Twelve-Hour Night Shifts of Healthcare Workers: A Risk to the Patients?

We assessed the impact of 12h fixed night shift (19:00–07:00h) work, followed by 36h of off-time, on the sleep–wake cycle, sleep duration, self-perceived sleep quality, and work-time alertness on a group composed of 5 registered and 15 practical nurses. Wrist actigraphy (Ambulatory Monitoring, Inc.), with data analysis by the Cole-Kripke algorithm, was applied to determine sleep/wake episodes and their duration. The sleep episodes were divided into six categories: sleep during the night shift (x¯=208.6; SD±90.6mins), sleep after the night shift (x¯=138.7; SD±79.6min), sleep during the first night after the night work (x¯=318.5; SD±134.6min), sleep before the night work (x¯=104.3; SD±44.1min), diurnal sleep during the rest day (x¯=70.5; SD±43.0min), and nocturnal sleep during the rest day (x¯=310.4; SD±188.9mins). A significant difference (p<.0001; T-test for dependent samples) was detected between the perceived quality of sleep of the three diurnal sleep categories compared to the three nocturnal sleep categories. Even thought the nurses slept (napped) during the night shift, their self-perceived alertness systematically decreased during it. Statistically significant differences were documented by one-way ANOVA (F=40.534 p<.0001) among the alertness measurements done during the night shift. In particular, there was significant difference in the level of perceived alertness (p<.0001) between the 7^th and 10^thh of the 12h night shift. These findings of decreased alertness during the terminal hours of the night shift are of concern, since they suggest risk of comprised patient care.     

Twelve-hour night shifts of healthcare workers: a risk to the patients?

We assessed the impact of 12h fixed night shift (19:00-07:00h) work, followed by 36h of off-time, on the sleep-wake cycle, sleep duration, self-perceived sleep quality, and work-time alertness on a group composed of 5 registered and 15 practical nurses. Wrist actigraphy (Ambulatory Monitoring, Inc.), with data analysis by the Cole-Kripke algorithm, was applied to determine sleep/wake episodes and their duration. The sleep episodes were divided into six categories: sleep during the night shift (x = 208.6; SD +/- 90.6 mins), sleep after the night shift (x = 138.7; SD +/- 79.6 min), sleep during the first night after the night work (x = 318.5; SD +/- 134.6 min), sleep before the night work (x = 104.3; SD +/- 44.1 min), diurnal sleep during the rest day (x = 70.5; SD +/- 43.0 min), and nocturnal sleep during the rest day (x = 310.4; SD +/- 188.9mins). A significant difference (p < .0001; T-test for dependent samples) was detected between the perceived quality of sleep of the three diurnal sleep categories compared to the three nocturnal sleep categories. Even thought the nurses slept (napped) during the night shift, their self-perceived alertness systematically decreased during it. Statistically significant differences were documented by one-way ANOVA (F = 40.534 p < .0001) among the alertness measurements done during the night shift. In particular, there was significant difference in the level of perceived alertness (p < .0001) between the 7th and 10th of the 12h night shift. These findings of decreased alertness during the terminal hours of the night shift are of concern, since they suggest risk of comprised patient care.     

Sleep/wake patterns and circadian typology in preschool children based on standardized parental self-reports

We studied the sleep/wake patterns and circadian typology of Japanese preschool children living in the Tokyo metropolitan area (193 boys and 190 girls, 4–6 years of age) from June to July 2012 based on a standardized parental self-reporting questionnaire. Our major findings are as follows: (1) sleep/wake timing was delayed, and the duration of nocturnal sleep (sleep period as well as time in bed) increased from that on scheduled days (weekdays) to that on free days (weekends) for all ages. (2) The duration of daily sleep (24?h), including daytime nap, was longer for 4-year-old children compared with that in 5- to 6-year-old children, but not significantly different between scheduled and free days within each age group. (3) The distribution of chronotypes was 36.3% for morning (M)-type, 48.8% for neither (N)-type and 11.2% for evening (E)-type, and this distribution was independent of sex or age. (4) Sleep/wake timing delays were observed from M-type and N-type to E-type during scheduled and free days. (5) The duration of nocturnal sleep decreased but increased for 24-h sleep time from M-type and N-type to E-type on scheduled days. (6) Sleep durations did not differ among chronotypes on free days. (7) Chronotypes were associated with parents’ diurnal preferences, mealtimes and attendance at kindergartens or childcare centers but not with sex, age, season of birth, exposure to multimedia or exposure to morning sunlight in their bedrooms. When these results were compared with those for older children and adolescents, similar sleep/wake patterns and circadian typology were observed, although to a lesser degree, in children as young as 4–6 years of age. Napping may compensate, in part, for an accumulated weekday sleep deficit. The distribution of chronotypes was associated with differences in sleep/wake timing and duration and was influenced by the parents’ diurnal preferences and lifestyles. Further research on preschool children is required to investigate whether circadian typology affects their behavioral, emotional and cognitive development.     

