Circadian regulation of human sleep and age-related changes in its timing, consolidation and EEG characteristics.

The light-entrainable circadian pacemaker located in the suprachiasmatic nucleus of the hypothalamus regulates the timing and consolidation of sleep by generating a paradoxical rhythm of sleep propensity; the circadian drive for wakefulness peaks at the end of the day spent awake, ie close to the onset of melatonin secretion at 21.00-22.00 h and the circadian drive for sleep crests shortly before habitual waking-up time. With advancing age, ie after early adulthood, sleep consolidation declines, and time of awakening and the rhythms of body temperature, plasma melatonin and cortisol shift to an earlier clock hour. The variability of the phase relationship between the sleep-wake cycle and circadian rhythms increases, and in old age sleep is more susceptible to internal arousing stimuli associated with circadian misalignment. The propensity to awaken from sleep advances relative to the body temperature nadir in older people, a change that is opposite to the phase delay of awakening relative to internal circadian rhythms associated with morningness in young people. Age-related changes do not appear to be associated with a shortening of the circadian period or a reduction of the circadian drive for wake maintenance. These changes may be related to changes in the sleep process itself, such as reductions in slow-wave sleep and sleep spindles as well as a reduced strength of the circadian signal promoting sleep in the early morning hours. Putative mediators and modulators of circadian sleep regulation are discussed.     

Circadian phase resetting in older people by ocular bright light exposure.

BACKGROUND: Aging is associated with frequent complaints about earlier bedtimes and waketimes. These changes in sleep timing are associated with an earlier timing of multiple endogenous rhythms, including core body temperature (CBT) and plasma melatonin, driven by the circadian pacemaker. One possible cause of the age-related shift of endogenous circadian rhythms and the timing of sleep relative to clock time is a change in the phase-shifting capacity of the circadian pacemaker in response to the environmental light-dark cycle, the principal synchronizer of the human circadian system. METHODS: We studied the response of the circadian system of 24 older men and women and 23 young men to scheduled exposure to ocular bright light stimuli. Light stimuli were 5 hours in duration, administered for 3 consecutive days at an illuminance of approximately 10,000 lux. Light stimuli were scheduled 1.5 or 3.5 hours after the CBT nadir to induce shifts of endogenous circadian pacemaker to an earlier hour (phase advances) or were scheduled 1.5 hours before the CBT nadir to induce shifts to a later hour (phase delays). The rhythms of CBT and plasma melatonin assessed under constant conditions served as markers of circadian phase. RESULTS: Bright light stimuli elicited robust responses of the circadian timing system in older people; both phase advances and phase delays were induced. The magnitude of the phase delays did not differ significantly between older and younger individuals, but the phase advances were significantly attenuated in older people. CONCLUSIONS: The attenuated response to light stimuli that induce phase advances does not explain the advanced phase of the circadian pacemaker in older people. The maintained responsiveness of the circadian pacemaker to light implies that scheduled bright light exposure can be used to treat circadian phase disturbances in older people.     

Owls, larks and the significance of morningness/eveningness rhythm propensity in psychiatric-mental health nursing

In the last decade there has been an upsurge in the research focusing on the interplay between the human circadian timing system and behavioral patterns in health and illness. Of particular interest in this area of inquiry is the overlay of what has been termed chronotype. What this refers to is the propensity of biological rhythms to express themselves in certain patterns of behavior. Commonly, these patterns have received names such as owl (evening chronotype) or lark (morning chronotype). Many people are neither a strong morning nor evening chronotype. If illness represents a change in the way a person's body functions within a given environment, then it is reasonable to believe that an "owl's" symptom presentation may vary significantly from the patterns of a "lark" who becomes ill. Recognizing that psychiatric nurses at both the generalist and the advanced practice levels have a strong interest in patterns of behavior, it stands to reason that using a lens that incorporates notions of the body's clock becomes essential. The interplay between the body's timing system and the thousands of other psychobiological rhythmic functions occurring everyday and within every human being is referred to as chronobiology. This article provides a primer for psychiatric nurses on issues of chronobiology related to morningness and eveningness rhythm propensity.     

