Daily light exposure in morning-type and evening-type individuals

Morning-type individuals (M-types) have earlier sleep schedules than do evening types (E-types) and therefore differ in their exposure to the external light-dark cycle. M-types and E-types usually differ in their endogenous circadian phase as well, but whether this is the cause or the consequence of the difference in light exposure remains controversial. In this study, ambulatory monitoring was used to measure 24-h light exposure in M-type and E-type subjects for 7 consecutive days. The circadian phase of each subject was then estimated in the laboratory using the dim-light melatonin onset in saliva (DLMO) and the core body temperature minimum (Tmin). On average, M-types had earlier sleep schedules and earlier circadian phases than E-types. They also showed more minutes of daily bright light exposure (> 1000 lux) than E-types. As expected, the 24-h patterns of light exposure analyzed in relation to clock time indicated that M-types were exposed to more light in the morning than E-types and that the reverse was true in the late evening. However, there was no significant difference when the light profiles were analyzed in relation to circadian phase, suggesting that, on average, the circadian pacemaker of both M-types and E-types was similarly entrained to the light-dark cycle they usually experience. Some M-types and E-types had different sleep schedules but similar circadian phases. These subjects also had identical light profiles in relation to their circadian phase. By contrast, M-types and E-types with very early or very late circadian phases showed large differences in their profiles of light exposure in relation to their circadian phase. This observation suggests that in these individuals, early or late circadian phases are related to relatively short and long circadian periods and that a phase-delaying profile of light exposure in M-types and a phase-advancing profile in E-types are necessary to ensure a stable entrainment to the 24-h day.     

Older poor-sleeping women display a smaller evening increase in melatonin secretion and lower values of melatonin and core body temperature than good sleepers

Melatonin concentration and core body temperature (CBT) follow endogenous circadian biological rhythms. In the evening, melatonin level increases and CBT decreases. These changes are involved in the regulation of the sleep-wake cycle. Therefore, the authors hypothesized that age-related changes in these rhythms affect sleep quality in older people. In a cross-sectional study design, 11 older poor-sleeping women (aged 62-72 yrs) and 9 older good-sleeping women (60-82 yrs) were compared with 10 younger good-sleeping women (23-28 yrs). The older groups were matched by age and body mass index. Sleep quality was assessed by the Pittsburgh Sleep Quality Index questionnaire. As an indicator of CBT, oral temperature was measured at 1-h intervals from 17:00 to 24:00?h. At the same time points, saliva samples were collected for determining melatonin levels by enzyme-linked immunosorbent assay (ELISA). The dim light melatonin onset (DLMO), characterizing the onset of melatonin production, was calculated. Evening changes in melatonin and CBT levels were tested by the Friedman test. Group comparisons were performed with independent samples tests. Predictors of sleep-onset latency (SOL) were assessed by regression analysis. Results show that the mean CBT decreased in the evening from 17:00 to 24:00?h in both young women (from 36.57°C to 36.25°C, p < .001) and older women (from 36.58°C to 35.88°C, p < .001), being lowest in the older poor sleepers (p < .05). During the same time period, mean melatonin levels increased in young women (from 16.2 to 54.1 pg/mL, p < .001) and older women (from 10.0 to 23.5 pg/mL, p < .001), being lowest among the older poor sleepers (from 20:00 to 24:00?h, p < .05 vs. young women). Older poor sleepers also showed a smaller increase in melatonin level from 17:00 to 24:00?h than older good sleepers (mean?±?SD: 7.0?±?9.63 pg/mL vs. 15.6?±?24.1 pg/mL, p = .013). Accordingly, the DLMO occurred at similar times in young (20:10?h) and older (19:57?h) good-sleeping women, but was delayed ～50?min in older poor-sleeping women (20:47?h). Older poor sleepers showed a shorter phase angle between DLMO and sleep onset, but a longer phase angle between CBT peak and sleep onset than young good sleepers, whereas older good sleepers had intermediate phase angles (insignificant). Regression analysis showed that the DLMO was a significant predictor of SOL in the older women (R(2)?=?0.64, p < .001), but not in the younger women. This indicates that melatonin production started later in those older women who needed more time to fall asleep. In conclusion, changes in melatonin level and CBT were intact in older poor sleepers in that evening melatonin increased and CBT decreased. However, poor sleepers showed a weaker evening increase in melatonin level, and their DLMO was delayed compared with good sleepers, suggesting that it is not primarily the absolute level of endogenous melatonin, but rather the timing of the circadian rhythm in evening melatonin secretion that might be related to disturbances in the sleep-wake cycle in older people.     