Alterations of locomotor activity rhythm and sleep parameters in patients with advanced glaucoma

The aim of this study was to evaluate the effect of advanced glaucoma on locomotor activity rhythms and related sleep parameters. Nine normal subjects and nine age-matched patients with bilateral advanced primary open-angle glaucoma, >10 yrs since diagnosis, were included in this observational, prospective, case-control study. Patients were required to record the timing and duration of their sleep and daily activities, and wore an actigraph on the wrist of the nondominant arm for 20 d. Activity rhythm period, MESOR (24-h time-series mean), amplitude (one-half peak-to-trough variation), and acrophase (peak time), plus long sleep episodes during the wake state, sleep duration, efficiency, and latency, as well as mean activity score, wake minutes, and mean wake episodes during the sleep interval were assessed in controls and glaucomatous patients. Glaucomatous patients exhibited significant decrease in nighttime sleep efficiency, and significant increase in the mean activity score, wake minutes, and mean wake episode during the night. These results suggest that alterations of circadian physiology could be a risk to the quality of life of patients with glaucoma.     

The internal circadian clock increases hunger and appetite in the evening independent of food intake and other behaviors

Objective:

Despite the extended overnight fast, paradoxically, people are typically not ravenous in the morning and breakfast is typically the smallest meal of the day. We assessed whether this paradox could be explained by an endogenous circadian influence on appetite with a morning trough, while controlling for sleep/wake and fasting/feeding effects.

Design and Methods:

Twelve healthy non‐obese adults (six males; age, 20‐42 years) were studied throughout a 13‐day laboratory protocol that balanced all behaviors, including eucaloric meals and sleep periods, evenly across the endogenous circadian cycle. Participants rated their appetite and food preferences by visual analog scales.

Results:

There was a large endogenous circadian rhythm in hunger, with the trough in the biological morning (8 AM) and peak in the biological evening (8 PM; peak‐to‐trough amplitude = 17%; P = 0.004). Similarly‐phased significant endogenous circadian rhythms were present in appetites for sweet, salty and starchy foods, fruits, meats/poultry, food overall, and for estimates of how much food participants could eat (amplitudes 14‐25%; all P < 0.05).

Conclusions:

In people who sleep at night, the intrinsic circadian evening peak in appetite may promote larger meals before the fasting period necessitated by sleep, whereas the circadian morning trough would theoretically facilitate the extended overnight fast. Furthermore, the circadian decline in hunger across the night would theoretically counteract the fasting‐induced hunger increase that could otherwise disrupt sleep.     

Alterations of Locomotor Activity Rhythm and Sleep Parameters in Patients With Advanced Glaucoma

The aim of this study was to evaluate the effect of advanced glaucoma on locomotor activity rhythms and related sleep parameters. Nine normal subjects and nine age-matched patients with bilateral advanced primary open-angle glaucoma, >10 yrs since diagnosis, were included in this observational, prospective, case-control study. Patients were required to record the timing and duration of their sleep and daily activities, and wore an actigraph on the wrist of the nondominant arm for 20 d. Activity rhythm period, MESOR (24-h time-series mean), amplitude (one-half peak-to-trough variation), and acrophase (peak time), plus long sleep episodes during the wake state, sleep duration, efficiency, and latency, as well as mean activity score, wake minutes, and mean wake episodes during the sleep interval were assessed in controls and glaucomatous patients. Glaucomatous patients exhibited significant decrease in nighttime sleep efficiency, and significant increase in the mean activity score, wake minutes, and mean wake episode during the night. These results suggest that alterations of circadian physiology could be a risk to the quality of life of patients with glaucoma. (Author correspondence: ruthr@fmed.uba.ar)     