OWLS,LARKS AND THE SIGNIFICANCE OF MORNINGNESS/EVENINGNESS RHYTHM PROPENSITY IN PSYCHIATRIC-MENTAL HEALTH NURSING

In the last decade there has been an upsurge in the research focusing on the interplay between the human circadian timing system and behavioral patterns in health and illness. Of particular interest in this area of inquiry is the overlay of what has been termed chronotype. What this refers to is the propensity of biological rhythms to express themselves in certain patterns of behavior. Commonly, these patterns have received names such as owl (evening chronotype) or lark (morning chronotype). Many people are neither a strong morning nor evening chronotype. If illness represents a change in the way a person's body functions within a given environment, then it is reasonable to believe that an "owl's" symptom presentation may vary significantly from the patterns of a "lark" who becomes ill. Recognizing that psychiatric nurses at both the generalist and the advanced practice levels have a strong interest in patterns of behavior, it stands to reason that using a lens that incorporates notions of the body's clock becomes essential. The interplay between the body's timing system thousands of other psychobiological rhythmic occurring everyday and within every human being to as chronobiology. This article provides a primer a for psychiatric nurses on issues of chronobiology to morningness and eveningness rhythm propensity.     

Sleep and circadian schedule disorders

The timing and synchronization of human circadian rhythms is important for health and well-being. Some individuals, for reasons that remain unclear, display less resilience or flexibility in their ability to synchronize to the 24-hour world and are thus diagnosed with a circadian schedule disorder. The objective of this article is to briefly introduce concepts about human circadian timing and to review what is known about chronic, long-term circadian schedule disorders such as delayed sleep phase syndrome, advanced sleep phase syndrome, irregular sleep-wake patterns, and non-24-hour sleep-wake disorder. Practical considerations for the clinician caring for these individuals are discussed.     

Effects of phototherapy in neonates on circadian sleep-wake and saliva cortisol level rhythms

The influence of phototherapy treatment during the neonatal period on sleep-wake rhythm, and its long-term effects on biological rhythms, was evaluated in preterm and full-term infants. Forty-three infants treated with phototherapy during the neonatal period and 47 untreated infants were examined for entrainment of sleep-wake rhythms between 16 and 52 weeks and for sleep-wake and saliva cortisol rhythms at 2.5 years of age. The age of sleep-wake rhythm entrainment was not significantly different between the 2 groups. No correlations between duration of exposure to phototherapy and corrected age of entrainment of sleep-wake rhythm were observed. At follow-up, no significant differences in sleep-wake and saliva cortisol rhythms were observed between the 2 groups, indicating that circadian variations were similar to those in adults.     

Racial Differences in the Human Endogenous Circadian Period

The length of the endogenous period of the human circadian clock (tau) is slightly greater than 24 hours. There are individual differences in tau, which influence the phase angle of entrainment to the light/dark (LD) cycle, and in doing so contribute to morningness-eveningness. We have recently reported that tau measured in subjects living on an ultradian LD cycle averaged 24.2 hours, and is similar to tau measured using different experimental methods. Here we report racial differences in tau. Subjects lived on an ultradian LD cycle (1.5 hours sleep, 2.5 hours wake) for 3 days. Circadian phase assessments were conducted before and after the ultradian days to determine the change in circadian phase, which was attributed to tau. African American subjects had a significantly shorter tau than subjects of other races. We also tested for racial differences in our previous circadian phase advancing and phase delaying studies. In the phase advancing study, subjects underwent 4 days of a gradually advancing sleep schedule combined with a bright light pulse upon awakening each morning. In the phase delaying study, subjects underwent 4 days of a gradually delaying sleep schedule combined with evening light pulses before bedtime. African American subjects had larger phase advances and smaller phase delays, relative to Caucasian subjects. The racial differences in tau and circadian phase shifting have important implications for understanding normal phase differences between individuals, for developing solutions to the problems of jet lag and shift work, and for the diagnosis and treatment of circadian rhythm based sleep disorders such as advanced and delayed sleep phase disorder.     

