Reduced phase-advance of plasma melatonin after bright morning light in the luteal, but not follicular, menstrual cycle phase in premenstrual dysphoric disorder: an extended study

The authors previously observed blunted phase-shift responses to morning bright light in women with premenstrual dysphoric disorder (PMDD). The aim of this study was to determine if these findings could be replicated using a higher-intensity, shorter-duration light pulse and to compare these results with the effects of an evening bright-light pulse. In 17 PMDD patients and 14 normal control (NC) subjects, the authors measured plasma melatonin at 30-min intervals from 18:00 to 10:00 h in dim (<30 lux) or dark conditions the night before (Night 1) and after (Night 3) a bright-light pulse (administered on Night 2) in both follicular and luteal menstrual cycle phases. The bright light (either 3000 lux for 6 h or 6000 lux for 3 h) was given either in the morning (AM light), 7 h after the dim light melatonin onset (DLMO) measured the previous month, or in the evening (PM light), 3 h after the DLMO. In the luteal, but not in the follicular, phase, AM light advanced melatonin offset between Night 1 and Night 3 significantly less in PMDD than in NC subjects. The effects of PM light were not significant, nor were there significant effects of the light pulse on melatonin measures of onset, duration, peak, or area under the curve. These findings replicated the authors' previous finding of a blunted phase-shift response to morning bright light in the luteal, but not the follicular, menstrual cycle phase in PMDD compared with NC women, using a brighter (6000 vs. 3000 lux) light pulse for a shorter duration (3 vs. 6 h). As the effect of PM bright light on melatonin phase-shift responses did not differ between groups or significantly alter other melatonin measures, these results suggest that in PMDD there is a luteal-phase subsensitivity or an increased resistance to morning bright-light cues that are critical in synchronizing human biological rhythms. The resulting circadian rhythm malsynchonization may contribute to the occurrence of luteal phase depressive symptoms in women with PMDD.     

Circadian uses of melatonin in humans

Melatonin in humans can be an independent or dependent variable. Measurement of endogenous melatonin levels under dim-light conditions, particularly the dim-light melatonin onset (DLMO), has received increasing attention among researchers, and for clinicians it may soon become a convenient test that can be done at home using saliva collections in the evening, without interfering with sleep. Melatonin, even at low physiological doses, can cause advances (shifts to an earlier time) or delays (shifts to a later time) depending on when it is administered on its phase-response curve (in most sighted people, these times are approximately in the p.m. and in the a.m., respectively). Although both bright light and melatonin can be used separately or together in the treatment of circadian phase disorders in sighted people-such as advanced and delayed sleep phase syndromes, jet lag, shift-work maladaptation, and winter depression (seasonal affective disorder, or SAD)-melatonin is the treatment of choice in totally blind people. These people provide a unique opportunity to study the human circadian system without the overwhelming effects of ocularly mediated light, thus permitting us to establish that all blind free-runners (BFRs) studied under high resolution appear to have phase-advancing and phase-delaying responses to as yet unidentified zeitgebers (time givers) that are usually too weak to result in entrainment.     

Preliminary evidence that light through the eyelids can suppress melatonin and phase shift dim light melatonin onset

ABSTRACT: BACKGROUND: A previous study reported a method for measuring the spectral transmittance of individual human eyelids. A prototype light mask using narrow-band "green" light (lambdamax = 527 nm) was used to deliver light through closed eyelids in two within-subjects studies. The first study investigated whether an individual-specific light dose could suppress melatonin by 40% through the closed eyelid without disrupting sleep. The light doses were delivered at three times during the night: 1) beginning (while subjects were awake), 2) middle (during rapid eye movement (REM) sleep), and 3) end (during non-REM sleep). The second study investigated whether two individual-specific light doses expected to suppress melatonin by 30% and 60% and delivered through subjects' closed eyelids before the time of their predicted minimum core body temperature would phase delay the timing of their dim light melatonin onset (DLMO). FINDINGS: Compared to a dark control night, light delivered through eyelids suppressed melatonin by 36% (p = 0.01) after 60-minute light exposure at the beginning, 45% (p = 0.01) at the middle, and 56% (p < 0.0001) at the end of the night. In the second study, compared to a dark control night, melatonin was suppressed by 25% (p = 0.03) and by 45% (p = 0.009) and circadian phase, as measured by DLMO, was delayed by 17 minutes (p = 0.03) and 71 minutes (ns) after 60-minute exposures to light levels 1 and 2, respectively. CONCLUSIONS: These studies demonstrate that individual-specific doses of light delivered through closed eyelids can suppress melatonin and phase shift DLMO and may be used to treat circadian sleep disorders.     

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.     

A week of simulated night work delays salivary melatonin onset

In most studies, the magnitude and rate of adaptation to various night work schedules is assessed using core body temperature as the marker of circadian phase. The aim of the current study was to assess adaptation to a simulated night work schedule using salivary dim light melatonin onset (DLMO) as an alternative circadian phase marker. It was hypothesised that the night work schedule would result in a phase delay, manifest in relatively later DLMO, but that this delay would be somewhat inhibited by exposure to natural light. Participants worked seven consecutive simulated 8-hour night shifts (23:00-07:00 h). By night 7, there was a mean cumulative phase delay of 5.5 hours, equivalent to an average delay of 0.8 hours per day. This indicates that partial circadian adaptation occurred in response to the simulated night work schedule. The radioimmunoassay used in the current study provides a sensitive assessment of melatonin concentration in saliva that can be used to determine DLMO, and thus provides an alternative phase marker to core body temperature, at least in laboratory studies.     

