Less exposure to daily ambient light in winter increases sensitivity of melatonin to light suppression

This study was carried out to examine the seasonal difference in the magnitude of the suppression of melatonin secretion induced by exposure to light in the late evening. The study was carried out in Akita (39 degrees North, 140 degrees East), in the northern part of Japan, where the duration of sunshine in winter is the shortest. Ten healthy male university students (mean age: 21.9+/-1.2 yrs) volunteered to participate twice in the study in winter (from January to February) and summer (from June to July) 2004. According to Japanese meteorological data, the duration of sunshine in Akita in the winter (50.5 h/month) is approximately one-third of that in summer (159.7 h/month). Beginning one week prior to the start of the experiment, the level of daily ambient light to which each subject was exposed was recorded every minute using a small light sensor that was attached to the subject's wrist. In the first experiment, saliva samples were collected every hour over a period of 24 h in a dark experimental room (<15 lux) to determine peak salivary melatonin concentration. The second experiment was conducted after the first experiment to determine the percentage of melatonin suppression induced by exposure to light. The starting time of exposure to light was set 2 h before the time of peak salivary melatonin concentration detected in the first experiment. The subjects were exposed to light (1000 lux) for 2 h using white fluorescent lamps (4200 K). The percentage of suppression of melatonin by light was calculated on the basis of the melatonin concentration determined before the start of exposure to light. The percentage of suppression of melatonin 2 h after the start of exposure to light was significantly greater in winter (66.6+/-18.4%) than summer (37.2+/-33.2%), p<0.01). The integrated level of daily ambient light from rising time to bedtime in summer was approximately twice that in winter. The results suggest that the increase in suppression of melatonin by light in winter is caused by less exposure to daily ambient light.     

Less Exposure to Daily Ambient Light in Winter Increases Sensitivity of Melatonin to Light Suppression

This study was carried out to examine the seasonal difference in the magnitude of the suppression of melatonin secretion induced by exposure to light in the late evening. The study was carried out in Akita (39° North, 140° East), in the northern part of Japan, where the duration of sunshine in winter is the shortest. Ten healthy male university students (mean age: 21.9±1.2 yrs) volunteered to participate twice in the study in winter (from January to February) and summer (from June to July) 2004. According to Japanese meteorological data, the duration of sunshine in Akita in the winter (50.5 h/month) is approximately one‐third of that in summer (159.7 h/month). Beginning one week prior to the start of the experiment, the level of daily ambient light to which each subject was exposed was recorded every minute using a small light sensor that was attached to the subject's wrist. In the first experiment, saliva samples were collected every hour over a period of 24 h in a dark experimental room (<15 lux) to determine peak salivary melatonin concentration. The second experiment was conducted after the first experiment to determine the percentage of melatonin suppression induced by exposure to light. The starting time of exposure to light was set 2 h before the time of peak salivary melatonin concentration detected in the first experiment. The subjects were exposed to light (1000 lux) for 2 h using white fluorescent lamps (4200 K). The percentage of suppression of melatonin by light was calculated on the basis of the melatonin concentration determined before the start of exposure to light. The percentage of suppression of melatonin 2 h after the start of exposure to light was significantly greater in winter (66.6±18.4%) than summer (37.2±33.2%), p<0.01). The integrated level of daily ambient light from rising time to bedtime in summer was approximately twice that in winter. The results suggest that the increase in suppression of melatonin by light in winter is caused by less exposure to daily ambient light.     

Are modifications of melatonin circadian rhythm in the middle years of life related to habitual patterns of light exposure?