The influence of bright light during the daytime upon circadian rhythm of core temperature and its implications for nocturnal sleep

Abstract The purpose of the present study was to investigate how bright light during the daytime could influence circadian rhythms of core temperature and nocturnal sleep. Seven females (age 20 ± 2 years) served as participants. The participants lived in the experimental unit for 4 days and were exposed to either 6000 lx (bright) or 200 lx (dim) light during the daytime. Rectal temperature (T_re) was measured during the experimental period. Subjective alertness was measured by the Kansei-gakuin Sleeping Scale five times a day. The minimum T_re was significantly lower after bright exposure ( P < 0.05). The T_re fell rapidly after bright exposure before they retired ( P < 0.05) and increased more rapidly during bright light after they woke up ( P < 0.05). The morning wakefulness under bright exposure was more active than under dim exposure ( P < 0.05). The melatonin secretion at wake up during bright exposure was significantly lower than during dim exposure ( P < 0.05). Exposure to bright light during daytime lowered the nocturnal level of T_re, its evening fall was faster and the morning rise quicker. This suggests that indoor light during daytime should be bright enough to promote healthy sleep at night.     

Sleep quality and morningness–eveningness of shift nurses

Aim and objective. The aim of the study was to analyse, while controlling for identified covariates, the effects of morningness–eveningness on sleep quality for shift nurses. Background. Shift nurses had greater difficulty falling asleep or staying asleep, thus resulting in higher rates of retiring from hospital. Existing research has addressed the effects of manpower demand and personal preferences on shift assignment; however, the concept of endogenous rhythms is rarely considered. Methods. This analysis included 137 nurses between the ages of 21–58. Nurses completed the Horne and Ostberg questionnaire to assess morningness‐eveningness and the Pittsburgh Sleep Quality Index (PSQI) questionnaire to measure self‐reported sleep quality over the last month. The 18‐point Chinese version had a Cronbach's reliability coefficient of 0·79 overall and 0·86 respectively. This study analysed correlates of sleep quality by comparing the groups with better or worse sleep quality according to the median of PSQI. Univariate and multivariate analyses were used for the risk factors of worse sleep quality. Results. The result showed that the strongest predictor of sleep quality was morningness–eveningness not the shift schedule or shift pattern for nurses under controlling the variable of age. Greater age and longer years employed in nursing significantly decreased the risk of worse sleep quality. The confounding age factor was properly controlled; evening types working on changing shifts had higher risk of poor sleep quality compared to morning types. Conclusions. Morningness–eveningness was the strongest predictor of sleep quality under controlling the variable of age in shift nurses. Implications for clinical practice. Our results suggested that determining if nurses were attributed to morning or evening types is an important sleep issue before deciding the shift assignment.     

Sleep quality, chronotypes and preferential timing of attacks in migraine without aura

Clinical observations show that migraine attacks have a seasonal, menstrual and circadian timing, suggesting a role of chronobiological mechanisms and their alterations in the disease, but little experimental data exists about this issue. The aim of this study was to estimate sleep quality chronotypes and the possible circadian timing of attacks in migraneurs. One hundred patients suffering from migraine without aura according to the IHS criteria (2004), and 30 controls were enrolled. Morning and evening type subjects were more represented in migraine patients than in controls and showed a tendency towards worse sleep quality and higher disability. Forty–two percent of migraineurs presented more than 75% of their attacks at night. Morning and evening types rather than intermediate and differences between real and preferred times may represent stressors that can worsen the disease. A preferential timing for occurrence of migraine attacks during the night and early morning hours was documented.     

Circadian rhythms, sleep, and metabolism

The discovery of the genetic basis for circadian rhythms has expanded our knowledge of the temporal organization of behavior and physiology. The observations that the circadian gene network is present in most living organisms from eubacteria to humans, that most cells and tissues express autonomous clocks, and that disruption of clock genes results in metabolic dysregulation have revealed interactions between metabolism and circadian rhythms at neural, molecular, and cellular levels. A major challenge remains in understanding the interplay between brain and peripheral clocks and in determining how these interactions promote energy homeostasis across the sleep-wake cycle. In this Review, we evaluate how investigation of molecular timing may create new opportunities to understand and develop therapies for obesity and diabetes.     

