Helen J. Burgess

Sleep and circadian influences on cardiac autonomic nervous system activity

To assess the separate contributions of the sleep and circadian systems to changes in cardiac autonomic nervous system (ANS) activity, 12 supine subjects participated in two 26-h constant routines, which were counterbalanced and separated by 1 wk. One routine did not permit sleep, whereas the second allowed the subjects to sleep during their normal sleep phase. Parasympathetic nervous system activity was assessed with respiratory sinus arrhythmia as measured from the spectral analysis of cardiac beat-to-beat intervals. Sympathetic nervous system activity was primarily assessed with the preejection period as estimated from impedance cardiography, although the 0.1-Hz peak from the spectral analysis of cardiac beat-to-beat intervals, the amplitude of the T wave in the electrocardiogram, and heart rate were also measured. Respiratory sinus arrhythymia showed a 24-h rhythm independent of sleep, whereas preejection period only showed a 24-h rhythm if sleep occurred. Thus the findings indicate that parasympathetic nervous system activity is mostly influenced by the circadian system, whereas sympathetic nervous system activity is mostly influenced by the sleep system.To assess the separate contributions of the sleep and circadian systems to changes in cardiac autonomic nervous system (ANS) activity, 12 supine subjects participated in two 26-h constant routines, which were counterbalanced and separated by 1 wk. One routine did not permit sleep, whereas the second allowed the subjects to sleep during their normal sleep phase. Parasympathetic nervous system activity was assessed with respiratory sinus arrhythmia as measured from the spectral analysis of cardiac beat-to-beat intervals. Sympathetic nervous system activity was primarily assessed with the preejection period as estimated from impedance cardiography, although the 0.1-Hz peak from the spectral analysis of cardiac beat-to-beat intervals, the amplitude of the T wave in the electrocardiogram, and heart rate were also measured. Respiratory sinus arrhythymia showed a 24-h rhythm independent of sleep, whereas preejection period only showed a 24-h rhythm if sleep occurred. Thus the findings indicate that parasympathetic nervous system activity is mostly influenced by the circadian system, whereas sympathetic nervous system activity is mostly influenced by the sleep system.

Individual Differences in the Amount and Timing of Salivary Melatonin Secretion

Background The aim of this study was to examine individual differences in a large sample of complete melatonin profiles not suppressed by light and search for possible associations between the amount and timing of melatonin secretion and a multitude of lifestyle variables. The melatonin profiles were derived from saliva samples collected every 30 minutes in dim light from 85 healthy women and 85 healthy men aged 18–45 years. There was a large individual variability in the amount of melatonin secreted with peak values ranging from 2 to 84 pg/ml. The onset of melatonin secretion ranged from 18:13 to 00:26 hours. The use of hormonal birth control, reduced levels of employment, a smaller number of days on a fixed sleep schedule, increased day length and lower weight were associated with an increased amplitude of melatonin secretion. The use of hormonal birth control, contact lenses, a younger age, and lower ratings of mania and paranoia were associated with a longer duration of melatonin secretion. An earlier occurrence of the onset of melatonin secretion was associated with an earlier wake time, more morningness and the absence of a bed partner. Lifestyle and behavioral variables were only able to explain about 15% of the individual variability in the amount of melatonin secretion, which is likely because of a substantial genetic influence on the levels of melatonin secretion.

Preflight Adjustment to Eastward Travel: 3 Days of Advancing Sleep with and without Morning Bright Light

Jet lag is caused by a misalignment between circadian rhythms and local destination time. As humans typically take longer to re-entrain after a phase advance than a phase delay, eastward travel is often more difficult than westward travel. Previous strategies to reduce jet lag have focused on shaping the perceived light-dark cycle after arrival, in order to facilitate a phase shift in the appropriate direction. Here we tested treatments that travelers could use to phase advance their circadian rhythms prior to eastward flight. Thus, travelers would arrive with their circadian rhythms already partially re-entrained to local time. We determined how far the circadian rhythms phase advanced, and the associated side effects related to sleep and mood. Twenty-eight healthy young subjects participated in 1 of 3 different treatments, which all phase advanced each subjects habitual sleep schedule by 1 h/day for 3 days. The 3 treatments differed in morning light exposure for the 1st 3.5 h after waking on each of the 3 days: continuous bright light (> 3000 lux), intermittent bright light (> 3000 lux, 0.5 h on, 0.5 off, etc.), or ordinary dim indoor light (< 60 lux). A phase assessment in dim light (< 10 lux) was conducted before and after the treatments to determine the endogenous salivary dim light melatonin onset (DLMO). The mean DLMO phase advances in the dim, intermittent, and continuous light groups were 0.6, 1.5, and 2.1 h, respectively. The intermittent and continuous light groups advanced significantly more than the dim light group (p < 0.01) but were not significantly different from each other. The side effects as assessed with actigraphy and logs were small. A 2-h phase advance may seem small compared to a 6- to 9-h time zone change, as occurs with eastward travel from the USA to Europe. However, a small phase advance will not only reduce the degree of re-entrainment required after arrival, but may also increase postflight exposure to phase-advancing light relative to phase-delaying light, thereby reducing the risk of antidromic re-entrainment. More days of preflight treatment could be used to produce even larger phase advances and potentially eliminate jet lag.