The mechanisms underlying age-related changes in the signal from the biological clock have yet to be determined. The authors sought to determine if the phase advance of circadian melatonin rhythm during the middle years of life is related to different patterns of habitual light exposure. Forty-one healthy subjects between the ages of 22 and 58 y were studied. Habitual light exposure was measured by a wrist monitor for 7 days. Participants underwent a 25-h constant routine. They provided saliva samples every 30 min, and melatonin concentration was determined by radioimmunoassay to assess salivary dim light melatonin onset (S-DLMO(1.3)). Aging was associated with earlier S-DLMO(1.3). Increasing age was not related to the time spent at different light intensities. However, it was associated with lower percentage of light exposure during the night (between 0200-0400, 0600-0700, and 2300-2400 h) and with higher percentage of light exposure in the morning (between 0800-1100 h). Earlier S-DLMO(1.3) was associated with lower percentage of light exposure early on in the night (between 2200-0000, 0000-0100, and 0200-0300 h) as well as in the afternoon (between 1500-1600 h) and with higher percentage of light exposure in the morning (between 0800-1100 h). When the effects of age were controlled, there was no significant relationship between S-DLMO(1.3) and percentages of light exposure. Yet increasing age was associated with earlier S-DLMO(1.3) regardless of light exposure patterns. Earlier habitual wake time explained the earlier light exposure patterns of older subjects. Both habitual wake time and age contributed to the prediction of S-DLMO(1.3). The results suggest a phase advance of circadian rhythms in the middle years of life. Whereas a clear change in habitual light exposure patterns was associated with aging and with shifts in S-DLMO(1.3), it did not explain entirely the age-related advance of melatonin circadian phase.     

Inferior retinal light exposure is more effective than superior retinal exposure in suppressing melatonin in humans

Illumination of different areas of the human retina elicits differences in acute light-induced suppression of melatonin. The aim of this study was to compare changes in plasma melatonin levels when light exposures of equal illuminance and equal photon dose were administered to superior, inferior, and full retinal fields. Nine healthy subjects participated in the study. Plexiglass eye shields were modified to permit selective exposure of the superior and inferior halves of the retinas of each subject. The Humphrey Visual Field Analyzer was used both to confirm intact full visual fields and to quantify exposure of upper and lower visual fields. On study nights, eyes were dilated, and subjects were exposed to patternless white light for 90 min between 0200 and 0330 under five conditions: (1) full retinal exposure at 200 lux, (2) full retinal exposure at 100 lux, (3) inferior retinal exposure at 200 lux, (4) superior retinal exposure at 200 lux, and (5) a dark-exposed control. Plasma melatonin levels were determined by radioimmunoassay. ANOVA demonstrated a significant effect of exposure condition (F = 5.91, p < 0.005). Post hoc Fisher PLSD tests showed significant (p < 0.05) melatonin suppression of both full retinal exposures as well as the inferior retinal exposure; however, superior retinal exposure was significantly less effective in suppressing melatonin. Furthermore, suppression with superior retinal exposure was not significantly different from that of the dark control condition. The results indicate that the inferior retina contributes more to the light-induced suppression of melatonin than the superior retina at the photon dosages tested in this study. Findings suggest a greater sensitivity or denser distribution of photoreceptors in the inferior retina are involved in light detection for the retinohypothalamic tract of humans.     

Dim light adaptation attenuates acute melatonin suppression in humans

Abstract Studies in rodents with retinal degeneration indicated that neither the rod nor the cone photoreceptors obligatorily participate in circadian responses to light, including melatonin suppression and photoperiodic response. Yet there is a residual phase-shifting response in melanopsin knockout mice, which suggests an alternate or redundant means for light input to the SCN of the hypothalamus. The findings of Aggelopoulos and Meissl suggest a complex, dynamic interrelationship between the classic visual photoreceptors and SCN cell sensitivity to light stimuli, relative to various adaptive lighting conditions. These studies raised the possibility that the phototransductive physiology of the retinohypothalamic tract in humans might be modulated by the visual rod and cone photoreceptors. The aim of the following two-part study was to test the hypothesis that dim light adaptation will dampen the subsequent suppression of melatonin by monochromatic light in healthy human subjects. Each experiment included 5 female and 3 male human subjects between the ages of 18 and 30 years, with normal color vision. Dim white light and darkness adaptation exposures occurred between midnight and 0200 h, and a full-field 460-nm light exposure subsequently occurred between 0200 and 0330-h for each adaptation condition, at 2 different intensities. Plasma samples were drawn following the 2-h adaptation, as well as after the 460-nm monochromatic light exposure, and melatonin was measured by radioimmunoassay. Comparison of melatonin suppression responses to monochromatic light in both studies revealed a loss of significant suppression after dim white light adaptation compared with dark adaptation (p < 0.04 and p < 0.01). These findings indicate that the activity of the novel circadian photoreceptive system in humans is subject to subthreshold modulation of its sensitivity to subsequent monochromatic light exposure, varying with the conditions of light adaptation prior to exposure.     

