Sleep and health: Everywhere and in both directions.
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Health Status↗
Biomedical subjects
Phyllis C Zee
Publications and source records attributed to Phyllis C Zee.
The brain's master circadian clock: implications and opportunities for therapy of sleep disorders.
The suprachiasmatic nuclei (SCN) residing in the anterior hypothalamus maintains a near-24-h rhythm of electrical activity, even in the absence of environmental cues. This circadian rhythm is generated by intrinsic molecular mechanisms in the neurons of the SCN; however, the circadian clock is modulated by a wide variety of influences, including glutamate and pituitary adenylate cyclase-activating peptide (PACAP) from the retinohypothalamic tract, melatonin from the pineal gland, and neuropeptide Y from the intergeniculate leaflet. By virtue of these and other inputs, the SCN responds to environmental cues such as light, social and physical activities. In turn, the SCN controls or influences a wide variety of physiologic and behavioral functions, including attention, endocrine cycles, body temperature, melatonin secretion, and the sleep-wake cycle. Regulation of the sleep-wake cycle by the SCN has important implications for development of therapies for sleep disorders, including those involving desynchronization of circadian rhythms and insomnia.
Antioxidants↗
Neurobiology of circadian rhythm sleep disorders.
To adapt to a 24-hour environment, nearly all organisms, from mammals to single-celled organisms, have developed endogenous mechanisms that generate nearly 24-hour (circadian) rhythms in physiology and behavior, the most notable being that of the daily cycles of sleep and wake. Disruption of these circadian rhythms is often accompanied by disorders of sleep and wakefulness. With the recent advances in the molecular biology that underlies the development and maintenance of these rhythms, the pathophysiology behind circadian rhythm sleep disorders is becoming better understood.
Circadian Rhythm↗
Circadian rhythm sleep disorders and phototherapy.
Circadian rhythm sleep disorders are characterized by a desynchronization between the timing of the intrinsic circadian clock and the extrinsic light-dark and social/activity cycles resulting in symptoms of excessive sleepiness and insomnia. This article explores the six recognized circadian rhythm sleep disorders: delayed sleep phase syndrome, advanced sleep phase syndrome, non-24-hour sleep-wake syndrome, irregular sleep-wake pattern, shift work sleep syndrome, and time zone change syndrome. Additionally discussed are the therapeutic roles of synchronizing agents, such as light and melatonin.
Humans↗
The pipeline of investigators for sleep research--a crisis!
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Biomedical Research↗
Sleep: a marker of physical and mental health in the elderly.
OBJECTIVE: The objective of this study was to determine the occurrence and recognition of common sleep-related problems and their relationship to health-related quality-of-life measures in the elderly. METHOD: A total of 1,503 participants with a mean age of 75.5 (+/- 6.8, range: 62-100) years from 11 primary care sites serving primarily elderly patients were interviewed. Subjects completed a five-item sleep questionnaire and the SF-12. A Physical Component Summary (PCS-12) and Mental Component Summary (MCS-12) score was calculated. A systematic medical chart review was conducted to determine whether sleep problems were identified by the healthcare providers. RESULTS: A total of 68.9% of patients reported at least one sleep complaint and 40% had two or more. Participants most commonly endorsed (45%) that they had "difficulty falling asleep, staying asleep, or being able to sleep." The number and type of sleep problems endorsed was associated with both physical and mental health quality-of-life status. Excessive daytime sleepiness was the best predictor of poor mental and physical health-related quality of life. Even when all five sleep questions were endorsed, a sleep complaint was only reported in the chart 19.2% of the time. CONCLUSIONS: When elicited, sleep complaints predicted the general physical and mental health-related quality-of-life status in elderly populations with comorbid medical and mental illnesses. Yet, questions regarding sleep are not an integral component of most clinical evaluations. Given the growing evidence of a relationship between sleep and health, identification of sleep disorders could lead to improved management of common age-related chronic illnesses and quality of life of elderly patients.
Aged↗
Circadian rhythm sleep disorders.
