Altered Sleep Homeostasis in Rev-erbα Knockout Mice.

STUDY OBJECTIVES: The nuclear receptor REV-ERBα is a potent, constitutive transcriptional repressor critical for the regulation of key circadian and metabolic genes. Recently, REV-ERBα's involvement in learning, neurogenesis, mood, and dopamine turnover was demonstrated suggesting a specific role in central nervous system functioning. We have previously shown that the brain expression of several core clock genes, including Rev-erbα, is modulated by sleep loss. We here test the consequences of a loss of REV-ERBα on the homeostatic regulation of sleep. METHODS: EEG/EMG signals were recorded in Rev-erbα knockout (KO) mice and their wild type (WT) littermates during baseline, sleep deprivation, and recovery. Cortical gene expression measurements after sleep deprivation were contrasted to baseline. RESULTS: Although baseline sleep/wake duration was remarkably similar, KO mice showed an advance of the sleep/wake distribution relative to the light-dark cycle. After sleep onset in baseline and after sleep deprivation, both EEG delta power (1-4 Hz) and sleep consolidation were reduced in KO mice indicating a slower increase of homeostatic sleep need during wakefulness. This slower increase might relate to the smaller increase in theta and gamma power observed in the waking EEG prior to sleep onset under both conditions. Indeed, the increased theta activity during wakefulness predicted delta power in subsequent NREM sleep. Lack of Rev-erbα increased Bmal1, Npas2, Clock, and Fabp7 expression, confirming the direct regulation of these genes by REV-ERBα also in the brain. CONCLUSIONS: Our results add further proof to the notion that clock genes are involved in sleep homeostasis. Because accumulating evidence directly links REV-ERBα to dopamine signaling the altered homeostatic regulation of sleep reported here are discussed in that context.

Sleep patterns and sleep-related complaints of Brazilian interstate bus drivers

Sleep-related complaints have become a highlight for physicians as well as public health administrators. Studies of sleep patterns and sleep-related complaints of shift workers have been useful in minimizing reduction in the quality of life due to the warping of the sleep-wake cycle. The objective of the present study was to assess patterns of sleep, sleep-related complaints as well as physical activity and scoring rates for depression and anxiety in interstate bus drivers. Data were obtained with a sleep questionnaire, with the Beck inventory for depression, and the State-Trait Anxiety Inventory (STAI). A total of 400 interstate bus drivers from the northern, southern, central-western and south-eastern regions of Brazil were interviewed. Sixty percent of the subjects interviewed presented at least one sleep-related complaint, 16% admitted to have dozed at the wheel while on duty, and 41% stated that they exercised on a regular basis. Other sleep disturbance complaints reported were: sleep latency 29'17"; physical fatigue, 59.8%; mental fatigue, 45.4%; sleepiness, 25.8%; irritability, 20.6%; insomnia, 37.5%, respiratory disturbances, 19.25% and snoring, 20.75%. Scores for anxiety and depression were not in the pathological range. The present data reinforce the view that bus drivers are generally discontent with shift work and its effects on sleep. Consequently, it is very important to establish an appropriate work schedule for drivers, besides implementing photo-therapy and physical activities in order to minimize sleepiness when driving.

Paradoxical sleep deprivation increases plasma endothelin levels

The endothelins (ET-1, 2 and 3) constitute a family of 21 amino acid peptides with potent biological activities. ET-1 is one of the most potent endogenous vasoconstrictors so far identified and its increased concentration in plasma appears to be closely related to the pathogenesis of arterial hypertension as well as to obstructive sleep apnea (OSA). OSA patients exhibit repetitive episodes of apnea and hypopnea that result in hypoxia and consecutive arousals. These patients are chronically sleep deprived, which may aggravate the hypertensive features, since literature data show that sleep deprivation results in hypertension both in humans and in animals. Based on the reported relationship between ET-1, hypertension and sleep deprivation consequences, the purpose of the present study was to determine plasma ET concentrations in paradoxical sleep-deprived animals. Male Wistar rats, 3 to 4 months old (N = 10 per group), were deprived of sleep for 24 and 96 h by the platform technique and plasma ET-1/2 was measured by radioimmunoassay. Analysis of plasma revealed that 96 h of sleep deprivation induced a significant increase in ET-1/2 release (6.58 fmol/ml) compared to control (5.07 fmol/ml). These data show that sleep deprivation altered plasma ET-1/2 concentrations, suggesting that such an increase may participate in the genesis of arterial hypertension and cardiorespiratory changes observed after sleep deprivation.