Effectiveness of a red-visor cap for preventing light-induced melatonin suppression during simulated night work

Bright light at night improves the alertness of night workers. Melatonin suppression induced by light at night is, however, reported to be a possible risk factor for breast cancer. Short-wavelength light has a strong impact on melatonin suppression. A red-visor cap can cut the short-wavelength light from the upper visual field selectively with no adverse effects on visibility. The purpose of this study was to investigate the effects of a red-visor cap on light-induced melatonin suppression, performance, and sleepiness at night. Eleven healthy young male adults (mean age: 21.2±0.9 yr) volunteered to participate in this study. On the first day, the subjects spent time in dim light (<15 lx) from 20:00 to 03:00 to measure baseline data of nocturnal salivary melatonin concentration. On the second day, the subjects were exposed to light for four hours from 23:00 to 03:00 with a nonvisor cap (500 lx), red-visor cap (approx. 160 lx) and blue-visor cap (approx. 160 lx). Subjective sleepiness and performance of a psychomotor vigilance task (PVT) were also measured on the second day. Compared to salivary melatonin concentration under dim light, the decrease in melatonin concentration was significant in a nonvisor cap condition but was not significant in a red-visor cap condition. The percentages of melatonin suppression in the nonvisor cap and red-visor cap conditions at 4 hours after exposure to light were 52.6±22.4% and 7.7±3.3%, respectively. The red-visor cap had no adverse effect on performance of the PVT, brightness and visual comfort, though it tended to increase subjective sleepiness. These results suggest that a red-visor cap is effective in preventing melatonin suppression with no adverse effects on vigilance performance, brightness and visibility.     

Influence of eye colors of Caucasians and Asians on suppression of melatonin secretion by light

This experiment tested effects of human eye pigmentation depending on the ethnicity on suppression of nocturnal melatonin secretion by light. Ten healthy Caucasian males with blue, green, or light brown irises (light-eyed Caucasians) and 11 Asian males with dark brown irises (dark-eyed Asians) volunteered to participate in the study. The mean ages of the light-eyed Caucasians and dark-eyed Asians were 26.4 +/- 3.2 and 25.3 +/- 5.7 years, respectively. The subjects were exposed to light (1,000 lux) for 2 h at night. The starting time of exposure was set to 2 h before the time of peak salivary melatonin concentration of each subject, which was determined in a preliminary experiment. Salivary melatonin concentration and pupil size were measured before exposure to light and during exposure to light. The percentage of suppression of melatonin secretion by light was calculated. The percentage of suppression of melatonin secretion 2 h after the start of light exposure was significantly larger in light-eyed Caucasians (88.9 +/- 4.2%) than in dark-eyed Asians (73.4 +/- 20.0%) (P < 0.01). No significant difference was found between pupil sizes in light-eyed Caucasians and dark-eyed Asians. These results suggest that sensitivity of melatonin to light suppression is influenced by eye pigmentation and/or ethnicity.     

Effects of television luminance and wavelength at habitual bedtime on melatonin and cortisol secretion in humans

Sleep and Biological Rhythms - The aim of this study was to examine the effect of exposure to different types of television displays at habitual bedtime on human melatonin and cortisol secretion....     

Nocturnal increase in plasma cGMP levels in humans.

The circadian dynamics of responses to cyclic guanosine 3',5'-monophosphate (cGMP) in in vitro experiments and the stimulating effects of the pineal hormone melatonin on cGMP levels both in vitro and in vivo provoked an investigation into the diurnal pattern of occurrence of this second messenger in human plasma and its correlation with plasma melatonin levels. Plasma cGMP levels were measured in 9 normal human subjects who were over 50 years of age. Samples were obtained hourly through a 20-h period (11 a.m. to 7 a.m.) that included the subjects' habitual hours of nocturnal sleep; physical activity was kept to a minimum during the daylight hours. The area under the time-plasma cGMP concentration curve showed a significant increase during the period of nocturnal sleep compared to that observed during the period of daytime wakefulness. The individual temporal pattern of the nocturnal rise in plasma cGMP differed among the subjects; however, the initial increase typically was observed soon after bedtime. No significant correlation was observed between individual nocturnal plasma melatonin levels and cGMP levels.     