The human endogenous circadian system causes greatest platelet activation during the biological morning independent of behaviors

Background

Platelets are involved in the thromboses that are central to myocardial infarctions and ischemic strokes. Such adverse cardiovascular events have day/night patterns with peaks in the morning (∼9AM), potentially related to endogenous circadian clock control of platelet activation. The objective was to test if the human endogenous circadian system influences (1) platelet function and (2) platelet response to standardized behavioral stressors. We also aimed to compare the magnitude of any effects on platelet function caused by the circadian system with that caused by varied standardized behavioral stressors, including mental arithmetic, passive postural tilt and mild cycling exercise.

Methodology/Principal Findings

We studied 12 healthy adults (6 female) who lived in individual laboratory suites in dim light for 240 h, with all behaviors scheduled on a 20-h recurring cycle to permit assessment of endogenous circadian function independent from environmental and behavioral effects including the sleep/wake cycle. Circadian phase was assessed from core body temperature. There were highly significant endogenous circadian rhythms in platelet surface activated glycoprotein (GP) IIb-IIIa, GPIb and P-selectin (6–17% peak-trough amplitudes; p≤0.01). These circadian peaks occurred at a circadian phase corresponding to 8–9AM. Platelet count, ATP release, aggregability, and plasma epinephrine also had significant circadian rhythms but with later peaks (corresponding to 3–8PM). The circadian effects on the platelet activation markers were always larger than that of any of the three behavioral stressors.

Conclusions/Significance

These data demonstrate robust effects of the endogenous circadian system on platelet activation in humans—independent of the sleep/wake cycle, other behavioral influences and the environment. The ∼9AM timing of the circadian peaks of the three platelet surface markers, including platelet surface activated GPIIb-IIIa, the final common pathway of platelet aggregation, suggests that endogenous circadian influences on platelet function could contribute to the morning peak in adverse cardiovascular events as seen in many epidemiological studies.     

The difference between in bed and out of bed activity as a behavioral marker of cancer patients: A comparative actigraphic study

The current study was conducted to provide normative data on actigraphic dichotomy index (I?<?O) (the percentage of in bed activity counts that are less than the median of out of bed counts) in healthy population and to assess whether the I?<?O could be an effective index in discriminating the circadian motor activity of cancer patients from healthy controls. In this retrospective study, we recovered 408 actigraphic records from two databases: healthy controls (n?=?182; 79 males; mean age 38.7?±?12.6) and patients with metastatic colorectal cancer (n?=?226; 149 males; mean age 58.4?±?11.4). Beside the usual actigraphic sleep parameters (time in bed, sleep onset latency, total sleep time, wake after sleep onset, sleep efficiency, number of awakenings, and mean motor activity), we also computed the dichotomy index and number of actigraphic wake parameters, namely, diurnal motor activity, diurnal total sleep time, number of sleep episodes, and the mean duration of the longest diurnal sleep episode. Using the Youden index, we calculated the cut off value that performed the best for I?<?O and actigraphic wake parameters. Finally, we created Receiver Operator Characteristic curves to test the efficacy of each actigraphic parameter to discriminate cancer patient from healthy controls. Mean I?<?O was 99.5% (SD, 0.48%) in the healthy group, as compared to 96.6% (SD, 3.6%) in the cancer group (p?<?0.0001). Important age-related effects appeared unlikely after performing both the main analysis with age as a covariate, and a subset analysis in 104 subjects matched for age and sex. In the main analysis, all actigraphic parameters, except total sleep time, significantly differentiated the two groups of participants. However, the I?<?O was the one that clearly performed best. Here, we provide the first large dataset on I?<?O in healthy subjects, we confirm the relevance of this circadian index for discriminating advanced stage colorectal cancer patients from healthy subjects, and we lay the grounds for further investigations of this circadian index in patients with other chronic diseases.     