Sleep disorders, sleepiness and traffic safety: a public health menace

Sleep disorders are not uncommon and have been widely reported throughout the world. They have a profound impact on industrialized 24-h societies. Consequences of these problems include impaired social and recreational activities, increased human errors, loss of productivity, and elevated risk of accidents. Conditions such as acute and chronic insomnia, sleep loss, excessive sleepiness, shift-work, jet lag, narcolepsy, and sleep apnea warrant public health attention, since residual sleepiness during the day may affect performance of daily activities such as driving a car. Benzodiazepine hypnotics and zopiclone promote sleep, both having residual effects the following day including sleepiness and reduced alertness. In contrast, the non-benzodiazepine hypnotics zolpidem and zaleplon have no significant next-day residual effects when taken as recommended. Research on the effects of wakefulness-promoting drugs on driving ability is limited. Countermeasures for excessive daytime sleepiness have a limited effect. There is a need for a social awareness program to educate the public about the potential consequences of various sleep disorders such as narcolepsy, sleep apnea, shift-work-related sleep loss, and excessive daytime sleepiness in order to reduce the number of sleep-related traffic accidents.

Sleep habits and complaints of adults in the city of São Paulo, Brazil, in 1987 and 1995

This study compares the prevalence of complaints of insomnia, excessive diurnal sleepiness, parasomnias, and sleep habits of the adult population in the city of São Paulo, Brazil, estimated in surveys carried out in 1987 and 1995. Representative samples of 1000 adult residents per survey were interviewed using a validated structured sleep questionnaire, the "UNIFESP Sleep Questionnaire". Difficulty maintaining sleep, difficulty initiating sleep and early morning awakening, occurring at least three times a week, were reported in 1987 and 1995, by 15.8/27.6, 13.9/19.1, and 10.6/14.2% of the interviewees, respectively, significantly increasing throughout time. These sleep problems were more often found among women. Frequencies of excessive diurnal sleepiness and sleep attacks were unchanged comparing 1987 with 1995 (4.5 vs 3.8 and 3.1 vs 3.0%, respectively). Parasomnia complaints remained unchanged, with the exception of leg cramps, which doubled in prevalence from 1987 to 1995 (2.6 to 5.8%). Snoring was the most common parasomnia (21.5% in 1995), reported more often by men than by women, and somnambulism was the least common (approximately 1%). Besides sleeping slightly less, interviewees went to bed and woke up later in 1995. Approximately 12% of the subjects in both surveys had consulted a physician due to sleep problems and 3.0% reported habitual use of sleep-promoting substances in 1995. Overall, there was a significant increase in insomnia complaints from 1987 to 1995 in the general population of the city of São Paulo. This major change over a little under a decade should be considered as an important public health issue.

Information processing in sleep-onset insomnia : a test of the neurocognitive model /