Relationship between dim light melatonin onset and the timing of sleep in sleep onset insomniacs

Sleep and Biological Rhythms - Dim light melatonin onset (DLMO), a phase marker of the circadian system can be estimated from sleep diaries of good sleepers. Previous studies have shown a strong...     

Molecular components and mechanism of adrenergic signal transduction in mammalian pineal gland: regulation of melatonin synthesis

Rhythmic neural outputs from the hypothalamic suprachiasmatic nucleus (SCN), which programme the rhythmic release of norepinephrine (NE) from intrapineal nerve fibers, regulate circadian rhythm of melatonin synthesis. Increased secretion of NE with the onset of darkness during the first half of night stimulates melatonin synthesis by several folds. NE binds to both alpha1- and beta-adrenergic receptors present on the pinealocyte membrane and initiates adrenergic signal transduction via cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) generating pathways. The NE-induced adrenergic signal transduction switches 'on' melatonin synthesis during the early hours of night by stimulating expression of the rate-limiting enzyme of melatonin synthesis, N-acetyltransferase (AA-NAT) via cAMP-protein kinase A (PKA)-cAMP response element binding protein (CREB)-cAMP response element (CRE) pathway as well as by increasing AA-NAT activity via cAMP-PKA-14-3-3 protein pathway. Simultaneously, adrenergically-induced expression of inducible cAMP early repressor (ICER) negatively regulates aa-nat gene expression and controls the amplitude of melatonin rhythm. In the second half of night, increased release of acetylcholine from central pinealopetal projections, inhibition of NE secretion by SCN, withdrawal of adrenergic inputs and reversal of events that took place in the first half lead to switching 'off' of melatonin synthesis. Adrenergic signal transduction via cGMP-protein kinase G (PKG)-mitogen activated protein kinase (MAPK)-ribosomal S6 kinase (RSK) pathway also seems to be fully functional, but its role in modulation of melatonin synthesis remains unexplored. This article gives a critical review of information available on various components of the adrenergic signal transduction cascades involved in the regulation of melatonin synthesis.     

Older Poor-Sleeping Women Display a Smaller Evening Increase in Melatonin Secretion and Lower Values of Melatonin and Core Body Temperature Than Good Sleepers

Melatonin concentration and core body temperature (CBT) follow endogenous circadian biological rhythms. In the evening, melatonin level increases and CBT decreases. These changes are involved in the regulation of the sleep-wake cycle. Therefore, the authors hypothesized that age-related changes in these rhythms affect sleep quality in older people. In a cross-sectional study design, 11 older poor-sleeping women (aged 62–72 yrs) and 9 older good-sleeping women (60–82 yrs) were compared with 10 younger good-sleeping women (23–28 yrs). The older groups were matched by age and body mass index. Sleep quality was assessed by the Pittsburgh Sleep Quality Index questionnaire. As an indicator of CBT, oral temperature was measured at 1-h intervals from 17:00 to 24:00?h. At the same time points, saliva samples were collected for determining melatonin levels by enzyme-linked immunosorbent assay (ELISA). The dim light melatonin onset (DLMO), characterizing the onset of melatonin production, was calculated. Evening changes in melatonin and CBT levels were tested by the Friedman test. Group comparisons were performed with independent samples tests. Predictors of sleep-onset latency (SOL) were assessed by regression analysis. Results show that the mean CBT decreased in the evening from 17:00 to 24:00?h in both young women (from 36.57°C to 36.25°C, p < .001) and older women (from 36.58°C to 35.88°C, p < .001), being lowest in the older poor sleepers (p < .05). During the same time period, mean melatonin levels increased in young women (from 16.2 to 54.1 pg/mL, p < .001) and older women (from 10.0 to 23.5 pg/mL, p < .001), being lowest among the older poor sleepers (from 20:00 to 24:00?h, p < .05 vs. young women). Older poor sleepers also showed a smaller increase in melatonin level from 17:00 to 24:00?h than older good sleepers (mean?±?SD: 7.0?±?9.63 pg/mL vs. 15.6?±?24.1 pg/mL, p = .013). Accordingly, the DLMO occurred at similar times in young (20:10?h) and older (19:57?h) good-sleeping women, but was delayed ～50?min in older poor-sleeping women (20:47?h). Older poor sleepers showed a shorter phase angle between DLMO and sleep onset, but a longer phase angle between CBT peak and sleep onset than young good sleepers, whereas older good sleepers had intermediate phase angles (insignificant). Regression analysis showed that the DLMO was a significant predictor of SOL in the older women (R²?=?0.64, p < .001), but not in the younger women. This indicates that melatonin production started later in those older women who needed more time to fall asleep. In conclusion, changes in melatonin level and CBT were intact in older poor sleepers in that evening melatonin increased and CBT decreased. However, poor sleepers showed a weaker evening increase in melatonin level, and their DLMO was delayed compared with good sleepers, suggesting that it is not primarily the absolute level of endogenous melatonin, but rather the timing of the circadian rhythm in evening melatonin secretion that might be related to disturbances in the sleep-wake cycle in older people. (Author correspondence: mdittmar@zoologie.uni-kiel.de)     