Alertness and psychomotor performance levels of marine pilots on an irregular work roster

ABSTRACT

Fatigue is recognized as an important safety concern in the transportation industry. In this study, our goal was to investigate how circadian and sleep–wake dependent factors influence St-Lawrence River pilots’ sleep–wake cycle, alertness and psychomotor performance levels at work. A total of 18 male St-Lawrence River ship pilots were recruited to a 16–21-day field study. Pilots’ chronotype, sleepiness and insomnia levels were documented using standardized questionnaires. Their sleep–wake cycle was documented by a sleep–wake log and wrist-worn activity monitoring. Subjective alertness and objective psychomotor performances were assessed ~5×/day for each work and rest day. Ship transits were distributed throughout the 24-h day and lasted on average (± SEM) 5.93 ± 0.67 h. Main sleep periods occurred mainly at night, and objectively lasted 6.04 ± 1.02 h before work days. When going to bed at the end of work days, pilots subjectively reported sleeping 7.64 ± 1.64 h in the prior 24 h. Significant diurnal and wake-dependent effects were observed for subjective alertness and objective psychomotor performance, with minimum levels occurring between 09:00 and 10:00. Thus, despite their irregular work schedule, ship pilots presented, as a group, a diurnal variation of alertness and psychomotor performance indicative of a day-oriented circadian system. Important inter-individual differences were observed on psychomotor performance mesor and phase. In individuals, earlier phases in psychomotor performance were correlated with earlier chronotype. This study indicates that both circadian and homeostatic processes modulate alertness and psychomotor performance levels with worst levels reached when long shifts ended in the morning. This work has potential applications as it indicates fatigue countermeasures considering both processes are scientifically based.     

Dim Light at Night Does Not Disrupt Timing or Quality of Sleep in Mice

Artificial nighttime illumination has recently become commonplace throughout the world; however, in common with other animals, humans have not evolved in the ecological context of chronic light at night. With prevailing evidence linking the circadian, endocrine, immune, and metabolic systems, understanding these relationships is important to understanding the etiology and progression of several diseases. To eliminate the covariate of sleep disruption in light at night studies, researchers often use nocturnal animals. However, the assumption that light at night does not affect sleep in nocturnal animals remains unspecified. To test the effects of light at night on sleep, we maintained Swiss-Webster mice in standard light/dark (LD) or dim light at night (DLAN) conditions for 8–10 wks and then measured electroencephalogram (EEG) and electromyogram (EMG) biopotentials via wireless telemetry over the course of two consecutive days to determine differences in sleep timing and homeostasis. Results show no statistical differences in total percent time, number of episodes, maximum or average episode durations in wake, slow-wave sleep (SWS), or rapid eye movement (REM) sleep. No differences were evident in SWS delta power, an index of sleep drive, between groups. Mice kept in DLAN conditions showed a relative increase in REM sleep during the first few hours after the dark/light transition. Both groups displayed normal 24-h circadian rhythms as measured by voluntary running wheel activity. Groups did not differ in body mass, but a marked negative correlation of body mass with percent time spent awake and a positive correlation of body mass with time spent in SWS was evident. Elevated body mass was also associated with shorter maximum wake episode durations, indicating heavier animals had more trouble remaining in the wake vigilance state for extended periods of time. Body mass did not correlate with activity levels, nor did activity levels correlate with time spent in different sleep states. These data indicate that heavier animals tend to sleep more, potentially contributing to further weight gain. We conclude that chronic DLAN exposure does not significantly affect sleep timing or homeostasis in mice, supporting the use of dim light with nocturnal rodents in chronobiology research to eliminate the possible covariate of sleep disruption.     

