Circadian patterns of sleep, sleepiness, and performance in older and younger adults

STUDY OBJECTIVE: To compare circadian patterns of sleep, subjective sleepiness, and psychomotor performance in older and younger adults. DESIGN: Controlled experimental laboratory study. SETTING: General Clinical Research Center. PARTICIPANTS: Healthy older adults (n = 17, mean age 76 years) and healthy younger adults (n = 19, mean age 23 years). INTERVENTIONS: Subjects lived for 60 consecutive hours on a 90-minute sleep-wake cycle (30 minutes in bed, 60 minutes awake). Electroencephalographic recordings were conducted during bedrest periods. Self-ratings and psychomotor performance tests were conducted during 60-minute wake periods. MEASUREMENTS AND RESULTS: Data were analyzed with cosinor and linear mixed models. Amplitude and phase of the core body temperature rhythm did not significantly differ by age group. Older adults had significantly reduced mean levels and amplitude of rhythms in total sleep time and sleep efficiency and increased mean levels and amplitude of rhythms in sleep latency and wake after sleep onset. Age groups did not differ in mean level of subjective sleepiness, but older adults had reduced amplitude. Older adults had worse overall psychomotor performance, with evidence of larger circadian amplitude in some of these rhythms. Age groups did not differ on the phase position of any rhythm. CONCLUSIONS: Older adults had a lower level and smaller circadian variation of sleep propensity compared with younger adults, whereas wakefulness and psychomotor performance rhythms tended to show increased circadian variation among older subjects. These findings likely result from a combination of age-related changes in cortical function, homeostatic sleep mechanisms, and circadian regulation.     

Rat circadian rhythms entrain to a descending saw-tooth light intensity cycle.

We reexamined whether rat circadian rhythms entrained to the light intensity cycle of a descending saw-tooth (ST-d) form, in which illuminance decreased rectilinearly from 300 lx to 0 lx in 24 h, and abruptly returned to 300 lx (lights-on time). Ambulation, drinking and subcutaneous body temperature were simultaneously monitored in 5 intact, 5 pinealectomized and 5 orchiectomized rats. Additionally, sleep was monitored in the intact rats. In all the rats, entrainment was confirmed during 65 days' exposure to the ST-d cycle. The waveforms of the entrained rhythms were much modified compared with those during LD 12:12. The estimated activity periods of the entrained rhythms straddled the lights-on time of the ST-d cycle. In all the groups of rats, administration of a single ST-d cycle in constant dim red light produced only delay shifts irrespective of its circadian phase, and there was no significant circadian variation in the magnitude of phase shifts. The results indicate that rat circadian rhythms entrain to the ST-d cycle with an unexpected phase position, which cannot be explained by the phase-response curve.     

Objective measures of sleep and dim light melatonin onset in adolescents and young adults with delayed sleep phase disorder compared to healthy controls

Delayed sleep phase disorder is characterized by a delay in the timing of the major sleep period relative to conventional norms. The sleep period itself has traditionally been described as normal. Nevertheless, it is possible that sleep regulatory mechanism disturbances associated with the disorder may affect sleep duration and/or architecture. Polysomnographic data that may shed light on the issue are scarce. Hence, the aim of this study was to examine polysomnographic measures of sleep in adolescents and young adults with delayed sleep phase disorder, and to compare findings to that of healthy controls. A second aim was to estimate dim light melatonin onset as a marker of circadian rhythm and to investigate the phase angle relationship (time interval) between dim light melatonin onset and the sleep period. Data from 54 adolescents and young adults were analysed, 35 diagnosed with delayed sleep phase disorder and 19 healthy controls. Results show delayed timing of sleep in participants with delayed sleep phase disorder, but once sleep was initiated no group differences in sleep parameters were observed. Dim light melatonin onset was delayed in participants with delayed sleep phase disorder, but no difference in phase angle was observed between the groups. In conclusion, both sleep and dim light melatonin onset were delayed in participants with delayed sleep phase disorder. The sleep period appeared to occur at the same circadian phase in both groups, and once sleep was initiated no differences in sleep parameters were observed.     