Reducing disruption of circadian temperature rhythm following surgery

Temperature and other circadian rhythms are disrupted following surgery and other traumatic events. During recovery, coordination between temperature rhythms and other rhythmic physiologic processes is reduced. Studies of animals and humans have shown that return of synchrony is not immediate, but that it is important in the recovery process. The purpose of this study was to test a combination of cues that have been shown to adjust the timing of circadian temperature rhythm. The combined cues consisted of timed ingestion of caffeine and protein foods and adjustment of the sleep/wake cycle. The intervention was tested in 26 age- and gender-matched maxillofacial surgery patients. Patients were randomly assigned to control or experimental groups. Circadian temperature rhythm was measured by continuous monitoring with axillary probes and miniature recorders before and after surgery. Following surgery, both experimental and control subjects displayed 24-hour circadian temperature rhythms; however, the peak-to-trough difference was decreased more following surgery in the control subjects than in the subjects who had prepared for surgery by practicing the intervention. Control subjects also had less day-to-day stability in the phase of their rhythms following surgery. These results suggest that the intervention reduced circadian disruption following surgery and provides a way for patients to prepare themselves to resist rhythm changes.     

Neurophysiology of swallowing: Effects of age and bolus type

This study examined age-related changes in swallowing from an integrated biomechanical and functional imaging perspective in order to more comprehensively characterize changes in swallowing associated with age. We examined swallowing-related fMRI brain activity and videoflouroscopic biomechanics of three bolus types (saliva, water and barium) in 12 young and 11 older adults. We found that age-related neurophysiological changes in swallowing are evident. The group of older adults recruited more cortical regions than young adults, including the pericentral gyri and inferior frontal gyrus pars opercularis and pars triangularis (primarily right-sided). Saliva swallows elicited significantly higher BOLD responses in regions important for swallowing compared to water and barium. In separate videofluoroscopy sessions, we obtained durational measures of supine swallowing. The older cohort had significantly longer delays before the onset of the pharyngeal swallow response and increased residue of ingested material in the pharynx. These findings suggest that older adults without neurological insult elicit more cortical involvement to complete the same swallowing tasks as younger adults.     

Gastrointestinal chronopharmacology: physiology, pharmacology and therapeutic implications.

This chapter discusses the influence of ultradian and circadian rhythms of gastrointestinal motor and secretory function on the action of orally administered drugs. Most drugs exhibit more rapid absorption in the morning compared to the evening due, in part, the circadian alterations in gastric emptying. Gastric acid secretion and gastrointestinal toxicity to oral drugs also display circadian rhythmicity. These observations provide a rationale for use or avoidance of drugs based on time-of-day dosing considerations. The chronopharmacological behavior of a drug may thus play an important role in the effectiveness of any oral medication treatment schedule.     

Diagnosis and treatment in circadian rhythm sleep disorders

Circadian rhythm sleep disorders (CRSD) are characterized by misalignment between major sleep episode and desired sleep phase, or symptoms associated with internal desynchronization between endogenous circadian rhythm and overt sleep-wake rhythm. Endogenous circadian rhythm is mainly regulated by master circadian clock located in the suprachiasmatic nucleus. Light entrains the circadian clock according to a phase-response curve. Furthermore, social time cue affects human sleep-wake rhythm. Instructions concerning sleep hygiene including light environment play fundamental role for the treatment in CRSD. In addition, light therapy and oral melatonin administration have application to delayed sleep phase type. Diagnostic classification and treatment in each types of CRSD are reviewed in this article.     

Circadian variability at oral, tympanic and axillary temperature in hospitalized adults

The aim of this study was to measure the circadian variability of patients' temperature in the eardrum, oral, and armpit positions considering the measurement angle. The study was carried out at the State University of Campinas' Clinics Hospital (HC Unicamp), a school hospital in the city of Campinas, State of S?o Paulo. Temperatures were taken in the Cardiology, Adult General Clinic and Gastric infirmaries every two hours in two consecutive days, from the time patients woke up until 10 PM. The results show a significant difference, p-value = 0.0001, between the morning and afternoon periods compared to the evening period. The Tukey test has also showed a difference. It was observed that the measurement in the eardrum position resulted in higher temperatures compared to the other positions, thus confirming data in the international literature. The circadian variability eardrum temperature was similar to the measurements of the oral temperature during the patients' awaked period.     