Sleep/Wake Cycle Parameters and Sleep/Fatigue Complaints in Female Night Workers

Adaptation to shift-work is influenced by the way workers schedule their lives, including allocation of sleep episodes. Female workers (n = 29) engaged at an assembly line were studied as to individual differences in sleep parameters in order to verify whether those differences could be related to the manifestation of sleep and fatigue complaints. The sample was composed of women (20–40 y) working at night from Monday to Friday. Sleep data were based on daily sleep logs which were filled out by the workers for 10 consecutive weeks. In the analyses of sleep data both diurnal episodes between consecutive night shifts and noctural sleep episodes preceding working nights were taken into account. Worker's complaints were analyzed through questions extracted from an interview form encompassing questions on fatigue associated with the work schedule and on dissatisfaction with sleep on weekdays and weekends. The analysis of diurnal episodes showed no significant correlation between the total amount of sleep per day and the total number of complaints. Nevertheless, the latter was correlated to the length of the first sleep episode on a day, which usually began in the morning. As to sleep onset times, significant correlations were not detected concerning the first diurnal episodes. The analysis of nocturnal episodes did not reveal any significant correlation between sleep parameters and complaints. Results indicate that workers whose sleep onsets were allocated to the morning and were able to sleep for many consecutive hours, tended to show less complaints, suggesting that the temporal allocation of diurnal sleep and its length are relevant in the determination of how these workers perceive fatigue and sleep quality.     

Circadian Eating and Sleeping Patterns in the Night Eating Syndrome

Objective: To compare the eating and sleep‐wake patterns of persons with the night eating syndrome (NES) with those of matched control subjects. Research Methods and Procedures: Forty‐six overweight/obese NES subjects (mean age 43.3 ± 9.8 years; 32 women) and 43 similar controls (mean age 39.0 ± 11.0 years; 28 women) wore wrist actigraphs for 7 days and completed sleep and food diaries at home. Results: There was no difference between the total energy intake of the NES and the control subjects, but the pattern of energy intake differed greatly. Relative to control subjects, the temporal pattern of food intake of night eaters was delayed. Food intake after the evening meal, as a proportion of the 24‐hour intake, was more than 3‐fold greater in NES subjects than in controls (34.6 ± 10.1% vs. 10.0 ± 6.9%, p = 0.001). NES subjects had sleep onset, offset, and total sleep duration times comparable with those of controls. NES subjects reported more nocturnal awakenings than did controls (1.5 ± 1.0 per night vs. 0.5 ± 0.5; p < 0.001), and their actigraphically monitored arousals occurred earlier during sleep (at 128 minutes after sleep onset vs. 193 minutes, p = 0.01). NES subjects consumed food on 74% of the awakenings vs. 0% for the controls. Discussion: The pattern of cumulative energy intake of the night eaters suggests a phase delay in energy consumption relative to sleep‐wake times. NES may involve a dissociation of the circadian control of eating relative to sleep.     

The self-morningness/eveningness (Self-ME): An extremely concise and totally subjective assessment of diurnal preference

The assessment of diurnal preference, or the preferred timing of sleep and activity, is generally based on comprehensive questionnaires such as the Horne–Östberg (HÖ). The aim of the present study was to assess the reliability of a subject’s self-classification as extremely morning (Self-MM), more morning than evening (Self-M), more evening than morning (Self-E) or extremely evening (Self-EE) type, based on the last question of the HÖ (Self-ME). A convenience sample of 461 subjects [23.8?±?4.7 years; 322 females] completed a full sleep–wake assessment, including diurnal preference (HÖ), night sleep quality (Pittsburgh Sleep Quality Index, PSQI), daytime sleepiness (Karolinska Sleepiness Scale, KSS), and habitual sleep–wake timing (12?d sleep diaries; n?=?296). Significant differences in HÖ total score were observed between Self-ME classes, with each class being significantly different from neighboring classes (p?<?0.0001). Significant differences in sleep–wake timing (bed time, try to sleep and sleep onset, wake up, and get up time) were observed between Self-ME classes. Such differences were maintained when sleep–wake habits were analysed separately on work and free days, and also in a smaller group of 67 subjects who completed the Self-ME as a stand-alone rather than as part of the original questionnaire. Significant differences were observed in the time-course of subjective sleepiness by Self-ME class in both the large and the small group, with Self-MM and Self-M subjects being significantly more alert in the morning and sleepier in the evening hours compared with their Self-E and Self-EE counterparts. Finally, significant differences were observed in night sleep quality between Self-ME classes, with Self-EE/Self-E subjects sleeping worse than their Self-MM/Self-M counterparts, and averaging just over the abnormality PSQI threshold of 5. In conclusion, young, healthy adults can define their diurnal preference based on a single question (Self-ME) in a way that reflects their sleep–wake timing, their sleepiness levels over the daytime hours, and their night sleep quality. Validation of the Self-ME across the decades and in diseased populations seems worthy.     