电刺激对军人血浆褪黑激素昼夜节律的影响

人体的生理与行为节律是由内源性昼夜节律钟产生与调控的。我们通过监测人体体核温度 ,就电针与光照肌对军人血浆褪黑激素节律的影响进行了研究 ,以探索电针调节人体节律的相位反应规律。实验结果显示 ,电针对军人血浆中的褪黑激素节律相位的影响具有明显的依时相性 ,其相位反应曲线呈光性模式。这一发现为治疗睡眠与节律混乱性疾病提供了新的思路。     

Poor compensatory function for sleep loss as a pathogenic factor in patients with delayed sleep phase syndrome

OBJECTIVE: Delayed sleep phase syndrome (DSPS) is a condition in which the patient is unable to reset or phase-advance his/her sleep timing properly after transient sleep delay and consequently shows persistent sleep phase delay. Prior studies suggested that DSPS is associated with a phase delay in the circadian pacemaker, but there was no evidence to explain the patient's inability to reset sleep phase. SUBJECTS AND METHODS: We used an ultra-short sleep-wake schedule together with simultaneous measurement of dim light melatonin rhythm after 24-hour sleep deprivation to allow the differential observation of diurnal sleep propensity fluctuation both from circadian and homeostatic aspects in 11 patients with DSPS (17-37 years; 8 men, 3 women) and 15 healthy controls (19-32 years; 8 men, 7 women). SETTING: NA. PATIENTS OR PARTICIPANTS: NA. INTERVENTIONS: NA. RESULTS: DSPS patients showed less ability to compensate for previous sleep loss during their circadian day and first hours of their circadian nighttime determined by dim light melatonin onset compared with controls, while controls compensated for previous sleep loss at most circadian times. Though shapes of dim light melatonin rhythm did not differ between the groups, phase angle between melatonin and sleep propensity rhythms was wider in DSPS patients than in controls. CONCLUSIONS: These findings suggest that poor compensatory function for sleep loss predisposes DSPS patients to failure to reset their sleep phase. Our results provide implications for understanding not only the pathophysiology of DSPS but also the biological basis for why some people can change their sleep schedule easily according to personal or social demands while others cannot.     

Advancing circadian rhythms before eastward flight: a strategy to prevent or reduce jet lag

STUDY OBJECTIVES: To develop a practical pre-eastward flight treatment to advance circadian rhythms as much as possible but not misalign them with sleep. DESIGN: One group had their sleep schedule advanced by 1 hour per day and another by 2 hours per day. SETTING: Baseline at home, treatment in lab. PARTICIPANTS: Young healthy adults (11 men, 15 women) between the ages of 22 and 36 years. INTERVENTIONS: Three days of a gradually advancing sleep schedule (1 or 2 hours per day) plus intermittent morning bright light (one-half hour approximately 5000 lux, one-half hour of <60 lux) for 3.5 hours. MEASUREMENTS AND RESULTS: The dim light melatonin onset was assessed before and after the 3-day treatment. Subjects completed daily sleep logs and symptom questionnaires and wore wrist activity monitors. The dim light melatonin onset advanced more in the 2-hours-per-day group than in the 1-hour-per-day group (median phase advances of 1.9 and 1.4 hours), but the difference between the means (1.8 and 1.5 hours) was not statistically significant. By the third treatment day, circadian rhythms were misaligned relative to the sleep schedule, and subjects had difficulty falling asleep in the 2-hours-per-day group, but this was not the case in the 1-hour-per-day group. Nevertheless, the 2-hours-per-day group did slightly better on the symptom questionnaires. In general, sleep disturbance and other side effects were small. CONCLUSIONS: A gradually advancing sleep schedule with intermittent morning bright light can be used to advance circadian rhythms before eastward flight and, thus, theoretically, prevent or reduce subsequent jet lag. Given the morning light treatment used here, advancing the sleep schedule 2 hours per day is not better than advancing it 1 hour per day because it was too fast for the advance in circadian rhythms. A diagram is provided to help the traveler plan a preflight schedule.     