Quantal melatonin suppression by exposure to low intensity light in man

Plasma melatonin concentrations were examined following three relatively low intensities of artificial light. Six normal, healthy control subjects were all exposed to (a) 200 lux, (b) 400 lux and (c) 600 lux for a three hour duration from midnight to 0300 h. Blood was also collected on a control night where light intensity was less than 10 lux throughout. Significant suppression of melatonin was observed following light of 400 lux and 600 lux intensity when compared to the control night (p less than 0.05; Mann-Whitney U-test). 200 lux light did not produce a statistically significant melatonin suppression when compared with control samples. Each light intensity produced its own individual maximal melatonin suppression by one hour of exposure. Increased duration of exposure to the light had no further influence on melatonin plasma concentrations. These data confirm a dose response relationship between light and melatonin suppression, and indicate that there is no reciprocal relationship between the effects of light intensity and the duration of exposure on maximal melatonin suppression in man.     

Sensitivity of the human circadian system to short-wavelength (420-nm) light

The circadian and neurobehavioral effects of light are primarily mediated by a retinal ganglion cell photoreceptor in the mammalian eye containing the photopigment melanopsin. Nine action spectrum studies using rodents, monkeys, and humans for these responses indicate peak sensitivities in the blue region of the visible spectrum ranging from 459 to 484 nm, with some disagreement in short-wavelength sensitivity of the spectrum. The aim of this work was to quantify the sensitivity of human volunteers to monochromatic 420-nm light for plasma melatonin suppression. Adult female (n=14) and male (n=12) subjects participated in 2 studies, each employing a within-subjects design. In a fluence-response study, subjects (n=8) were tested with 8 light irradiances at 420 nm ranging over a 4-log unit photon density range of 10(10) to 10(14) photons/cm(2)/sec and 1 dark exposure control night. In the other study, subjects (n=18) completed an experiment comparing melatonin suppression with equal photon doses (1.21 x 10(13) photons/cm(2)/sec) of 420 nm and 460 nm monochromatic light and a dark exposure control night. The first study demonstrated a clear fluence-response relationship between 420-nm light and melatonin suppression (p<0.001) with a half-saturation constant of 2.74 x 10(11) photons/cm(2)/sec. The second study showed that 460-nm light is significantly stronger than 420-nm light for suppressing melatonin (p<0.04). Together, the results clarify the visible short-wavelength sensitivity of the human melatonin suppression action spectrum. This basic physiological finding may be useful for optimizing lighting for therapeutic and other applications.     

Blue light from light-emitting diodes elicits a dose-dependent suppression of melatonin in humans

Light suppresses melatonin in humans, with the strongest response occurring in the short-wavelength portion of the spectrum between 446 and 477 nm that appears blue. Blue monochromatic light has also been shown to be more effective than longer-wavelength light for enhancing alertness. Disturbed circadian rhythms and sleep loss have been described as risk factors for astronauts and NASA ground control workers, as well as civilians. Such disturbances can result in impaired alertness and diminished performance. Prior to exposing subjects to short-wavelength light from light-emitting diodes (LEDs) (peak λ = 469 nm; 1/2 peak bandwidth = 26 nm), the ocular safety exposure to the blue LED light was confirmed by an independent hazard analysis using the American Conference of Governmental Industrial Hygienists exposure limits. Subsequently, a fluence-response curve was developed for plasma melatonin suppression in healthy subjects (n = 8; mean age of 23.9 ± 0.5 years) exposed to a range of irradiances of blue LED light. Subjects with freely reactive pupils were exposed to light between 2:00 and 3:30 AM. Blood samples were collected before and after light exposures and quantified for melatonin. The results demonstrate that increasing irradiances of narrowband blue-appearing light can elicit increasing plasma melatonin suppression in healthy subjects (P < 0.0001). The data were fit to a sigmoidal fluence-response curve (R(2) = 0.99; ED(50) = 14.19 μW/cm(2)). A comparison of mean melatonin suppression with 40 μW/cm(2) from 4,000 K broadband white fluorescent light, currently used in most general lighting fixtures, suggests that narrow bandwidth blue LED light may be stronger than 4,000 K white fluorescent light for suppressing melatonin.     