Sleep/Wake Cycle Parameters and Sleep/Fatigue Complaints in Female Night Workers

Adaptation to shift-work is influenced by the way workers schedule their lives, including allocation of sleep episodes. Female workers ( n = 29) engaged at an assembly line were studied as to individual differences in sleep parameters in order to verify whether those differences could be related to the manifestation of sleep and fatigue complaints. The sample was composed of women (20-40 y) working at night from Monday to Friday. Sleep data were based on daily sleep logs which were filled out by the workers for 10 consecutive weeks. In the analyses of sleep data both diurnal episodes between consecutive night shifts and noctural sleep episodes preceding working nights were taken into account. Worker's complaints were analyzed through questions extracted from an interview form encompassing questions on fatigue associated with the work schedule and on dissatisfaction with sleep on weekdays and weekends. The analysis of diurnal episodes showed no significant correlation between the total amount of sleep per day and the total number of complaints. Nevertheless, the latter was correlated to the length of the first sleep episode on a day, which usually began in the morning. As to sleep onset times, significant correlations were not detected concerning the first diurnal episodes. The analysis of nocturnal episodes did not reveal any significant correlation between sleep parameters and complaints. Results indicate that workers whose sleep onsets were allocated to the morning and were able to sleep for many consecutive hours, tended to show less complaints, suggesting that the temporal allocation of diurnal sleep and its length are relevant in the determination of how these workers perceive fatigue and sleep quality.     

Daily distribution of sleep states in the rookCorvus frugilegus

Summary Sleep and wake states were monitored polygraphically in the rookCorvus frugilegus, under the natural photoperiod and temperature. The indices of sleep and wake states in the rook were similar to those described previously for birds in general. The appearance of sleep episodes was confined to the dark part of the photoperiod. Slow wave sleep (SWS) showed a tendency to increase during the course of the night, while paradoxical sleep (PS) showed the opposite trend. The distribution of short SWS episodes were clustered into two groups, one group occurred in the period following the onset of sleep and the other, less prominent group occurred towards the end of sleep. The longest episodes of SWS appeared in the second half of the night, whereas those of PS appeared after onset of sleep.Abbreviations EMG electromyogram - EOG electrooculogram - PS paradoxical sleep - SWS slow wave sleep - W wake state     

Contribution of circadian physiology and sleep homeostasis to age-related changes in human sleep

The circadian pacemaker and sleep homeostasis play pivotal roles in vigilance state control. It has been hypothesized that age-related changes in the human circadian pacemaker, as well as sleep homeostatic mechanisms, contribute to the hallmarks of age-related changes in sleep, that is, earlier wake time and reduced sleep consolidation. Assessments of circadian parameters in healthy young (∼20-30 years old) and older people (∼65-75 years old)—in the absence of the confounding effects of sleep, changes in posture, and light exposure—have demonstrated that an earlier wake time in older people is accompanied by about a 1h advance of the rhythms of core body temperature and melatonin. In addition, older people wake up at an earlier circadian phase of the body temperature and plasma melatonin rhythm. The amplitude of the endogenous circadian component of the core body temperature rhythm assessed during constant routine and forced desynchrony protocols is reduced by 20-30% in older people. Recent assessments of the intrinsic period of the human circadian pacemaker in the absence of the confounding effects of light revealed no age-related reduction of this parameter in both sighted and blind individuals. Wake maintenance and sleep initiation are not markedly affected by age except that sleep latencies are longer in older people when sleep initiation is attempted in the early morning. In contrast, major age-related reductions in the consolidation and duration of sleep occur at all circadian phases. Sleep of older people is particularly disrupted when scheduled on the rising limb of the temperature rhythm, indicating that the sleep of older people is more susceptible to arousal signals genernpated by the circadian pacemaker. Sleep-homeostatic mechanisms, as assayed by the sleep-deprivation-induced increase of EEG slow-wave activity (SWA), are operative in older people, although during both baseline sleep and recovery sleep SWA in older people remains at lower levels. The internal circadian phase advance of awakening, as well as the age-related reduction in sleep consolidation, appears related to an age-related reduction in the promotion of sleep by the circadian pacemaker during the biological night in combination with a reduced homeostatic pressure for sleep. Early morning light exposure associated with this advance of awakening in older people could reinforce the advanced circadian phase. Quantification of the interaction between sleep homeostasis and circadian rhythmicity contributes to understanding age-related changes in sleep timing and quality. (Chronobiology International, 17(3), 285-311, 2000)     