The present thesis study is a systematic investigation of information processing at sleep onset, using auditory event-related potentials (ERPs) as a test of the neurocognitive model of insomnia. Insomnia is an extremely prevalent disorder in society resulting in problems with daytime functioning (e.g., memory, concentration, job performance, mood, job and driving safety). Various models have been put forth in an effort to better understand the etiology and pathophysiology of this disorder. One of the newer models, the neurocognitive model of insomnia, suggests that chronic insomnia occurs through conditioned central nervous system arousal. This arousal is reflected through increased information processing which may interfere with sleep initiation or maintenance. The present thesis employed event-related potentials as a direct method to test information processing during the sleep-onset period. Thirteen poor sleepers with sleep-onset insomnia and 1 2 good sleepers participated in the present study. All poor sleepers met the diagnostic criteria for psychophysiological insomnia and had a complaint of problems with sleep initiation. All good sleepers reported no trouble sleeping and no excessive daytime sleepiness. Good and poor sleepers spent two nights at the Brock University Sleep Research Laboratory. The first night was used to screen for sleep disorders; the second night was used to investigate information processing during the sleep-onset period. Both groups underwent a repeated sleep-onsets task during which an auditory oddball paradigm was delivered. Participants signalled detection of a higher pitch target tone with a button press as they fell asleep. In addition, waking alert ERPs were recorded 1 hour before and after sleep on both Nights 1 and 2.As predicted by the neurocognitive model of insomnia, increased CNS activity was found in the poor sleepers; this was reflected by their smaller amplitude P2 component seen during wake of the sleep-onset period. Unlike the P2 component, the Nl, N350, and P300 did not vary between the groups. The smaller P2 seen in our poor sleepers indicates that they have a deficit in the sleep initiation processes. Specifically, poor sleepers do not disengage their attention from the outside environment to the same extent as good sleepers during the sleep-onset period. The lack of findings for the N350 suggest that this sleep component may be intact in those with insomnia and that it is the waking components (i.e., Nl, P2) that may be leading to the deficit in sleep initiation. Further, it may be that the mechanism responsible for the disruption of sleep initiation in the poor sleepers is most reflected by the P2 component. Future research investigating ERPs in insomnia should focus on the identification of the components most sensitive to sleep disruption. As well, methods should be developed in order to more clearly identify the various types of insomnia populations in research contexts (e.g., psychophysiological vs. sleep-state misperception) and the various individual (personality characteristics, motivation) and environmental factors (arousal-related variables) that influence particular ERP components. Insomnia has serious consequences for health, safety, and daytime functioning, thus research efforts should continue in order to help alleviate this highly prevalent condition.

An electrophysiological examination of intentional and inadvertent sleep onset : the effect of intention on the sleep onset process

The main purpose ofthis study was to examine the effect ofintention on the sleep onset process from an electrophysiological point ofview. To test this, two nap conditions, the Multiple Sleep Latency Test (MSLT) and the Repeated Test of Sustained Wakefulness (RTSW) were used to compare intentional and inadvertent sleep onset. Sixteen female participants (aged 19-25) spent two non-consecutive nights in the sleep lab; however, due to physical and technical difficulties only 8 participants produced compete sets of data for analysis. Each night participants were given six nap opportunities. For three ofthese naps they were instructed to fall asleep (MSLT), for the remaining three naps they were to attempt to remain awake (RTSW). These two types of nap opportunities represented the conditions ofintentional (MSLT) and inadvertent (RTSW) sleep onset. Several other sleepiness, performance, arousal and questionnaire measures were obtained to evaluate and/or control for demand characteristics, subjective effort and mental activity during the nap tests. The nap opportunities were scored using a new 9 stage scoring system developed by Hori et al. (1994). Power spectral analyses (FFT) were also performed on the sleep onset data provided by the two nap conditions. Longer sleep onset latencies (approximately 1.25 minutes) were obseIVed in the RTSW than the MSLT. A higher incidence of structured mental activity was reported in the RTSW and may have been reflected in higher Beta power during the RTSW. The decent into sleep was more ragged in the RTSW as evidenced by an increased number shifts towards higher arousal as measured using the Hori 9 stage sleep scoring method. 1ll The sleep onset process also appears to be altered by the intention to remain awake, at least until the point ofinitial Stage 2 sleep (i.e. the first appearance of spindle activity). When only examining the final 4.3 minutes ofthe sleep onset process (ending with spindle activity), there were significant interactions between the type ofnap and the time until sleep onset for Theta, Alpha and Beta power. That is to say, the pattern of spectral power measurements in these bands differed across time as a function ofthe type ofnap. The effect ofintention however, was quite small (,,2 < .04) when compared to the variance which could be accounted for by the passage oftime (,,2 == .10 to .59). These data indicate that intention alone cannot greatly extend voluntary wakefulness if a person is sleepy. This has serious implications for people who may be required to perform dangerous tasks while sleepy, particularly for people who are in a situation that does not allow them the opportunity to engage in behavioural strategies in order to maintain their arousal.