Phase shifts in the circadian rhythm in plasma concentrations of melatonin in rams induced by a 1-hour light pulse

The effect of a 1-hr light pulse, given at night, on the timing of the circadian rhythm in the plasma concentration of melatonin was examined in Soay rams to investigate the mechanisms involved in determining the duration of the nocturnal peak in melatonin secretion. Animals (n = 8) were housed under short days (LD 8:16) or long days (LD 16:8) and received a light pulse at various times of night. They were released into constant dim red light (DD) on day 1. Blood samples were collected hourly for 30 hr from 1000 hr on day 3, and the plasma concentration of melatonin was determined by radioimmunoassay to assess the timing of the melatonin peak. Control animals (n = 8) were maintained under the same conditions but received no light pulse. Under short days, a light pulse given early in the night caused a phase delay in the melatonin peak, and a light pulse given in the late night caused a phase advance. The mean duration of the melatonin peak was slightly reduced following a light pulse in the early or late night, and slightly increased following a pulse given near the middle of the night. Under long days, both light-pulse treatments given at night caused a phase delay in the melatonin peak, but there was no significant change in duration of the melatonin peak. The duration of the melatonin peak at day 3 under DD in the control animals was similar for all treatments, regardless of the previous entraining photoperiod (mean duration: 12.6-14.8 hr) and was similar to that under short days (14.6 hr), but was significantly longer than that under long days (8.2 hr). Information on the phase response curve in the Soay ram and on the period of the circadian oscillator governing the melatonin rhythm (c 23.0 hr under DD) predicts a close phase relationship between the end of the light phase and the onset of the melatonin peak as observed under normal 24-hr LD cycles. The current results also indicate that light acts to entrain the circadian rhythm influencing the onset and offset of melatonin secretion, and thus dictates the duration of the melatonin peak.     

Avian Melatonin Synthesis: Photic and Circadian Regulation of Serotonin N-Acetyltransferase mRNA in the Chicken Pineal Gland and Retina

Abstract: The circadian rhythms in melatonin production in the chicken pineal gland and retina reflect changes in the activity of serotonin N -acetyltransferase (arylalkylamine N -acetyltransferase; AA-NAT; EC 2.3.1.87). Here we determined that the chicken AA-NAT mRNA is detectable in follicular pineal cells and retinal photoreceptors and that it exhibits a circadian rhythm, with peak levels at night. AA-NAT mRNA was not detected in other tissues. The AA-NAT mRNA rhythm in the pineal gland and retina persists in constant darkness (DD) and constant lighting (LL). The amplitude of the pineal mRNA rhythm is not decreased in LL. Light appears to influence the phase of the clock driving the rhythm in pineal AA-NAT mRNA in two ways: The peak is delayed by ∼6 h in LL, and it is advanced by >4 h by a 6-h light pulse late in subjective night in DD. Nocturnal AA-NAT mRNA levels do not change during a 20-min exposure to light, whereas this treatment dramatically decreases AA-NAT activity. These observations suggest that the rhythmic changes in chicken pineal AA-NAT activity reflect, at least in part, clock-generated changes in mRNA levels. In contrast, changes in mRNA content are not involved in the rapid light-induced decrease in AA-NAT activity.     

