Benita Middleton

The light levels required to maintain human circadian phase in the absence of other strong time cues are not defined. We investigated circadian phase in two groups of men, living in partial temporal isolation, exposed to 12 h:12 h light:dark cycles of: (A) 200: <8 lux, broad spectrum white light for 14 days; and (B) 1000: <8lux for 14 days. The rhythm variables measured were urinary 6-sulphatoxymelatonin, rectal temperature, activity and rest (actigraphy and sleep logs). In 200: <8 lux four/six individuals showed phase delays. Exposure to 1000: <8 lux appeared to maintain synchronisation of rest-activity to 24 h, but with a significant overall phase advance of 0.81 h in temperature. These observations suggest that domestic intensity light does not maintain phase without scheduled sleep/activity, possibly due to indirect effects on behaviour influencing light exposure.

In humans, the pineal hormone melatonin can phase shift a number of circadian rhythms (e.g., "fatigue", endogenous melatonin, core body temperature) together with the timing of prolactin secretion. It is uncertain, however, whether melatonin can fully entrain all human circadian rhythms. In this study, the authors investigated the effects of daily melatonin administration on sighted individuals kept in continuous very dim light. A total of 10 normal, healthy males were maintained in two separate groups in partial temporal isolation under constant dim light (< 8 lux) with attenuated sound and ambient temperature variations but with knowledge of clock time for two periods of 30 days. In these circumstances, the majority of individuals free run with a mean period of 24.3 h. In a double-blind, randomized crossover design, subjects received 5 mg melatonin at 20:00 h on Days 1 to 15 (Melatonin 1st) followed by placebo on Days 16 to 30 (Placebo 2nd) or vice versa (Placebo 1st,...

It has been suggested that circadian rhythm disturbances are present after major surgery and that this may play a role in the development of postoperative sleep disturbances, fatigue, cognitive dysfunction and cardiovascular morbidity. The objective of this study was to examine the profile of melatonin, cortisol and core body temperature rhythms before and after major surgery. Blood samples (melatonin and cortisol) and core body temperature readings were collected every hour in the 24-h period prior to surgery and the 48 h after surgery from 11 patients undergoing major abdominal surgery. All patients had private rooms. Light exposure was controlled and monitored. Phase markers [50% dim light melatonin onset (DLMO 50%) and offset (DLMOff 50%), cortisol and core body temperature acrophase] for the three circadian rhythm profiles were calculated before and after surgery. The correlation between the melatonin rhythm and time of surgery, duration of surgery and opioid use was examined. A median delay in the onset of melatonin was seen on the first postoperative day [median DLMO 50% 22:46 hours (range: 21:15-01:08 hours) on the preoperative day compared with 23:54 hours (range: 19:09-02:46 hours) on the first postoperative day; P </= 0.05] . A significant positive correlation existed between the duration of surgery and the time of melatonin onset (r = 0.67, P </= 0.05) . There was a significantly reduced basal secretion of melatonin immediately after surgery, with a subsequent significant increase in maximum melatonin values on the second postoperative night. A median delay of up to 4 h was seen in the timing of the peak of the temperature rhythm on the second postoperative day. Both cortisol secretion and core body temperature were increased after surgery and did not return to preoperative values in the 48 h of the postoperative study period. No significant correlation between opioid dose and the basal or maximum melatonin levels or the time of melatonin onset was found. We found disturbances in three circadian markers after major surgery. The clinical consequences of postoperative circadian disturbances should be investigated further in the future.