Phase-shifting effects of bright morning light as treatment for delayed sleep phase syndrome

Bright light has recently been shown to have phase-shifting effects on human circadian rhythms. In this study we applied this effect to 20 patients with delayed sleep phase syndrome (DSPS) who were unable to fall asleep at conventional clock times and had a problem staying alert in the morning. In a controlled treatment study, we found that 2 h of bright light exposure in the morning together with light restriction in the evening successfully phase advanced circadian rhythms of core body temperature and multiple sleep latencies in these patients. This finding corroborates the importance of light for entraining human circadian rhythms.     

The treatment of early-morning awakening insomnia with 2 evenings of bright light

STUDY OBJECTIVE: To assess the effectiveness of brief bright-light therapy for the treatment of early-morning awakening insomnia. PARTICIPANTS: Twenty-four healthy adults with early-morning awakening insomnia were assigned to either the bright-light condition (2,500-lux white light) or the control (dim red light) condition. MEASUREMENTS AND RESULTS: The circadian phase of rectal temperature and urinary melatonin rhythms were assessed with 26-hour constant routines before and after 2 evenings of light therapy. Sleep and daytime functioning were monitored using sleep diaries, activity monitors, and mood scales before light therapy and for 4 weeks during the follow-up period. While there were no significant circadian phase changes in the dim-light control group, the bright-light group had significant 2-hour phase delays of circadian temperature and melatonin rhythm. Compared to pretreatment measures, over the 4-week follow-up period, the bright-light group had a greater reduction of time awake after sleep onset, showed a trend toward waking later, and had a greater increase of total sleep time. Participants in the bright-light condition also tended to report greater reductions of negative daytime symptoms, including significantly fewer days of feeling depressed at the 4-week follow-up, as compared with the control group. CONCLUSION: Two evenings of bright-light exposure phase delayed the circadian rhythms of early-morning awakening insomniacs. It also improved diary and actigraphy sleep measures and improved some indexes of daytime functioning for up to 1 month after light exposure. The study suggests that a brief course of evening bright-light therapy can be an effective treatment for early-morning awakening insomniacs who have relatively phase advanced circadian rhythms.     

Sleep structure in blindness is influenced by circadian desynchrony

We examined the structure, duration and quality of sleep, including non‐rapid eye movement sleep and rapid eye movement sleep, in 11 blind individuals without conscious light perception and 11 age‐ and sex‐matched sighted controls. Because blindness is associated with a greater incidence of free‐running circadian rhythms, we controlled for circadian phase by a measure of melatonin onset timing. When circadian rhythm was entrained and melatonin onset occurred at normal times, sleep structure did not differ between blind and sighted individuals. On the other hand, an abnormal timing of the circadian phase, including delayed, shifted and unclassifiable melatonin onsets, led to larger rapid eye movement sleep latencies and increased wake times. No differences were observed for stages of non‐rapid eye movement sleep, either between congenital and late blind and sighted individuals, or across the different circadian phases. Moreover, abnormal circadian phases were more common in the blind (n = 5) than the sighted (n = 2) sample. Our findings suggest that the sleep structure of blind individuals depends on entrainment of circadian phase, rather than on the absence of vision.     

Effect of running wheel availability on circadian patterns of sleep and wakefulness in mice