Chick pineal melatonin synthesis: light and cyclic AMP control abundance of serotonin N-acetyltransferase protein

Melatonin production in the pineal gland is high at night and low during the day. This rhythm reflects circadian changes in the activity of serotonin N-acetyltransferase [arylalkylamine N-acetyltransferase (AA-NAT); EC 2.3.1.87], the penultimate enzyme in melatonin synthesis. The rhythm is generated by an endogenous circadian clock. In the chick, a clock is located in the pinealocyte, which also contains two phototransduction systems. One controls melatonin production by adjusting the clock and the other acts distal to the clock, via cyclic AMP mechanisms, to switch melatonin synthesis on and off. Unlike the clock in these cells, cyclic AMP does not appear to regulate activity by altering AA-NAT mRNA levels. The major changes in AA-NAT mRNA levels induced by the clock seemed likely (but not certain) to generate comparable changes in AA-NAT protein levels and AA-NAT activity. Cyclic AMP might also regulate AA-NAT activity via changes in protein levels, or it might act via other mechanisms, including posttranslational changes affecting activity. We measured AA-NAT protein levels and enzyme activity in cultured chick pineal cells and found that they correlated well under all conditions. They rose and fell spontaneously with a circadian rhythm. They also rose in response to agents that increase cyclic AMP. They were raised by agents that increase cyclic AMP, such as forskolin, and lowered by agents that decrease cyclic AMP, such as light and norepinephrine. Thus, both the clock and cyclic AMP can control AA-NAT activity by altering the total amount of AA-NAT protein. Effects of proteosomal proteolysis inhibitors suggest that changes in AA-NAT protein levels, in turn, reflect changes in the rate at which the protein is destroyed by proteosomal proteolysis. It is likely that cyclic AMP-induced changes in AA-NAT protein levels mediate rapid changes in chick pineal AA-NAT activity. Our results indicate that light can rapidly regulate the abundance of a specific protein (AA-NAT) within a photoreceptive cell.     

A compromise phase position for permanent night shift workers: circadian phase after two night shifts with scheduled sleep and light/dark exposure

Night shift work is associated with a myriad of health and safety risks. Phase-shifting the circadian clock such that it is more aligned with night work and day sleep is one way to attenuate these risks. However, workers will not be satisfied with complete adaptation to night work if it leaves them misaligned during days off. Therefore, the goal of this set of studies is to produce a compromise phase position in which individuals working night shifts delay their circadian clocks to a position that is more compatible with nighttime work and daytime sleep yet is not incompatible with late nighttime sleep on days off. This is the first in the set of studies describing the magnitude of circadian phase delays that occurs on progressively later days within a series of night shifts interspersed with days off. The series will be ended on various days in order to take a "snapshot" of circadian phase. In this set of studies, subjects sleep from 23:00 to 7:00 h for three weeks. Following this baseline period, there is a series of night shifts (23:00 to 07:00 h) and days off. Experimental subjects receive five 15 min intermittent bright light pulses (approximately 3500 lux; approximately 1100 microW/cm2) once per hour during the night shifts, wear sunglasses that attenuate all visible wavelengths--especially short wavelengths ("blue-blockers")--while traveling home after the shifts, and sleep in the dark (08:30-15:30 h) after each night shift. Control subjects remain in typical dim room light (<50 lux) throughout the night shift, wear sunglasses that do not attenuate as much light, and sleep whenever they want after the night shifts. Circadian phase is determined from the circadian rhythm of melatonin collected during a dim light phase assessment at the beginning and end of each study. The sleepiest time of day, approximated by the body temperature minimum (Tmin), is estimated by adding 7 h to the dim light melatonin onset. In this first study, circadian phase was measured after two night shifts and day sleep periods. The Tmin of the experimental subjects (n=11) was 04:24+/-0.8 h (mean+/-SD) at baseline and 7:36+/-1.4 h after the night shifts. Thus, after two night shifts, the Tmin had not yet delayed into the daytime sleep period, which began at 08:30 h. The Tmin of the control subjects (n=12) was 04:00+/-1.2 h at baseline and drifted to 4:36+/-1.4 h after the night shifts. Thus, two night shifts with a practical pattern of intermittent bright light, the wearing of sunglasses on the way home from night shifts, and a regular sleep period early in the daytime, phase delayed the circadian clock toward the desired compromise phase position for permanent night shift workers. Additional night shifts with bright light pulses and daytime sleep in the dark are expected to displace the sleepiest time of day into the daytime sleep period, improving both nighttime alertness and daytime sleep but not precluding adequate sleep on days off.     