The pineal hormone melatonin is a popular treatment for sleep and circadian rhythm disruption. Melatonin administered at optimal times of the day for treatment often results in a prolonged melatonin profile. In photoperiodic (day length-dependent) species, changes in melatonin profile duration influence the timing of seasonal rhythms. We investigated the effects of an artificially prolonged melatonin profile on endogenous melatonin and cortisol rhythms, wrist actigraphy, and reproductive hormones in humans. Eight healthy men took part in this double-blind, crossover study. Surge/sustained release melatonin (1.5 mg) or placebo was administered for 8 d at the beginning of a 16-h sleep opportunity (1600 h to 0800 h) in dim light. Compared with placebo, melatonin administration advanced the timing of endogenous melatonin and cortisol rhythms. Activity was reduced in the first half and increased in the second half of the sleep opportunity with melatonin; however, total activity during the sleep opportunities and wake episodes was not affected. Melatonin treatment did not affect the endogenous melatonin profile duration, pituitary/gonadal hormone levels (24-h), or sleepiness and mood levels on the subsequent day. In the short term, suitably timed sustained-release melatonin phase-shifts circadian rhythms and redistributes activity during a 16-h sleep opportunity, with no evidence of changes in the duration of endogenous melatonin secretion or pituitary/gonadal hormones.

Numerous factors influence the increased health risks of seamen. This study investigated sleep (by actigraphy) and the adaptation of the internal clock in watch-keeping crew compared to day workers, as possible contributory factors. Fourteen watch keepers, 4 h on, 8 h off (0800-1200/2000-2400 h, 1200-1600/2400-0400 h, 1600-2000/0400-0800 h) (fixed schedule, n = 6; rotating by delay weekly, n = 8), and 12 day workers participated during a voyage from the United Kingdom to Antarctica. They kept daily sleep diaries and wore wrist monitors for continuous recording of activity. Sleep parameters were derived from activity using the manufacturer's software and analyzed by repeated-measures ANOVA using SAS 8.2. Sequential urine samples were collected for 48 h weekly for 6-sulphatoxymelatonin measurement as an index of circadian rhythm timing. Individuals working watches of 1200-1600/2400-0400 h and 1600-2000/0400-0800 h had 2 sleeps daily, analyzed separately as main sleep (longest) and 2nd sleep. Main sleep duration was shorter in watch keepers than in day workers (p < 0.0001). Objective sleep quality was significantly compromised in rotaters compared to both day workers and fixed watch keepers, the most striking comparisons being sleep efficiency (percentage desired sleep time spent sleeping) main sleep (p < 0.0001) and sleep fragmentation (an index of restlessness) main sleep (p < 0.0001). The 2nd sleep was substantially less efficient than was the main sleep (p < 0.0001) for all watch keepers. There were few significant differences in sleep between the different watches in rotating watch keepers. Circadian timing remained constant in day workers. Timing of the 6-sulphatoxymelatonin rhythm was later for the watch of 1200-1600/2400-0400 h than for all others (1200-1600/2400-0400 h, 5.90 +/- 0.85 h; 1600-2000/0400-0800 h, 1.5 +/- 0.64 h; 0800-1200/ 2000-2400 h, 2.72 +/- 0.76 h; days, 2.09 +/- 0.68 h [decimal hours, mean +/- SEM]: ANOVA, p < 0.01). This study identifies weekly changes in watch time as a cause of poor sleep in watch keepers. The most likely mechanism is the inability of the internal clock to adapt rapidly to abrupt changes in schedule.

Melatonin has chronobiotic properties in humans. It is able to phase shift strongly endogenous rhythms, such as core temperature and its own endogenous rhythm, together with the sleep-wake cycle. Its ability to synchronize free-running rhythms has not been fully investigated in humans. There is evidence for synchronization of the sleep-wake cycle, but the available data suggest that it is less effective with regard to endogenous melatonin and core temperature rhythms. When suitably timed, most studies indicate that fast release preparations are able to hasten adaptation to phase shift in both field and simulation studies of jet lag and shift work. Both subjective and objective measures support this statement. However, not all studies have been successful. Careful evaluation of the effects on work-related performance is required. When used to alleviate the non-24-h sleep-wake disorder in blind subjects, again most studies report a successful outcome using behavioral measures, albeit in a small number of individuals. The present data suggest, however, that although sleep-wake can be stabilized to 24 h, entrainment of other rhythms is exceptionally rare.