A three pulse phase response curve to three milligrams of melatonin in humans

Exogenous melatonin is increasingly used for its phase shifting and soporific effects. We generated a three pulse phase response curve (PRC) to exogenous melatonin (3 mg) by administering it to free‐running subjects. Young healthy subjects (n= 27) participated in two 5 day laboratory sessions, each preceded by at least a week of habitual, but fixed sleep. Each 5 day laboratory session started and ended with a phase assessment to measure the circadian rhythm of endogenous melatonin in dim light using 30 min saliva samples. In between were three days in an ultradian dim light (< 150 lux)–dark cycle (LD 2.5 : 1.5) during which each subject took one pill per day at the same clock time (3 mg melatonin or placebo, double blind, counterbalanced). Each individuals phase shift to exogenous melatonin was corrected by subtracting their phase shift to placebo (a free‐run). The resulting PRC has a phase advance portion peaking about 5 h before the dim light melatonin onset, in the afternoon. The phase delay portion peaks about 11 h after the dim light melatonin onset, shortly after the usual time of morning awakening. A dead zone of minimal phase shifts occurred around the first half of habitual sleep. The fitted maximum advance and delay shifts were 1.8 h and 1.3 h, respectively. This new PRC will aid in determining the optimal time to administer exogenous melatonin to achieve desired phase shifts and demonstrates that using exogenous melatonin as a sleep aid at night has minimal phase shifting effects.

Human Phase Response Curves to Three Days of Daily Melatonin: 0.5 mg Versus 3.0 mg

CONTEXT Phase response curves (PRCs) to melatonin exist, but none compare different doses of melatonin using the same protocol. OBJECTIVE The aim was to generate a PRC to 0.5 mg of oral melatonin and compare it to our previously published 3.0 mg PRC generated using the same protocol. DESIGN AND SETTING The study included two 5-d sessions in the laboratory, each preceded by 7-9 d of fixed sleep times. Each session started and ended with a phase assessment to measure the dim light melatonin onset (DLMO). In between were 3 d in an ultradian dim light (<150 lux)/dark cycle (light:dark, 2.5:1.5). PARTICIPANTS Healthy adults (16 men, 18 women) between the ages of 18 and 42 yr participated in the study. INTERVENTIONS During the ultradian days of the laboratory sessions, each participant took one pill per day at the same clock time (0.5 mg melatonin or placebo, double blind, counterbalanced). MAIN OUTCOME MEASURE Phase shifts to melatonin were derived by subtracting the phase shift to placebo. A PRC with time of pill administration relative to baseline DLMO and a PRC relative to midpoint of home sleep were generated. RESULTS Maximum advances occurred when 0.5 mg melatonin was taken in the afternoon, 2-4 h before the DLMO, or 9-11 h before sleep midpoint. The time for maximum phase delays was not as distinct, but a fitted curve peaked soon after wake time. CONCLUSIONS The optimal administration time for advances and delays is later for the lower dose of melatonin. When each dose of melatonin is given at its optimal time, both yield similarly sized advances and delays.

The dim light melatonin onset following fixed and free sleep schedules

The time at which the dim light melatonin onset (DLMO) occurs can be used to ensure the correct timing of light and/or melatonin administration in order to produce desired circadian phase shifts. Sometimes however, measuring the DLMO is not feasible. Here we determined if the DLMO was best estimated from fixed sleep times (based on habitual sleep times) or free (ad libitum) sleep times. Young healthy sleepers on fixed (n = 60) or free (n = 60) sleep schedules slept at home for 6 days. Sleep times were recorded with sleep logs verified with wrist actigraphy. Half‐hourly saliva samples were then collected during a dim light phase assessment and were later assayed to determine the DLMO. We found that the DLMO was more highly correlated with sleep times in the free sleepers than in the fixed sleepers (DLMO versus wake time, r = 0.70 and r = 0.44, both P < 0.05). The regression equation between wake time and the DLMO in the free sleepers predicted the DLMO in an independent sample of free sleepers (n = 23) to within 1.5 h of the actual DLMO in 96% of cases. These results indicate that the DLMO can be readily estimated in people whose sleep times are minimally affected by work, class and family commitments. Further work is necessary to determine if the DLMO can be accurately estimated in people with greater work and family responsibilities that affect their sleep times, perhaps by using weekend wake times, and if this method will apply to the elderly and patients with circadian rhythm disorders.