Human circadian variations

Circadian rhythms, present in most phyla across life, are biological oscillations occurring on a daily cycle. Since the discovery of their molecular foundations in model organisms, many inputs that modify this tightly controlled system in humans have been identified. Polygenic variations and environmental factors influence each person’s circadian rhythm, contributing to the trait known as chronotype, which manifests as the degree of morning or evening preference in an individual. Despite normal variation in chronotype, much of society operates on a “one size fits all” schedule that can be difficult to adjust to, especially for certain individuals whose endogenous circadian phase is extremely advanced or delayed. This is a public health concern, as phase misalignment in humans is associated with a number of adverse health outcomes. Additionally, modern technology (such as electric lights and computer, tablet, and phone screens that emit blue light) and lifestyles (such as shift or irregular work schedules) are disrupting circadian consistency in an increasing number of people. Though medical and lifestyle interventions can alleviate some of these issues, growing research on endogenous circadian variability and sensitivity suggests that broader social changes may be necessary to minimize the impact of circadian misalignment on health.     

Crosstalk between central and peripheral biological clocks

Mammalian circadian system is multi-oscillator system. Clock gene expression analysis revealed that central clock, suprachiasmatic nucleus, organizes and synchronizes the peripheral oscillators in the whole body cells. Similarly, human circadian system is considered to be dual oscillation system because of internal desynchronization between melatonin, body temperature rhythms(driven by oscillator I) and sleep-wake rhythm (driven by oscillator II) under temporal isolation of dim light conditions. These oscillators control their periods mutually which means there is crosstalk of oscillators. Although the effect from oscillator II to oscillator I is weak under experimental dim light conditions, sleep-wake behavior controls light input to light sensitive oscillator I and feedbacks to sleep-wake driving oscillator II under lighting condition we live. To understand these mechanisms is important for prevention of circadian rhythm related diseases.     

The impact of delirium on the circadian distribution of breakthrough analgesia in advanced cancer patients

Most cancer patients will experience pain requiring opioid therapy during their illness. Standard opioid therapy includes fixed scheduled doses and so-called "rescue" doses for breakthrough pain. Circadian rhythms seem to influence the expression of pain and the responsiveness to analgesic medication. Delirium is a common complication in advanced cancer patients and it also may modify the expression of pain and the use of analgesic medication. We reviewed the circadian distribution of breakthrough analgesia (BTA) doses in 104 advanced cancer patients who were part of a prospective study of the occurrence of delirium. We found that the circadian distribution of BTA is significantly different from a random distribution in the case of patients with and without delirium. Patients without delirium tended to use more BTA (P < 0.001) in the morning, whereas patients with delirium tended to use more BTA in the evening and at night (P = 0.02). We conclude that delirium is associated with changes in the circadian distribution of BTA, which is possibly related to reversal of the normal circadian rhythm.     

Circadian,day-of-week,and age patterns of the occurrence of acute coronary syndrome in Beijing's emergency medical services system

Background

Previous in-hospital studies suggest that there are significant circadian rhythms associated with the incidence of acute coronary syndromes (ACSs). No study to date has examined the presentation of ACS in the prehospital setting. Our goal was to examine circadian, day-of-week, and age patterns of occurrence in ACS in a large, urban emergency medical services (EMS) system.

Methods

We retrospectively reviewed the electronic prehospital medical records from the Beijing's EMS system spanning August 1, 2005, to July 31, 2007. Data were analyzed by hour of the day and day of the week. χ² tests were performed to compare the difference.

Results

Seven thousand thirty-two cases of ACS were identified by the EMS system physicians during the 2-year study period, including 536 cases of acute myocardial infarction. A significant variation of circadian distribution of ACS was observed in both 24-hour (P < .001) and 2-hour (P < .001) interval time course. Two peaks were observed in the morning from 0800 to 1000 and approaching midnight from 2200 to 2400. Increases of 50% and 60.8% in the morning and evening peaks were found, respectively, when compared with the early morning baseline (nadir). No significant difference was found among the accumulated cases in 2 years on each day in a week (P = .203).

Conclusions

Our study shows that, in the Beijing metropolitan area, the presentation of ACS has significant circadian rhythm characterized by 2 peaks within 24 hours, the morning peak is 0800 to 1000, and the late evening peak is 2200 to 2400. No significant weekly rhythm was observed in the present study.