as with the circadian period (n = 31, rs  = 0.47, P = 0.007), such that individuals with a more delayed melatonin rhythm or a longer circadian period reported longer sleep during the weekend. The increase in time in bed during the free days correlated positively with circadian period (n = 31, rs  = 0.54, P = 0.002). Polysomnographically assessed latency to persistent sleep (n = 34, rs  = 0.48, P = 0.004) correlated with the timing of the melatonin rhythm when participants were sleeping at their habitual bedtimes in the laboratory. This correlation was significantly stronger in women than in men (Z = 2.38, P = 0.017). The findings show that individual differences in circadian period and phase of the melatonin rhythm associate with differences in sleep, and suggest that individuals with a long circadian period may be at risk of developing sleep problems.