Melatonin suppression during a simulated night shift in medium intensity light is increased by 10-minute breaks in dim light and decreased by 10-minute breaks in bright light

ABSTRACT

Exposure to light at night results in disruption of endogenous circadian rhythmicity and/or suppression of pineal melatonin, which can consequently lead to acute or chronic adverse health problems. In the present study, we investigated whether exposure to very dim light or very bright light for a short duration influences melatonin suppression, subjective sleepiness, and performance during exposure to constant moderately bright light. Twenty-four healthy male university students were divided into two experimental groups: Half of them (mean age: 20.0 ± 0.9 years) participated in an experiment for short-duration (10 min) light conditions of medium intensity light (430 lx, medium breaks) vs. very dim light (< 1 lx, dim breaks) and the other half (mean age: 21.3 ± 2.5 years) participated in an experiment for short-duration light conditions of medium intensity light (430 lx, medium breaks) vs. very bright light (4700 lx, bright breaks). Each simulated night shift consisting of 5 sets (each including 50-minute night work and 10-minute break) was performed from 01:00 to 06:00 h. The subjects were exposed to medium intensity light (550 lx) during the night work. Each 10-minute break was conducted every hour from 02:00 to 06:00 h. Salivary melatonin concentrations were measured, subjective sleepiness was assessed, the psychomotor vigilance task was performed at hourly intervals from 21:00 h until the end of the experiment. Compared to melatonin suppression between 04:00 and 06:00 h in the condition of medium breaks, the condition of dim breaks significantly promoted melatonin suppression and the condition of bright breaks significantly diminished melatonin suppression. However, there was no remarkable effect of either dim breaks or bright breaks on subjective sleepiness and performance of the psychomotor vigilance task. Our findings suggest that periodic exposure to light for short durations during exposure to a constant light environment affects the sensitivity of pineal melatonin to constant light depending on the difference between light intensities in the two light conditions (i.e., short light exposure vs. constant light exposure). Also, our findings indicate that exposure to light of various intensities at night could be a factor influencing the light-induced melatonin suppression in real night work settings.     

Phase-dependent effect of room light exposure in a 5-h advance of the sleep-wake cycle: implications for jet lag

The acute disruption in sleep quality, vigilance levels, and cognitive and athletic performance observed after transmeridian flights is presumed to be the result of a transient misalignment between the endogenous circadian pacemaker and the shifted sleep schedule. Several laboratory and field experiments have demonstrated that exposure to bright artificial light can accelerate circadian entrainment to a shifted sleep-wake schedule. In the present study, the authors investigated whether the schedule of exposure to indoor room light, to which urban dwellers are typically exposed, can substantially affect circadian adaptation to a simulated eastward voyage. We enrolled 15 healthy young men in a laboratory simulation of a Montreal-to-London voyage. Subjects were exposed to 6 h of room light (mean +/- SD: 379+/-10) prior to bedtime (n = 7) or when on a progressively advancing schedule (n = 8) early in the day. The remaining 10 hours of wakefulness were spent in dim light (4+/-1 lux). Circadian assessments, performed via the constant routine procedure, evaluated the phase of the endogenous circadian rhythms of core body temperature and plasma melatonin before and after 1 week on the shifted schedule. At the end of the study, only subjects exposed to room light on the advancing schedule expressed oscillations of the endogenous circadian pacemaker in phase with the new sleep-wake cycle. In this group, a mean advance shift of the nadir of core body temperature of +5:22+/-0:15 h was observed, with parallel shifts in plasma melatonin concentration and subjective alertness. The circadian rhythms of subjects exposed to room light later in the day remained much more adjusted to the departure than to the destination time zone. These results demonstrate that the schedule of exposure to room light can substantially affect circadian adaptation to a shifted sleep-wake schedule.     