Humans exhibit endogenous circadian rhythms that are regulated by the master circadian clock of the body, the suprachiasmatic nucleus. These endogenous circadian rhythms are aligned to the outside world by social and environmental cues. Circadian rhythm sleep disorders (CRSD) occur when there is an alteration of the internal timing mechanism or a misalignment between sleep and the 24-h social and physical environment. CRSD are often underrecognized yet should be considered in the differential of patients presenting with symptoms of insomnia and/or hypersomnia. Because behavioral and environmental factors often are involved in the development and maintenance of these conditions, a multimodal treatment approach of behavioral and/or pharmacologic approaches is usually required to synchronize a patient's circadian rhythm to the 24-h environment, consolidate sleep, and improve alertness. Rapid advances in our understanding of the physiologic, cellular, and molecular basis of circadian rhythm and sleep regulation will likely lead to improved diagnostic tools and treatments for CRSD.
Circadian Rhythm↗
Phase-dependent treatment of delayed sleep phase syndrome with melatonin.
STUDY OBJECTIVE: Delayed sleep phase syndrome (DSPS) is a circadian-rhythm sleep disorder characterized by abnormally late sleep and wake times. Melatonin, taken in the evening, advances sleep and circadian phase in patients with DSPS. However, little is known about the most effective dose or time of administration. In the present study, we tested the effectiveness of melatonin to advance the timing of sleep and circadian phase in individuals with DSPS. DESIGN: Following baseline assessment of sleep and circadian phase, subjects were randomly assigned to 1 of 3 treatment groups. The administration of melatonin (0.3 or 3.0 mg) or placebo was double-blinded. SETTING: All procedures were conducted on an outpatient basis. PARTICIPANTS: Thirteen subjects with DSPS, recruited via flyers, advertisements, and referrals from the Sleep Clinic, completed this study. INTERVENTIONS: Melatonin (0.3 or 3.0 mg) or placebo was administered between 1.5 and 6.5 hours prior to dim light melatonin onset for a 4-week period. MEASUREMENTS AND RESULTS: Both doses of melatonin advanced the circadian phase of endogenous melatonin. The magnitude of phase advance in dim-light melatonin onset correlated strongly with the time of melatonin administration, with earlier times being more effective (r2 = 0.94, P < .0001). Similar, though weaker, relationships were obtained between the timing of melatonin administration and changes in sleep time. CONCLUSIONS: These results indicate that melatonin advances the circadian clock and sleep in patients with DSPS in a phase-dependent manner. This is the first study that reports a relationship between timing of melatonin administration and phase changes in patients with DSPS.
Adult↗
Cystic fibrosis patients have poor sleep quality despite normal sleep latency and efficiency.
STUDY OBJECTIVES: Cystic fibrosis (CF) patients may be predisposed to poor sleep quality due to upper and lower airway abnormalities and impaired gas exchange. Previous sleep investigations of CF patients using single-night polysomnography have reported conflicting results. We hypothesized that sampling sleep for a prolonged period in a patient's normal environment may give a more representative assessment of sleep quality than a single-night polysomnogram, and that impaired sleep quality would correlate with pulmonary disease severity and self-assessed sleep quality. DESIGN: Using wrist actigraphy, we measured sleep quality in clinically stable CF patients and age-matched control subjects. In addition, each CF patient and control subject completed the following three questionnaires: the Epworth sleepiness scale; the Pittsburgh sleep quality index (PSQI); and the Medical Outcomes Study 36-item short form. RESULTS: Twenty CF patients and control subjects were enrolled in the study, and were well-matched for age, sex, and body mass index. The mean (+/- SD) FEV(1) for CF patients was 61.0 +/- 20.1% predicted. CF patients and control subjects had similar sleep duration, sleep latency, and sleep efficiency. However, CF patients had higher PSQI scores (6.45 vs 4.55, respectively; p = .04), a higher fragmentation index (FI) [31.72 vs 18.02, respectively; p < 0.001], and less immobile time (88.87 vs 91.89, respectively; p = 0.02). There was a significant correlation of FI with FEV(1) and PSQI scores. CONCLUSIONS: Stable CF patients have disrupted sleep, and sleep disruption may in part be related to the severity of pulmonary disease. In addition, the PSQI may be useful in detecting CF patients with poor sleep quality.