Antarctic Base personnel live for 3 months in winter with no natural sunlight. This project compared sleep, by actigraphy, during periods of increased exposure to white light or blue enriched light in 2003. The primary aim was to help define the optimum spectral composition and intensity of artificial environmental light. Nine men and one woman (33 +/- 7 years, mean +/- SD), wore activity and light monitors continuously from 28.2 to 9.10, and kept sleep diaries. Extra light was provided by light boxes (standard white, 5300 K, or prototype blue enriched, 10,000 K, Philips Lighting), which were turned on in bedrooms and in communal/work areas approximately 08.00-18.00 hours. After a no-treatment control period, 28.2-20.3, sequential 4-5 week periods of first white, then blue light, were imposed with a further control period 19.9-9.10. A limited baseline study in 2002 (no interventions) similarly measured light and activity in seven men and one woman (30 +/- 7 years). Daily light expos...

Sleep disturbances are common in patients with cirrhosis but their origins are unknown. The aim of this study was to investigate possible involvement of the circadian system. Sleep was monitored for two weeks, in the home environment, using sleep diaries and actigraphy, in 35 patients with cirrhosis (21 men; mean age [+/- 1SD] 58 +/- 10 yr) and 12 matched healthy controls (eight men; mean age 56 +/- 15 yr); urinary 6-sulphatoxymelatonin (aMT6s), the major metabolite of melatonin, was measured over 56 h, to assess circadian rhythmicity. The patients woke up and got up significantly later than the healthy volunteers and their sleep was significantly more fragmented. Mean 24-hour urinary aMT6s outputs were comparable in the patients and controls (15.5 +/- 13.1 vs. 20.3 +/- 13.8 microg/24 h) but were significantly lower in the decompensated patients (9.8 +/- 11.3 vs. 17.0 +/- 13.3 microg/24 h; p = 0.03). Significant 24-hour urinary aMT6s rhythms were observed in 26 (79%) of the 33 patie...

Delayed sleep phase (and sometimes free-run) is common in the Antarctic winter (no natural sunlight) and optimizing the artificial light conditions is desirable. This project evaluated sleep when using 17,000 K blue-enriched lamps compared with standard white lamps (5000 K) for personal and communal illumination. Base personnel, 10 males, five females, 32.5±8 years took part in the study. From 24 March to 21 September 2006 light exposure alternated between 4-5-week periods of standard white (5000 K) and blue-enriched lamps (17,000 K), with a 3-week control before and after extra light. Sleep and light exposure were assessed by actigraphy and sleep diaries. General health (RAND 36-item questionnaire) and circadian phase (urinary 6-sulphatoxymelatonin rhythm) were evaluated at the end of each light condition. Direct comparison (rmanova) of blue-enriched light with white light showed that sleep onset was earlier by 19 min (P=0.022), and sleep latency tended to be shorter by 4 min (P=0....

Sleep disruption is a commonly encountered clinical feature in schizophrenic patients, and one important concern is to determine the extent of this disruption under "real" life situations. Simultaneous wrist actigraphy, diary records, and repeated urine collection for urinary 6-sulphatoxymelatonin (aMT6s) profiles are appropriate tools to assess circadian rhythms and sleep patterns in field studies. Their suitability for long-term recordings of schizophrenic patients living in the community has not been evaluated. In this case report, we document long-term simultaneous wrist actigraphy, light detection, repeated urine collection, and diary records as a suitable combination of non-invasive techniques to quantify and assess changes in sleep-wake cycles, light exposure, and melatonin profiles in a schizophrenic patient. The actigraph was well-tolerated by the patient, and compliance to diary records and 48 h urine collection was particularly good with assistance from family members. The data obtained by these techniques are illustrated, and the results reveal remarkable abnormal patterns of rest-activity patterns, light exposure, and melatonin production. We observed various rest-activity patterns, including phase-shifts, highly delayed sleep on- and offsets, and irregular rest-activity phases. The period of the rest-activity rhythm, light-dark cycle, and melatonin rhythm was longer than 24 h. These circadian abnormalities may reinforce the altered sleep patterns and the problems of cognitive function and social engagement associated with schizophrenic.