Working Under Daylight Intensity Lamp: An Occupational Risk for Developing Circadian Rhythm Sleep Disorder?

A 47‐yr‐old male was admitted to the Institute for Fatigue and Sleep Medicine complaining of severe fatigue and daytime sleepiness. His medical history included diagnosis of depression and chronic fatigue syndrome. Antidepressant drugs failed to improve his condition. He described a gradual evolvement of an irregular sleep‐wake pattern within the past 20 yrs, causing marked distress and severe impairment of daily functioning. He had to change to a part‐time position 7 yrs ago, because he was unable to maintain a regular full‐time job schedule. A 10‐day actigraphic record revealed an irregular sleep-wake pattern with extensive day‐to‐day variability in sleep onset time and sleep duration, and a 36 h sampling of both melatonin level and oral temperature (12 samples, once every 3 h) showed abnormal patterns, with the melatonin peak around noon and oral temperature peak around dawn. Thus, the patient was diagnosed as suffering from irregular sleep‐wake pattern. Treatment with melatonin (5 mg, 2 h before bedtime) did not improve his condition. A further investigation of the patient's daily habits and environmental conditions revealed two important facts. First, his occupation required work under a daylight intensity lamp (professional diamond‐grading equipment of more than 8000 lux), and second, since the patient tended to work late, the exposure to bright light occurred mostly at night. To recover his circadian rhythmicity and stabilize his sleep‐wake pattern, we recommended combined treatment consisting of evening melatonin ingestion combined with morning (09:00 h) bright light therapy (0800 lux for 1 h) plus the avoidance of bright light in the evening. Another 10‐day actigraphic study done only 1 wk after initiating the combined treatment protocol revealed stabilization of the sleep‐wake pattern with advancement of sleep phase. In addition, the patient reported profound improvement in maintaining wakefulness during the day. This case study shows that chronic exposure to bright light at the wrong biological time, during the nighttime, may have serious effects on the circadian sleep‐wake patterns and circadian time structure. Therefore, night bright light exposure must be considered to be a risk factor of previously unrecognized occupational diseases of altered circadian time structure manifested as irregularity of the 24 h sleep‐wake cycle and melancholy.     

THE HAMSTER CLOCK PHASE-RESPONSE CURVE FROM SUMMERLIKE LIGHT:DARK CYCLES AND ITS ROLE IN DAILY AND SEASONAL TIMEKEEPING

We address the subject of entrainment of the hamster clock by the day:night cycle in summer when the sun sets after 6 PM and rises before 6 AM (nights<12 h). Summer day:night cycles were simulated by 6 light:dark (LD) cycles with D<12 h (summerlike, SLD) ranging from SLD 12.5h:11.5h (D, 6:15 PM–5:45 AM) to 18h:6h (D, 9 PM–3 AM). These are the near limiting SLDs for constant PM timing (entrainment) of behavioral estrus and wheel running in hamsters. The onset of estrus was observed every 4 d in the same hamsters as a phase marker of their 24h clock. On the day before an experimental estrus, preceded and followed by control onsets, a dark period was imposed to cover a putative 6 PM–6 AM light-sensitive period (LSP). This was scanned with a light pulse (and periodic 5sec bell alarms) lasting 5–240 min. Shifts in onset of estrus on the next day were plotted vs. the end of the light pulse for PM times (“dusk”) and its onset for AM times (“dawn”). The resulting phase shifts from the six SLDs were similar, permitting their combination into a single phase-response curve (PRC) of 1605 shifts. This SLD composite PRC rose at 10:15 PM, peaked at 2 AM (81min advanced shift), fell linearly to 5:55 AM, and then abruptly to normal at 6 AM (no shift). Peak shift was unaffected by light pulse duration or intensity, or hamster age. The SLD composite PRC lacked the 6 PM–9 PM curve of delayed shifts present in reported PRCs from LD 12h:12h and DD. However, a two-pulse experiment showed that all light from 6 PM to L-off was needed to block (balance) the advancing action of a 5min morning light pulse, thereby maintaining entrainment. A working hypothesis to explain daily entrainment and seasonal fertility in the golden hamster is illustrated. A nomenclature for labeling the phases of the hamster clock (circadian time) is proposed.     