Adult↗
The impact of school daily schedule on adolescent sleep.
OBJECTIVES: This study was initiated to examine the impact of starting school on adolescent sleep, to compare weekday and weekend sleep times, and to attempt to normalize the timing of the circadian sleep/wake cycle by administering bright light in the morning. This was a collaborative project involving high school students and their parents, as well as high school and university faculty members, for the purpose of contributing information to the scientific community while educating students about research processes and their own sleep/wake cycles and patterns. METHODS: Sixty incoming high school seniors kept sleep/wake diaries beginning in August and continuing through 2 weeks after the start of school in September. Sleep diaries were also kept for 1 month in November and 1 month in February. Early-morning light treatments were given to 19 students in the last 2 weeks of November and the last 2 weeks of February. Neuropsychologic performance was measured with computer-administered tests. Paper-and-pencil tests were used for assessment of mood and vigor. A testing period consisted of 2 consecutive days at the beginning and end of November and at the beginning and end of February. Tests were given 3 times per day, ie, in the morning before school (6:30-8:00 AM), during midday lunch periods (11:30 AM to 1:00 PM), and in the afternoon (3:00-4:30 PM), on each of the test days. RESULTS: Adolescents lost as much as 120 minutes of sleep per night during the week after the start of school, and weekend sleep time was also significantly longer (approximately 30 minutes) than that seen before the start of school (August). No significant differences were found between weekday sleep in the summer and weekend sleep during the school year. Early-morning light treatments did not modify total minutes of sleep per night, mood, or computer-administered vigilance test results. All students performed better in the afternoon than in the morning. Students in early morning classes reported being wearier, being less alert, and having to expend greater effort. CONCLUSIONS: The results of this study demonstrated that current high school start times contribute to sleep deprivation among adolescents. Consistent with a delay in circadian sleep phase, students performed better later in the day than in the early morning. However, exposure to bright light in the morning did not change the sleep/wake cycle or improve daytime performance during weekdays. Both short-term and long-term strategies that address the epidemic of sleep deprivation among adolescents will be necessary to improve health and maximize school performance.
Adolescent↗
Sleep promoting role of melatonin receptor agonists.
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Circadian Rhythm↗
Morning or evening activity improves neuropsychological performance and subjective sleep quality in older adults.
STUDY OBJECTIVES: Sleep disturbances and decline in neuropsychological performance are common in older adults. Reduced social and physical activity is likely a contributing factor for these age-related changes in sleep and cognition. We previously demonstrated that a program of structured social and physical activity, with 2 daily activity sessions, 1 in the morning and 1 in the evening for a relatively short period of 2 weeks, improved sleep and neuropsychological performance in community-dwelling older adults. The goals of this pilot study were to determine whether a single daily morning or evening activity session for 2 weeks would also improve sleep and neuropsychological function and whether these effects were dependent on the timing of the activity sessions. DESIGN: We compared the effect of morning or evening structured activity sessions in a repeated-measures crossover design. Subjective mood, neuropsychological performance tasks, and subjective and objective measures of sleep were assessed at baseline and after the intervention. SETTING: All procedures took place in the participant's residence. PARTICIPANTS: Twelve older men and women (74.6 +/- 5.5 years of age). INTERVENTIONS: Subjects participated in 14 days of structured activity sessions in the morning (9:00-10:30 am) or evening (7:00-8:30 pm). Sessions consisted of stretching, low-impact aerobics, and game playing. MEASUREMENTS AND RESULTS: Exposure to either morning or evening activity significantly improved performance on a neuropsychological test battery. Morning activity sessions increased throughput on 4 of 8 performance tasks, while evening activity sessions improved throughput on 7 of the 8 performance tasks. Subjective sleep-quality ratings, measured by the Pittsburg Sleep Quality Index, improved following activity sessions in either the morning or the evening. Objective measures of sleep did not improve when measured by actigraphy or polysomnography. CONCLUSIONS: These results suggest that short-term exposure to either morning or evening social and physical activity improves objective measures of neuropsychological performance and subjective sleep quality in the elderly. Increasing exposure to social and physical activity may be a useful intervention to improve sleep quality and daytime function in older adults.