The impact of a week of simulated night work on sleep, circadian phase, and performance

Aims: To investigate factors that may contribute to performance adaptation during permanent night work. Methods: Fifteen healthy subjects participated in an adaptation and baseline night sleep, directly followed by seven simulated eight-hour night shifts (2300 to 0700 hours). At the end of each shift they were taken outside and exposed to natural light for 20 minutes. They then slept from approximately 0800 hours until they naturally awoke. Results: There was a significant increase in mean performance on a visual psychomotor vigilance task across the week. Daytime sleep quality and quantity were not negatively affected. Total sleep time (TST) for each of the daytime sleeps was reduced, resulting in an average cumulative sleep debt of 3.53 hours prior to the final night shift. TST for each of the daytime sleep periods did not significantly differ from the baseline night, nor did TST significantly vary across the week. There was a significant decrease in wake time after sleep onset and sleep onset latency across the week; sleep efficiency showed a trend towards greater efficiency across the consecutive daytime sleeps. Hours of wakefulness prior to each simulated night shift significantly varied across the week. The melatonin profile significantly shifted across the week. Conclusions: Results suggest that under optimal conditions, the sleep debt that accumulates during consecutive night shifts is relatively small and does not exacerbate decrements in night-time performance resulting from other factors. When sleep loss is minimised, adaptation of performance during consecutive night shifts can occur in conjunction with circadian adaptation.

The Relationship Between the Dim Light Melatonin Onset and Sleep on a Regular Schedule in Young Healthy Adults

The endogenous melatonin onset in dim light (DLMO) is a marker of circadian phase that can be used to appropriately time the administration of bright light or exogenous melatonin in order to elicit a desired phase shift. Determining an individuals circadian phase can be costly and time-consuming. We examined the relationship between the DLMO and sleep times in 16 young healthy individuals who slept at their habitual times for a week. The DLMO occurred about 2 hours before bedtime and 14 hours after wake. Wake time and midpoint of sleep were significantly associated with the DLMO (r = 0.77, r = 0.68 respectively), but bedtime was not (r = 0.36). The possibility of predicting young healthy normally entrained peoples DLMOs from their sleep times is discussed.

A late wake time phase delays the human dim light melatonin rhythm

Short sleep/dark durations, due to late bedtimes or early wake times or both, are common in modern society. We have previously shown that a series of days with a late bedtime phase delays the human dim light melatonin rhythm, as compared to a series of days with an early bedtime, despite a fixed wake time. Here we compared the effect of an early versus late wake time with a fixed bedtime on the human dim light melatonin rhythm. Fourteen healthy subjects experienced 2 weeks of short 6h nights with an early wake time fixed at their habitual weekday wake time and 2 weeks of long 9 h nights with a wake time that occurred 3h later than the early wake time, in counterbalanced order. We found that after 2 weeks with the late wake time, the dim light melatonin onset delayed by 2.4 h and the dim light melatonin offset delayed by 2.6 h (both p < 0.001), as compared to after 2 weeks with the early wake time. These results highlight the substantial influence that wake time, likely via the associated morning light exposure, has on the timing of the human circadian clock. Furthermore, the results suggest that when people truncate their sleep by waking early their circadian clocks phase advance and when people wake late their circadian clocks phase delay.

Early versus late bedtimes phase shift the human dim light melatonin rhythm despite a fixed morning lights on time

Short sleep/dark durations are common in modern society. In a within subjects counterbalanced design, we compared the effect of 7-19 nights with a late bedtime (01:00) versus 7-19 nights with an early bedtime (22:00) on the human dim light melatonin rhythm. All ten healthy subjects experienced lights on time at 07:00 and at least 5 min of outdoor light between 07:00 and 08:00. We found that despite the morning light exposure, the melatonin rhythm following the late bedtime nights was delayed by approximately 0.6 h (P<0.05), as compared to after the early bedtime nights. These results suggest that when people truncate their sleep by delaying their bedtime they also significantly phase delay their circadian rhythms and/or when people advance their bedtime their circadian rhythms advance.