Longitudinal evaluation of sleep-related breathing disorders in an orthodontic population

Introduction: Les troubles respiratoires du sommeil (TRS), qui représentent une préoccupation croissante pour la santé, ont des effets significatifs sur la santé, le comportement et la performance académique chez l’enfant. Les malformations craniofaciales, l’hypertrophie adéno-amygdalienne et l'obésité, représentent des facteurs de risque importants dans le développement de cette condition. Les symptômes des TRS ont été étudiés dans une étude prospective chez les enfants et adolescents durant leur traitement orthodontique dans un milieu universitaire. Cette étude a cherché à décrire la prévalence et les facteurs de risque principaux des TRS, ainsi que l'impact des différentes interventions orthodontiques sur les symptômes TRS. Matériel et méthodes: dans une étude cohorte prospective, un groupe de 168 sujets âgés de 12 à 21 ans ont été soumis, quatre ans après la prise de données initiale, à un examen craniofacial en plus d'être administré des questionnaires qui ont recueilli des données sur la situation socio-démographique, le bruxisme et les troubles d’ATM, le sommeil et le comportement diurne, et les facteurs neuropsychologiques. Résultats: l'indice de masse corporelle a été augmenté mais est demeurée dans la même catégorie aux deux moments de l'enquête. Il ya eu une augmentation du serrement des dents et des symptômes de l'ATM, une diminution de la taille des amygdales, et une augmentation de la somnolence diurne. La prévalence des TRS n'a pas changé entre l’étude initiale et l’étude de suivi. Aucune intervention orthodontique s'est avérée avoir un effet cliniquement significatif sur les voies aériennes supérieures. Conclusions: la prévalence des symptômes TRS était constante par rapport aux valeurs de base pour la population étudiée, mais a augmenté si rapportée à la population générale. Les traitements orthodontiques ne montrent aucun effet sur les TRS. Mots-clés : apnée du sommeil, craniofacial, prévalence, ronflement, traitement orthodontique, voies aériennes supérieures

Maternal psychosocial adversity and the longitudinal development of infant sleep

Research has identified associations between indicators of social disadvantage and the presence of child sleep problems. We examined the longitudinal development of infant sleep in families experiencing high (n = 58) or low (n = 64) levels of psychosocial adversity, and the contributions of neonatal self-regulatory capacities and maternal settling strategies to this development. Assessments of infant sleep at 4-, 7-, and 12-weeks postpartum indicated no differences in sleeping difficulties between high- and low-adversity groups. However, more infant sleep difficulties were reported in the high- versus low-adversity groups at 12- and 18-month follow-ups. Neonatal self-regulatory capacities were not related to the presence or absence of adversity, or to subsequent infant sleep quality. However, there were group differences in maternal settling strategies that did predict subsequent infant sleep difficulties. The pattern of sleep disturbance observed in association with maternal psychosocial adversity at 18-months was consistent with risk for broader impairments in child functioning.

The relationship between parent and child dysfunctional beliefs about sleep and child sleep

Cognitive theories emphasise the role of dysfunctional beliefs about sleep in the development and maintenance of sleep-related problems (SRPs). The present research examines how parents' dysfunctional beliefs about children's sleep and child dysfunctional beliefs about sleep are related to each other and to children's subjective and objective sleep. Participants were 45 children aged 11 -12 years and their parents. Self-report measures of dysfunctional beliefs about sleep and child sleep were completed by children, mothers and fathers. Objective measures of child sleep were taken using actigraphy. The results showed that child dysfunctional beliefs about sleep were correlated with father (r=.43, p<.05) and mother (r=.43, p<.05) reported child SRPs, and with Sleep Onset Latency (r=.34, p<.05). Maternal dysfunctional beliefs about child sleep were related to child SRPs as reported by mothers (r=.44, p<.05), and to child dysfunctional beliefs about sleep (r=.37, p<.05). Some initial evidence was found for a mediation pathway in which child dyfunctional beliefs mediate the relationship between parent dysfunctional beliefs and child sleep. The results support the cognitive model of SRPs and contribute to the literature by providing the first evidence of familial aggregation of dysfunctional beliefs about sleep.