Aging in Mice Reduces the Ability to Sustain Sleep/Wake States

One of the most significant problems facing older individuals is difficulty staying asleep at night and awake during the day. Understanding the mechanisms by which the regulation of sleep/wake goes awry with age is a critical step in identifying novel therapeutic strategies to improve quality of life for the elderly. We measured wake, non-rapid eye movement (NREM) and rapid-eye movement (REM) sleep in young (2–4 months-old) and aged (22–24 months-old) C57BL6/NIA mice. We used both conventional measures (i.e., bout number and bout duration) and an innovative spike-and-slab statistical approach to characterize age-related fragmentation of sleep/wake. The short (spike) and long (slab) components of the spike-and-slab mixture model capture the distribution of bouts for each behavioral state in mice. Using this novel analytical approach, we found that aged animals are less able to sustain long episodes of wakefulness or NREM sleep. Additionally, spectral analysis of EEG recordings revealed that aging slows theta peak frequency, a correlate of arousal. These combined analyses provide a window into the mechanisms underlying the destabilization of long periods of sleep and wake and reduced vigilance that develop with aging.     

CONTRIBUTION OF CIRCADIAN PHYSIOLOGY AND SLEEP HOMEOSTASIS TO AGE-RELATED CHANGES IN HUMAN SLEEP

The circadian pacemaker and sleep homeostasis play pivotal roles in vigilance state control. It has been hypothesized that age-related changes in the human circadian pacemaker, as well as sleep homeostatic mechanisms, contribute to the hallmarks of age-related changes in sleep, that is, earlier wake time and reduced sleep consolidation. Assessments of circadian parameters in healthy young (～20–30 years old) and older people (～65–75 years old)—in the absence of the confounding effects of sleep, changes in posture, and light exposure—have demonstrated that an earlier wake time in older people is accompanied by about a 1h advance of the rhythms of core body temperature and melatonin. In addition, older people wake up at an earlier circadian phase of the body temperature and plasma melatonin rhythm. The amplitude of the endogenous circadian component of the core body temperature rhythm assessed during constant routine and forced desynchrony protocols is reduced by 20–30% in older people. Recent assessments of the intrinsic period of the human circadian pacemaker in the absence of the confounding effects of light revealed no age-related reduction of this parameter in both sighted and blind individuals. Wake maintenance and sleep initiation are not markedly affected by age except that sleep latencies are longer in older people when sleep initiation is attempted in the early morning. In contrast, major age-related reductions in the consolidation and duration of sleep occur at all circadian phases. Sleep of older people is particularly disrupted when scheduled on the rising limb of the temperature rhythm, indicating that the sleep of older people is more susceptible to arousal signals genernpated by the circadian pacemaker. Sleep-homeostatic mechanisms, as assayed by the sleep-deprivation–induced increase of EEG slow-wave activity (SWA), are operative in older people, although during both baseline sleep and recovery sleep SWA in older people remains at lower levels. The internal circadian phase advance of awakening, as well as the age-related reduction in sleep consolidation, appears related to an age-related reduction in the promotion of sleep by the circadian pacemaker during the biological night in combination with a reduced homeostatic pressure for sleep. Early morning light exposure associated with this advance of awakening in older people could reinforce the advanced circadian phase. Quantification of the interaction between sleep homeostasis and circadian rhythmicity contributes to understanding age-related changes in sleep timing and quality. (Chronobiology International, 17(3), 285–311, 2000)