Illuminating the impact of habitual behaviors in depression

Researchers have hypothesized that habitual behaviors are zeitgebers for the circadian clock. However, few studies have examined the relationship between habitual behaviors and light, the strongest zeitgeber. Depression is an ideal model in which to explore this relationship because depression is a disorder associated with disruptions in circadian biological activity, sleep, and social rhythms (or patterns of habitual behaviors). We hypothesized that individuals with fewer habitual behaviors have less average exposure to light from morning rise time to evening bedtime and that a reduction in light exposure increases the likelihood of depression. Thirty-nine depressed and 39 never-depressed participants wore an ambulatory light monitor and completed the Social Rhythm Metric over the course of 2 weeks. Linear and logistic regression techniques were used to calculate regression coefficients, and confidence limits based on the distribution of the product of two normal random variables were computed to test the significance of the mediation effect. Infrequent habitual behaviors were associated with a decrease in average levels of light exposure, and low levels of light increased the likelihood of depression. This mediation effect was partial; the overall number of habitual behaviors had a direct relationship with depression above and beyond the association with light exposure. Longitudinal studies are needed to empirically demonstrate the direction of relationships between each of the variables tested.     

Nocturnal melatonin levels in human volunteers exposed to intermittent 60 Hz magnetic fields

Two double-blind laboratory-based studies were performed to determine whether a suppression of nocturnal melatonin similar to that observed in rodents occurs when humans are exposed to magnetic fields at night. In study 1, 33 men were exposed to sham, 10 mG, or 200 mG intermittent, circularly polarized magnetic fields from 2300 to 0700 h under controlled environmental and exposure test conditions. Overall, exposure had no effect on melatonin levels. Men with preexisting low levels of melatonin, however, showed significantly greater suppression of melatonin when they were exposed to light and also when they were exposed to the 200 mG magnetic-field condition. Study 2 directly tested the hypothesis that low-melatonin subjects show enhanced sensitivity when exposed to light and to 200 mG magnetic fields. After preexposure screening, each of 40 men slept in the exposure facility on two nights. On one night, the men were sham exposed. On the other night, they were exposed to the 200 mG field condition used previously. Again, exposure had no overall effect on melatonin levels. The original finding of enhanced sensitivity in low-melatonin subjects was not replicated in this study. We conclude that the intermittent exposure conditions used in these two studies were not effective in altering nocturnal melatonin release patterns in human volunteers. Further research is underway with regard to exposure parameters, hormonal and immune system measures, and individual differences. © 1996 Wiley-Liss, Inc.     

Seasonal variations of melatonin secretion in young females under natural and artificial light conditions in Fukuoka, Japan

The purpose of this study was to examine the seasonal variations of melatonin secretion of subjects and of their surrounding light conditions. Eight Japanese female students (20.1+/-2.6 yrs, Mean+/-SD) living in Fukuoka, Japan, participated in the present study. Saliva samples were collected every 3 hours over the course of a day, and the light intensity during daily life was measured every 1 min for 5 days in the four seasons. Almost all subjects had different melatonin secretory profiles in autumn, with only two subjects showing similar rhythms in all four seasons. The peak values of melatonin secretion calculated by a spline interpolation were higher in autumn than those in other seasons (p<0.001, Fisher's PLSD) and its peak time in this season was significantly delayed compared with those in spring and summer (p<0.05, Fisher's PLSD). The amount of time during daytime exposure to light of >1,000 lux was at least thirty minutes in all the seasons, and there were no significant differences among them. The relationship between peak level of melatonin secretion and amount of time of daytime light exposure to >1,000 lux was significant only in the autumn. During this season, there was a significant positive correlation (r=0.83, p<0.05, n=6), except for two subjects, whose melatonin secretion remained low.     