Familial advanced sleep-phase syndrome: A short-period circadian rhythm variant in humans.

Biological circadian clocks oscillate with an approximately 24-hour period, are ubiquitous, and presumably confer a selective advantage by anticipating the transitions between day and night. The circadian rhythms of sleep, melatonin secretion and body core temperature are thought to be generated by the suprachiasmatic nucleus of the hypothalamus, the anatomic locus of the mammalian circadian clock. Autosomal semi-dominant mutations in rodents with fast or slow biological clocks (that is, short or long endogenous period lengths; tau) are associated with phase-advanced or delayed sleep-wake rhythms, respectively. These models predict the existence of familial human circadian rhythm variants but none of the human circadian rhythm disorders are known to have a familial tendency. Although a slight 'morning lark' tendency is common, individuals with a large and disabling sleep phase-advance are rare. This disorder, advanced sleep-phase syndrome, is characterized by very early sleep onset and offset; only two cases are reported in young adults. Here we describe three kindreds with a profound phase advance of the sleep-wake, melatonin and temperature rhythms associated with a very short tau. The trait segregates as an autosomal dominant with high penetrance. These kindreds represent a well-characterized familial circadian rhythm variant in humans and provide a unique opportunity for genetic analysis of human circadian physiology.     

Hypersensitivity of melatonin suppression in response to light in patients with delayed sleep phase syndrome

Patients with delayed sleep phase syndrome (DSPS) experience a chronic mismatch between the usual daily schedule required by the individual's environment and their circadian sleep-wake pattern, resulting in major academic, work, and social problems. Although functional abnormalities of the circadian pacemaker system have been reported in patients with DSPS, the etiology of DSPS has not been fully elucidated. One hypothesis proposed to explain why patients with DSPS fail to synchronize their 24h sleep-wake cycle to their environment is that they might have reduced sensitivity to environmental time cues, most notably light-dark cycles. Therefore, we compared the sensitivity of melatonin suppression in response to light in patients with DSPS and normal control subjects. Fifteen patients with DSPS and age- and sex-matched healthy controls were studied. As the melatonin secretion rhythm in patients with DSPS was expected to be delayed compared to the controls, the time of peak melatonin secretion was determined in each subject in the first session. In the second session, each subject was exposed to light with an intensity of 1000 lux for 2h beginning 2h prior to his or her peak melatonin secretion. Melatonin was measured by radioimmunoassay in saliva sampled every 30 minutes during the period of light exposure. Suppression of the melatonin concentration in saliva was dependent on duration of light exposure. In addition, the suppressive effect of light on the melatonin concentration was significantly greater in patients with DSPS than in control subjects. The results suggest hypersensitivity to nighttime light exposure in patients with this syndrome. Our findings therefore suggest that evening light restriction is important for preventing patients with DSPS from developing a sleep phase delay. (Chronobiology International, 18(2), 263-271, 2001)     

Melatonin entrains free-running blind people according to a physiological dose-response curve

The specific circadian role proposed for endogenous melatonin production was based on a study of sighted people who took low pharmacological doses (500 µg) of this chemical signal for the “biological night”: the magnitude and direction of the induced phase shifts were dependent on what time of day exogenous melatonin was administered and were described by a phase-response curve that turned out to be the opposite of that for light. We now report that lower (physiological) doses of up to 300 µg can entrain (synchronize) free-running circadian rhythms of 10 totally blind subjects that would otherwise drift later each day. The resulting log-linear dose-response curve in the physiological range adds support for a circadian function of endogenous melatonin in humans. Efficacy of exogenous doses in the physiological range are of clinical significance for totally blind people who will need to take melatonin daily over their entire lifetimes in order to remain entrained to the 24 h day. Left untreated, their free-running endocrine, metabolic, behavioral, and sleep/wake cycles can be almost as burdensome as not having vision.     