Affect↗
Circadian rhythm sleep disorders.
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Body Temperature↗
Circadian rhythm disorders.
Circadian rhythm sleep disorders occur when individuals attempt to sleep at the wrong circadian time. The misalignment between the internal circadian timing system and the external environment is typically due to either an alteration in the functioning of the circadian timing system (e.g., delayed or advanced sleep phase syndrome) or to changes in the external environment (e.g., jet lag). However, the clinical presentation of most of the circadian rhythm sleep disorders is influenced by a combination of physiological, behavioral, and environmental factors. These disorders lead to complaints of insomnia and excessive daytime sleepiness, with impairment in important areas of functioning and quality of life. Current treatments primarily involve the use of circadian synchronizing agents, such as light, to realign the internal and external environment. These treatments are limited by the availability of adequate diagnostic tools and well-controlled clinical trials. A better understanding of the pathophysiology of these disorders is required to develop more effective treatments.
Humans↗
Factors influencing cognitive function, sleep, and quality of life in individuals with systemic lupus erythematosus: a review of the literature.
Cognitive dysfunction represents one of several neurological and psychiatric complications of Systemic Lupus Erythematosis (SLE). Additional manifestations of nervous system involvement subsumed under the term neuropsychiatric SLE (NPSLE) include cerebrovascular disorder, seizures, psychosis, acute confusional state, anxiety and mood disorders. Neuropsychological investigations have facilitated the identification and description of cognitive impairment in SLE and NPSLE. Salient findings from studies of SLE-related cognitive dysfunction are reviewed with respect to neuroimaging procedures, indices of disease activity, and potential moderator variables. Data on cognitive functioning are also discussed in reference to other disease aspects including fatigue, sleep disturbance, and impact on health-related quality of life (HRQL). To date, neuropsychological functioning has been studied extensively, albeit separately from other commonly reported SLE-related symptoms. Future research may profit from investigating relationships between cognitive impairment, sleep disturbance and fatigue and their collective impact on functional capacity and quality of life.
Cognition↗
Nimodipine potentiates light-induced phase shifts of circadian activity rhythms but not c-fos expression in the suprachiasmatic nucleus of mice.
The present study assessed whether treatment with the L-type calcium channel antagonist nimodipine affects the responsiveness of the circadian pacemaker to light in C3H/HeN mice. Nimodipine (10 mg/kg, sc) increased the magnitude of light-induced phase delays (P<0.01) and c-fos mRNA expression in the paraventricular nuclei (P<0.01), but not in the suprachiasmatic nuclei (SCN). These results suggest that nimodipine may affect phase shifts of circadian activity rhythms through a mechanism independent of c-fos expression in the SCN.
Animals↗
Circadian phase-shifting effects of nocturnal exercise in older compared with young adults.
Exercise can phase shift the circadian rhythms of young adults if performed at the right time of day. Similar research has not been done in older adults. This study examined the circadian phase-delaying effects of a single 3-h bout of low-intensity nocturnal exercise in older (n = 8; 55-73 yr old) vs. young (n = 8; 20-32 yr old) adults. The exercise occurred at the beginning of each subject's habitual sleep time, and subjects sat in a chair in dim light during the corresponding time in the control condition. The dim-light melatonin onset (DLMO) was used as the circadian phase marker. The DLMO phase delayed more after the exercise than after the control condition. On average, the difference in phase shift between the exercise and control conditions was similar for older and young subjects, demonstrating that the phase-shifting effects of exercise on the circadian system are preserved in older adults. Therefore, exercise may potentially be a useful treatment to help adjust circadian rhythms in older and young adults.
Adult↗