Sleep/wake expression in mice varies predictably with circadian phase. Such circadian rhythms are known to depend on intact suprachiasmatic nuclei (SCN) in the hypothalamus, but the mechanism by which SCN activity modulates sleep/wake expression is unknown. This paper examines the possibility that circadian patterns of sleep/wake derive partly from circadian timing of waking behaviors that are incompatible with sleep, such as locomotor activity. Voluntary locomotor activity was restricted in five mice adapted to a running wheel by locking the wheel in place. Continuous electrographic monitoring of sleep and wakefulness over multiple circadian cycles revealed: (1) during the active phase, shorter wake bouts and more frequent bouts of sleep, resulting in greater sleep/wake fragmentation and more time spent asleep; (2) during the rest phase, a small compensatory reduction in NREM sleep; (3) reduced amplitude of circadian sleep/wake rhythms and a greater amount of sleep overall. Thus, voluntary locomotor activity has an important influence on sleep/wake expression in mice, and the normal circadian pattern of sleep/wake depends on circadian timing of activity. Previous reports of damped circadian sleep/wake rhythms in rodents may therefore be explained by coincident diminutions in locomotor activity associated with age or health status. Our results also support analogous findings in human subjects, and we propose that elderly humans may benefit from therapies that augment daytime activity.     

Circadian control of thermoregulation in the squirrel monkey, Saimiri sciureus.

The characteristics and control of the circadian rhythms of core body temperature (colonic) and skin temperature (tail) were studied in chair-acclimatized squirrel monkeys (Saimiri sciureus). When animals were entrained to a light-dark cycle (12 h 600 lx; 12 h less than 1 lx) these two temperatures displayed prominent, reproducible, tightly coupled circadian rhythms. In contsant light of 600 lx, where no other effective circadian time cues were present, both temperature rhythms persisted with free-running periods. Within each animal, however, these rhythms were not as tightly coupled to one another as in LD. On occasion colonic and tail temperature rhythms free-ran with different circadian periods and some animals demonstrated "splitting" of the colonic temperature rhythm, with the colonic temperature rhythm displaying a bimodal pattern. These results suggest that the circadian rhythm of body temperature in primates is under the control of more than one potentially independent circadian oscillator.     

Responsiveness of the aging circadian clock to light

The present study assessed whether advances in sleep times and circadian phase in older adults might be due to decreased responsiveness of the aging circadian clock to light. Sixteen young (29.3 ± 5.6 years) and 14 older adults (67.1 ± 7.4 years) were exposed to 4 h of control dim (10 lux) or bright light (3500 lux) during the night. Phase shifts of the melatonin rhythm were assessed from the nights before and after the light exposure. Bright light delayed the melatonin midpoint in both young and older adults (p < 0.001). Phase delays for the older subjects were not significantly different from those of the young subjects for either the bright or dim light conditions. The magnitude of phase delays was correlated with both sleep offset and phase angle in the older, but not the younger subjects. The present results indicate that at light intensities commonly used in research as well as clinical practice older adults are able to phase delay to the same extent as younger subjects.     

Transient circadian internal desynchronization after light-dark phase shift in monkeys.

In four conscious chair-acclimatized squirrel monkeys (Saimiri sciureus) studied with lights on (600 lx) from 0800 to 2000 h daily (LD 12:12), prominent 24-h rhythms in feeding, drinking, activity, body temperature, and urinary potassium, sodium, and water excretion were seen. When the monkeys were subjected to 36 h of darkness followed by 36 h of light each variable demonstrated a circadian rhythm which was not passively dependent on the light-dark cycle. After the 24-h light-dark cycle was abruptly phase-delayed by 8 h, all the rhythms resynchronized with the new light-dark cycle phase, demonstrating that light-dark cycles are an effective zeitgeber. However, the resynchronization of the rhythms of feeding, drinking, activity, and body temperature was 90% complete within approximately 2 days while the 90% resynchronization of the urinary rhythms took approximately 5 days. These results suggest that the circadian timing system in S. sciureus may consist of several spontaneously oscillating units which can become transiently uncoupled during pertubations of environmental time cues.     