Expression of melatonin synthesis genes is controlled by a circadian clock in the pike pineal organ but not in the trout

The photosensitive teleost pineal organ exhibits a daily rhythm in melatonin production. In most teleosts, including the pike, this is driven by an endogenous pineal clock. An exception is the trout, in which the pineal melatonin rhythm is a direct response to darkness. This fundamental difference in the regulation of melatonin production in two closely related species provides investigators a novel opportunity to study the molecular mechanisms of vertebrate clock function. We have studied the circadian regulation of mRNA encoding two melatonin synthesis enzymes by Northern blot analysis. These two enzymes are serotonin N-acetyltransferase (AA-NAT), the penultimate enzyme in melatonin synthesis, and tryptophan hydroxylase (TPH), the first enzyme in melatonin synthesis. A clock controls expression of both AA-NAT and TPH mRNAs in the pineal organ of pike, but not that of trout, in which the levels of these mRNAs are tonically elevated. A parsimoneous explanation of this is that a single circadian system regulates the expression of both AA-NAT and TPH genes in most teleosts, and that in trout this system has been disrupted, perhaps by a single mutation.     

A Compromise Phase Position for Permanent Night Shift Workers: Circadian Phase after Two Night Shifts with Scheduled Sleep and Light/Dark Exposure

Night shift work is associated with a myriad of health and safety risks. Phase‐shifting the circadian clock such that it is more aligned with night work and day sleep is one way to attenuate these risks. However, workers will not be satisfied with complete adaptation to night work if it leaves them misaligned during days off. Therefore, the goal of this set of studies is to produce a compromise phase position in which individuals working night shifts delay their circadian clocks to a position that is more compatible with nighttime work and daytime sleep yet is not incompatible with late nighttime sleep on days off. This is the first in the set of studies describing the magnitude of circadian phase delays that occurs on progressively later days within a series of night shifts interspersed with days off. The series will be ended on various days in order to take a “snapshot” of circadian phase. In this set of studies, subjects sleep from 23:00 to 7:00 h for three weeks. Following this baseline period, there is a series of night shifts (23:00 to 07:00 h) and days off. Experimental subjects receive five 15 min intermittent bright light pulses (～3500 lux; ～1100 µW/cm²) once per hour during the night shifts, wear sunglasses that attenuate all visible wavelengths—especially short wavelengths (“blue‐blockers”)—while traveling home after the shifts, and sleep in the dark (08:30–15:30 h) after each night shift. Control subjects remain in typical dim room light (<50 lux) throughout the night shift, wear sunglasses that do not attenuate as much light, and sleep whenever they want after the night shifts. Circadian phase is determined from the circadian rhythm of melatonin collected during a dim light phase assessment at the beginning and end of each study. The sleepiest time of day, approximated by the body temperature minimum (T_min), is estimated by adding 7 h to the dim light melatonin onset. In this first study, circadian phase was measured after two night shifts and day sleep periods. The T_min of the experimental subjects (n=11) was 04:24±0.8 h (mean±SD) at baseline and 7:36±1.4 h after the night shifts. Thus, after two night shifts, the T_min had not yet delayed into the daytime sleep period, which began at 08:30 h. The T_min of the control subjects (n=12) was 04:00±1.2 h at baseline and drifted to 4:36±1.4 h after the night shifts. Thus, two night shifts with a practical pattern of intermittent bright light, the wearing of sunglasses on the way home from night shifts, and a regular sleep period early in the daytime, phase delayed the circadian clock toward the desired compromise phase position for permanent night shift workers. Additional night shifts with bright light pulses and daytime sleep in the dark are expected to displace the sleepiest time of day into the daytime sleep period, improving both nighttime alertness and daytime sleep but not precluding adequate sleep on days off.     

Exercise elicits phase shifts and acute alterations of melatonin that vary with circadian phase