"When I go to bed hungry and sleep, I'm not hungry": children and parents' experiences of food insecurity

Evidence demonstrates food insecurity has a detrimental impact on a range of outcomes for children, but little research has been conducted in the UK, and children have rarely been asked to describe their experiences directly. We examined the experiences of food insecure families living in South London. Our mixed-methods approach comprised a survey of parents (n = 72) and one-to-one semi-structured interviews with children aged 5-11 years (n = 19). The majority of parents (86%) described their food security during the preceding year as very low. Most reported they had often or sometimes had insufficient food, and almost all had worried about running out of food. Two thirds of parents had gone hungry. Most parents reported they had been unable to afford a nutritionally balanced diet for their children, and just under half reported that their children had gone hungry. Four themes emerged from the interviews with children: sources of food; security of food, nutritional quality of food, and experiences of hunger. Children's descriptions of insufficient food being available indicate that parents are not always able to shield them from the impact of food insecurity. The lack of school-meals and after-school clubs serving food made weekends particularly problematic for some children. A notable consequence of food insecurity appears to be reliance on low-cost takeaway food, likely to be nutritionally poor.

Not all adolescents are sleep deprived: A study of rural populations

The objective of this study was to investigate the role of environmental factors in sleep duration among adolescents living in rural areas. A total of 1140 students (569 males), aged 10-19 years, and attending two schools in rural regions in southern Brazil, completed a questionnaire about their sleep habits. Demographic data were also obtained. Prevalence ratios (PR) were estimated for the cases of more than 9 h of sleep on weekdays. Sleep duration in adolescents with and without electric lighting at home was analyzed. Average sleep duration at night was 9.63 (1.64) h on school-going days and 10.14 (2.42) h on weekends. The prevalence of adolescents sleeping for more than 9 h at night on school-going days was 58.3%. Older adolescents showed a tendency to delay their sleep onset times, which is associated with a reduction of sleep duration. Adolescents without electric lighting at home slept longer on school-going days (P < 0.001) and on weekends (P = 0.013) when compared to those with electric lighting at home. From multivariate analysis, age (P < 0.001), school schedule (P = 0.007) and work (0.042) were factors affecting sleep duration. In contrast to the data previously reported for urban populations, we found a high prevalence of adolescents sleeping for more than 9 h on school nights. Data on populations living in less industrialized regions reinforce the idea that technological advances are associated with the negative impact of sleep phase delay in adolescents.

Association between rhythmic masticatory muscle activity during sleep and masticatory myofascial pain: A polysomnographic study

Aims: To test for an association between rhythmic masticatory muscle activity during sleep, as assessed according to polysomnographic criteria for sleep bruxism (RMMA-SB), and myofascial pain (MFP), as well as the chance of occurrence of MFP in patients with RMMA-SB. Methods: Thirty MFP patients (diagnosed according to the Research Diagnostic Criteria for Temporomandibular Disorders) and 30 age- and gender-matcbed asymptomatic controls underwent a polysomnographic examination. Also, any self-reporting of daytime clenching (DC) was registered in 58 of these subjects. Results: Most MFP patients reported mild or moderate pain (46.67% and 43.33%, respectively), and only 3 (10%) reported severe pain. Pain duration ranged from 2 to 120 months (mean 34.67 +/- 36.96 months). Significant associations were observed between RMMA-SB and MFP as well as between DC and MFP. Conclusions: (1) RMMA-SB is significantly associated with MFP; (2) although RMMA-SB represents a risk factor for MFP, this risk is low; and (3) DC probably constitutes a stronger risk factor for MFP than RMMA-SB.

Increasing trends of sleep complaints in the city of São Paulo, Brazil

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Sleep, stress, neurocognitive profile and healthrelated quality of life in adolescents with idiopathic musculoskeletal pain

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)