Short nights reduce light-induced circadian phase delays in humans

STUDY OBJECTIVE: Short sleep episodes are common in modern society. We recently demonstrated that short nights reduce phase advances to light. Here we show that short nights also reduce phase delays to light. DESIGN: Two weeks of 6-hour sleep episodes in the dark (short nights) and 2 weeks of long 9-hour sleep episodes (long nights) in counterbalanced order, separated by 7 days. Following each series of nights, there was a dim-light phase assessment to assess baseline phase. Three days later, subjects were exposed to a phase-delaying light stimulus for 2 days, followed by a final phase assessment. SETTING: Subjects slept at home in dark bedrooms but came to the laboratory for the phase assessments and light stimulus. PARTICIPANTS: Seven young healthy subjects. INTERVENTIONS: The 3.5-hour light stimulus was four 30-minute pulses of bright light (-5000 lux) separated by 30-minute intervals of room light. The stimulus began 2.5 hours after each subject's dim-light melatonin onset, followed by a 6- or 9-hour sleep episode. On the second night, the bright light and sleep episode began 1 hour later. MEASUREMENTS AND RESULTS: The dim-light melatonin onset and dimlight melatonin offset phase delayed 1.4 and 0.7 hours less in the short nights, respectively (both p < or = .015). CONCLUSIONS: These results indicate for the first time that short nights can reduce circadian phase delays, that long nights can increase phase delays to light, or both. People who curtail their sleep may inadvertently reduce their circadian responsiveness to evening light.     

Age-related changes in the circadian modulation of sleep-spindle frequency during nap sleep

STUDY OBJECTIVES: Sleep spindles exhibit a clear circadian modulation in healthy younger people. During the biological night (when melatonin is secreted), spindle density and spindle amplitude are high and spindle frequency and its variability are low, as compared with the biological day. We investigated whether this circadian modulation of spindle characteristics changes with age. DESIGN: A 40-hour multiple-nap paradigm under constant-routine conditions SETTING: Chronobiology Laboratory, University Psychiatric Hospitals, Basel, Switzerland PARTICIPANTS: Seventeen younger (20-31 years) and 15 older (57-74 years) volunteers. INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: Whereas the circadian modulation of spindle density, amplitude, duration, and intraspindle frequency variability was not greatly affected by age, we found significant changes in the circadian modulation of spindle frequency. The pronounced circadian modulation of spindle frequency in younger, but not older, subjects was phase locked with the circadian rhythm in melatonin secretion. In the latter, circadian modulation was attenuated and tended to be advanced with respect to the timing of melatonin secretion. There was no difference between age groups in the phase of the sleep-wake cycle or that of melatonin, nor did the phase angle between them differ. Although changes in the circadian modulation of spindle frequency in older subjects were accompanied by reduced amplitude in the sleep consolidation profile, there was no significant correlation between spindle frequency and sleep consolidation. CONCLUSION: This multiple-nap protocol under constant-routine conditions revealed an age-dependent weaker coupling of the circadian rhythms of spindle frequency and sleep propensity to the circadian rhythm of melatonin secretion.     

Sleep disturbance as transdiagnostic: Consideration of neurobiological mechanisms

Sleep disturbance is increasingly recognized as an important, but understudied, mechanism in the complex and multi-factorial causation of the symptoms and functional disability associated with psychiatric disorders. This review proposes that it is biologically plausible for sleep disturbance to be mechanistically transdiagnostic. More specifically, we propose that sleep disturbance is aetiologically linked to various forms of psychopathology through: its reciprocal relationship with emotion regulation and its shared/interacting neurobiological substrates in (a) genetics — genes known to be important in the generation and regulation of circadian rhythms have been linked to a range of disorders and (b) dopaminergic and serotonergic function — we review evidence for the interplay between these systems and sleep/circadian biology. The clinical implications include potentially powerful and inexpensive interventions including interventions targeting light exposure, dark exposure, the regulation of social rhythms and the reduction of anxiety. We also consider the possibility of developing a ‘transdiagnostic’ treatment; one treatment that would reduce sleep disturbance across psychiatric disorders.     