To examine the immediate phase-shifting effects of high-intensity exercise of a practical duration (1 h) on human circadian phase, five groups of healthy men 20-30 yr of age participated in studies involving no exercise or exposure to morning, afternoon, evening, or nocturnal exercise. Except during scheduled sleep/dark and exercise periods, subjects remained under modified constant routine conditions allowing a sleep period and including constant posture, knowledge of clock time, and exposure to dim light intensities averaging (+/-SD) 42 +/- 19 lx. The nocturnal onset of plasma melatonin secretion was used as a marker of circadian phase. A phase response curve was used to summarize the phase-shifting effects of exercise as a function of the timing of exercise. A significant effect of time of day on circadian phase shifts was observed (P < 0.004). Over the interval from the melatonin onset before exercise to the first onset after exercise, circadian phase was significantly advanced in the evening exercise group by 30 +/- 15 min (SE) compared with the phase delays observed in the no-exercise group (-25 +/- 14 min, P < 0.05). Phase shifts in response to evening exercise exposure were attenuated on the second day after exercise exposure and no longer significantly different from phase shifts observed in the absence of exercise. Unanticipated transient elevations of melatonin levels were observed in response to nocturnal exercise and in some evening exercise subjects. Taken together with the results from previous studies in humans and diurnal rodents, the current results suggest that 1) a longer duration of exercise exposure and/or repeated daily exposure to exercise may be necessary for reliable phase-shifting of the human circadian system and that 2) early evening exercise of high intensity may induce phase advances relevant for nonphotic entrainment of the human circadian system.     

Sleep and circadian phase characteristics of adolescent and young adult males in a naturalistic summertime condition

Our aim was to compare the circadian phase characteristics of healthy adolescent and young adult males in a naturalistic summertime condition. A total of 19 adolescents (mean age 15.7 years) and 18 young adults (mean age 24.5 years) with no sleep problems took part in this study. Two-night polysomnographic (PSG) sleep recordings and 24h secretion patterns of urinary 6-sulfatoxymelatonin were monitored in all 37 subjects. Sleep-wake patterns were initially assessed at home using a standard sleep diary. Circadian assessment included the measure of dim light melatonin offset (DLMOff) and the morningness-eveningness (M/E) questionnaire. As expected, compared to young adults, adolescents habitually spent more nocturnal time in bed and spent more time (and percentage) in delta sleep. No difference was found between adolescents and young adults on multiple sleep latency test (MSLT) sleep onset latencies, M/E, melatonin secretion measures (24h total, nighttime, daytime, and night ratio), and DLMOff. For the subjects as a whole, correlational analyses revealed a significant association between the DLMOff and M/E and between both these phase markers and habitual bedtimes, habitual rising times, and melatonin secretion measures (daytime levels and the night ratio). No association was found between phase markers and daytime sleepiness or sleep consolidation parameters such as sleep efficiency or number of microarousals. These results together indicate that adolescents and young adults investigated during summertime showed similar circadian phase characteristics, and that, in these age groups, an evening phase preference is associated with a delayed melatonin secretion pattern and delayed habitual sleep patterns without a decrease in sleep consolidation or vigilance. (Chronobiology International, 17(4), 489-501, 2000)     

SLEEP AND CIRCADIAN PHASE CHARACTERISTICS OF ADOLESCENT AND YOUNG ADULT MALES IN A NATURALISTIC SUMMERTIME CONDITION

Our aim was to compare the circadian phase characteristics of healthy adolescent and young adult males in a naturalistic summertime condition. A total of 19 adolescents (mean age 15.7 years) and 18 young adults (mean age 24.5 years) with no sleep problems took part in this study. Two-night polysomnographic (PSG) sleep recordings and 24h secretion patterns of urinary 6-sulfatoxymelatonin were monitored in all 37 subjects. Sleep-wake patterns were initially assessed at home using a standard sleep diary. Circadian assessment included the measure of dim light melatonin offset (DLMOff) and the morningness-eveningness (M/E) questionnaire. As expected, compared to young adults, adolescents habitually spent more nocturnal time in bed and spent more time (and percentage) in delta sleep. No difference was found between adolescents and young adults on multiple sleep latency test (MSLT) sleep onset latencies, M/E, melatonin secretion measures (24h total, nighttime, daytime, and night ratio), and DLMOff. For the subjects as a whole, correlational analyses revealed a significant association between the DLMOff and M/E and between both these phase markers and habitual bedtimes, habitual rising times, and melatonin secretion measures (daytime levels and the night ratio). No association was found between phase markers and daytime sleepiness or sleep consolidation parameters such as sleep efficiency or number of microarousals. These results together indicate that adolescents and young adults investigated during summertime showed similar circadian phase characteristics, and that, in these age groups, an evening phase preference is associated with a delayed melatonin secretion pattern and delayed habitual sleep patterns without a decrease in sleep consolidation or vigilance. (Chronobiology International, 17(4), 489–501, 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.