Entrainment of Circadian Programs

Circadian rhythms were recently proposed as a measure of physiological state and prognosis in disorders of consciousness (DOC). So far, melatonin regulation was never assessed in vegetative state (VS). Aim of our research was to investigate the nocturnal melatonin levels and light-induced melatonin suppression in a cohort of VS patients. We assessed six consecutive patients (four men, age 33.3?±?9.3 years) with post-traumatic VS and nine age-matched healthy volunteers (five men, age 34.3?±?8.9 years) on two consecutive nights: one baseline and one light exposure night. During baseline, night subjects were in bed in a dim (<5?lux) room from 10?pm to 8?am. Blood samples were collected hourly 00:30–3:30?am (00:30?=?MLT1; 1:30?=?MLT2; 2:30?=?MLT3; and 3:30?=?MLT4). Identical setting was used for melatonin suppression test night, except for the exposure to monochromatic (470?nm) light from 1:30 to 3:30?am. Plasma melatonin levels were evaluated by radioimmunoassay. Magnitude of melatonin suppression was assessed by melatonin suppression score (caMSS) and suppression rate. We searched for group differences in melatonin levels, differences between repeated samples melatonin concentrations during baseline night and light exposure night, and light-induced suppression of melatonin secretion. During baseline night, controls showed an increase of melatonin (MLT4 vs MLT1, p?=?0.037), while no significant changes were observed in VS melatonin levels (p?=?0.172). Baseline night MLT4 was significantly lower in VS vs controls (p?=?0.036). During light-exposure night, controls displayed a significant suppression of melatonin (MLT3 and MLT4 vs MLT2, p?=?0.016 and 0.002, respectively), while VS patients displayed no significant changes. The magnitude of light-induced suppression of melatonin levels was statistically different between groups considering control adjusted caMSS (p?=?0.000), suppression rate (p?=?0.002) and absolute percentage difference (p?=?0.012). These results demonstrate for the first time that VS patients present an alteration in night melatonin secretion and reduced light-induced melatonin suppression. These findings confirm previous studies demonstrating a disruption of the circadian system in DOC and suggest a possible benefit from melatonin supplementation in VS.     

HYPERSENSITIVITY OF MELATONIN SUPPRESSION IN RESPONSE TO LIGHT IN PATIENTS WITH DELAYED SLEEP PHASE SYNDROME*

Patients with delayed sleep phase syndrome (DSPS) experiencea chronic mismatch between the usual daily schedule required by the individual'senvironment and their circadian sleep-wake pattern, resulting in major academic,work, and social problems. Although functional abnormalities of the circadianpacemaker system have been reported in patients with DSPS, the etiology ofDSPS has not been fully elucidated. One hypothesis proposed to explain whypatients with DSPS fail to synchronize their 24h sleep-wake cycle to theirenvironment is that they might have reduced sensitivity to environmental timecues, most notably light-dark cycles. Therefore, we compared the sensitivityof melatonin suppression in response to light in patients with DSPS and normalcontrol subjects. Fifteen patients with DSPS and age- and sex-matched healthycontrols were studied. As the melatonin secretion rhythm in patients withDSPS was expected to be delayed compared to the controls, the time of peakmelatonin secretion was determined in each subject in the first session. Inthe second session, each subject was exposed to light with an intensity of1000 lux for 2h beginning 2h prior to his or her peak melatonin secretion.Melatonin was measured by radioimmunoassay in saliva sampled every 30 minutesduring the period of light exposure. Suppression of the melatonin concentrationin saliva was dependent on duration of light exposure. In addition, the suppressiveeffect of light on the melatonin concentration was significantly greater inpatients with DSPS than in control subjects. The results suggest hypersensitivityto nighttime light exposure in patients with this syndrome. Our findings thereforesuggest that evening light restriction is important for preventing patientswith DSPS from developing a sleep phase delay. (ChronobiologyInternational, 18(2), 263–271, 2001)     

Illuminating the Impact of Habitual Behaviors in Depression

Researchers have hypothesized that habitual behaviors are zeitgebers for the circadian clock. However, few studies have examined the relationship between habitual behaviors and light, the strongest zeitgeber. Depression is an ideal model in which to explore this relationship because depression is a disorder associated with disruptions in circadian biological activity, sleep, and social rhythms (or patterns of habitual behaviors). We hypothesized that individuals with fewer habitual behaviors have less average exposure to light from morning rise time to evening bedtime and that a reduction in light exposure increases the likelihood of depression. Thirty‐nine depressed and 39 never‐depressed participants wore an ambulatory light monitor and completed the Social Rhythm Metric over the course of 2 weeks. Linear and logistic regression techniques were used to calculate regression coefficients, and confidence limits based on the distribution of the product of two normal random variables were computed to test the significance of the mediation effect. Infrequent habitual behaviors were associated with a decrease in average levels of light exposure, and low levels of light increased the likelihood of depression. This mediation effect was partial; the overall number of habitual behaviors had a direct relationship with depression above and beyond the association with light exposure. Longitudinal studies are needed to empirically demonstrate the direction of relationships between each of the variables tested.