Convergence of circadian and sleep regulatory mechanisms on hypocretin-1

Hypocretin is a potential regulator of sleep and wakefulness and its levels fluctuate with the day-night cycle with high levels during the animal's activity period. Whether the daily fluctuations are driven endogenously or by external light cycles is unknown. We investigated the circadian and homeostatic regulation of hypocretin in the absence of environmental light cycles. To this purpose we performed repetitive samplings of cerebrospinal fluid in rats through implanted microcannulas in the cisterna magna and determined hypocretin-1 levels by radioimmunoassay. These experiments were also performed in rats that received a lesion of the suprachiasmatic nucleus (SCN), a major pacemaker for circadian rhythms in mammals. The results showed sustained rhythmicity of hypocretin in constant dim red light in control animals. SCN-lesioned animals showed no circadian rhythms in hypocretin and mean hypocretin levels were remarkably low. The results indicate that the SCN is indispensable for rhythmicity in hypocretin and induces a daily increase in hypocretin levels during the animal's active phase. Additional sleep deprivation experiments were carried out to investigate homeostatic regulation of hypocretin. Hypocretin levels increased in response to sleep deprivation in both control and SCN-lesioned animals, demonstrating that sleep homeostatic control of hypocretin occurs independently from the SCN. Our data indicate that the circadian pacemaker of the SCN and sleep homeostatic mechanisms converge on one single sleep regulatory substance.     

Various patterns of disrupted daily rest–activity rhythmicity associated with diabetes

Disruptions to sleep and circadian rhythms have now been recognized as common comorbidities in patients with medical illnesses. We aimed to determine if the diurnal rhythms for rest and activity were disrupted in parallel with the development of diabetic complications. Ninety outpatients in our diabetes clinic who had a body mass index <25 kg m² wore an actigraph for 7 consecutive days (42 men; mean age 68.7 ± 8.2 years). Patients with neuropsychiatric diseases, liver cirrhosis, renal failure, chronic obstructive pulmonary disease or blindness, or those who performed shiftwork were excluded. We grouped the actigraph recordings into 1‐h periods and counted the number of minutes that showed activity. Stepwise regression analysis showed an association between a diabetic clinical background and measurements of circadian rhythms such as daytime activity, night‐time activity, phase, interdaily stability, intradaily variability and relative amplitude. Higher age, body mass index, total cholesterol levels and insulin usage were associated with lower daytime activity and higher intradaily variability, whereas higher haemoglobin A1c levels and the presence of neuropathy were associated with greater daytime activity. The presence of proliferative retinopathy and increased levels of microalbuminuria were associated with higher intradaily variability and lower interdaily stability and amplitude. The presence of cardiovascular disease was associated with advanced phase, whereas painful neuropathy was associated with delayed phase. Our study demonstrated that different diabetic complications were associated independently with a variety of alterations in the circadian rest and activity rhythms. Our findings have provided novel insights that may be helpful in developing interventions for sleep–wake disorders associated with diabetes.     

Effects of light intensity on the circadian temperature and feeding rhythms in the squirrel monkey

The circadian rhythms of body temperature and feeding appear to be timed by separate pacemakers. Tonic administration of light has been used to investigate the response of the pacemaker timing behavioral rhythms; however, the response of the body temperature rhythm has not been similarly examined. This study investigates the circadian timing of the body temperature rhythm under conditions of different light intensity. We simultaneously recorded the patterns of both feeding and body temperature in squirrel monkeys free-running in an environment free of external time cues. In each lighting condition, the periods of the body temperature and feeding rhythms were identical. In constant bright light the rhythm periods were longer than when the animals were exposed to constant dim light. In addition, the variability of the periods was dependent on light intensity. The feeding rhythm period variance of animals in constant bright light was smaller than when in dim light. Conversely, the period of the free-running body temperature rhythm exhibited more variability in bright light than in dim light. Further, in each condition, there were changes in phase angle relationship between feeding and body temperature which were qualitatively similar to those observed in humans, although quantitatively smaller in magnitude. Thus, in the squirrel monkey, tonic light studies reveal that the mean circadian period of the body temperature and feeding rhythms are similar. However, changes in phase relationship, and differential rhythm period stabilities suggest differences in the period of the underlying, tightly coupled pacemakers.