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.     

The hockey-stick method to estimate evening dim light melatonin onset (DLMO) in humans

The onset of melatonin secretion in the evening is the most reliable and most widely used index of circadian timing in humans. Saliva (or plasma) is usually sampled every 0.5–1 hours under dim-light conditions in the evening 5–6 hours before usual bedtime to assess the dim-light melatonin onset (DLMO). For many years, attempts have been made to find a reliable objective determination of melatonin onset time either by fixed or dynamic threshold approaches. The here-developed hockey-stick algorithm, used as an interactive computer-based approach, fits the evening melatonin profile by a piecewise linear-parabolic function represented as a straight line switching to the branch of a parabola. The switch point is considered to reliably estimate melatonin rise time. We applied the hockey-stick method to 109 half-hourly melatonin profiles to assess the DLMOs and compared these estimates to visual ratings from three experts in the field. The DLMOs of 103 profiles were considered to be clearly quantifiable. The hockey-stick DLMO estimates were on average 4 minutes earlier than the experts' estimates, with a range of ?27 to +13 minutes; in 47% of the cases the difference fell within ±5 minutes, in 98% within ?20 to +13 minutes. The raters' and hockey-stick estimates showed poor accordance with DLMOs defined by threshold methods. Thus, the hockey-stick algorithm is a reliable objective method to estimate melatonin rise time, which does not depend on a threshold value and is free from errors arising from differences in subjective circadian phase estimates. The method is available as a computerized program that can be easily used in research settings and clinical practice either for salivary or plasma melatonin values.     

Sleep logs of young adults with self-selected sleep times predict the dim light melatonin onset

The purpose of this study was to determine whether a sleep log parameter could be used to estimate the circadian phase of normal, healthy, young adults who sleep at their normal times, and thus naturally have day-to-day variability in their times of sleep. Thus, we did not impose any restrictions on the sleep schedules of our subjects (n = 26). For 14 d, they completed daily sleep logs that were verified with wrist activity monitors. On day 14, salivary melatonin was sampled every 30 min in dim light from 19:00 to 07:30 h to determine the dim light melatonin onset (DLMO). Daily sleep parameters (onset, midpoint, and wake) were taken from sleep logs and averaged over the last 5, 7, and 14 d before determination of the DLMO. The mean DLMO was 22:48 +/- 01:30 h. Sleep onset and wake time averaged over the last 5 d were 01:44 +/- 01:41 and 08:44 +/- 01:26 h, respectively. The DLMO was significantly correlated with sleep onset, midpoint, and wake time, but was most strongly correlated with the mean midpoint of sleep from the last 5 d (r = 0.89). The DLMO predicted using the mean midpoint of sleep from the last 5 d was within 1 h of the DLMO determined from salivary melatonin for 92% of the subjects; in no case did the difference exceed 1.5 h. The correlation between the DLMO and the score on the morningness-eveningness questionnaire was significant but comparatively weak (r = -0.48). We conclude that the circadian phase of normal, healthy day-active young adults can be accurately predicted using sleep times recorded on sleep logs (and verified by actigraphy), even when the sleep schedules are irregular.     

The endogenous melatonin profile as a marker for circadian phase position.

Several circadian rhythms have been used to assess the phase of the endogenous circadian pacemaker (ECP). However, when more than one marker rhythm is measured, results do not always agree. Questions then inevitably arise. Are there multiple oscillators? Are some markers more reliable than others? Masking is a problem for all marker rhythms. Masking of melatonin is minimized by sampling under dim light. The dim-light melatonin onset (DLMO) is particularly convenient since it can usually be obtained before sleep. However, assessing the DLMO in low melatonin producers may be problematic, particularly with the commonly used operationally defined threshold of 10 pg/ml. This study evaluates various circadian phase markers provided by the plasma melatonin profile in 14 individuals, several of whom are low melatonin producers. The amount (amplitude) of melatonin production appears to influence the phase of many points on the melatonin profile. Accordingly, when low producers are in a data set, we now prefer a lower DLMO threshold than the one previously recommended (10 pg/ml). Indeed, there are some low producers who never exceed this threshold at any time. Radioimmunoassays are now available that have the requisite sensitivity and specificity to support the use of a lower threshold. Nevertheless, the dim-light melatonin offset (DLMOff), even when operationally defined at thresholds less than 10 pg/ml, appears to be confounded by amplitude in this study; in such cases, it may be preferable to use the melatonin synthesis offset (SynOff) because it is not confounded by amplitude and because, theoretically, it is temporally closer to the endogenous mechanism signaling the offset of production. The question of whether the termination mechanism of melatonin synthesis is related to an interval timer or to a second oscillator loosely coupled to the onset oscillator is probably best answered using the SynOff rather than the DLMOff. It is hoped that these findings will make a useful contribution to the debate on the best ways to use points on the melatonin profile to assess circadian phase position in humans.     

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...     

Daily exercise facilitates phase delays of circadian melatonin rhythm in very dim light

Shift workers and transmeridian travelers are exposed to abnormal work-rest cycles, inducing a change in the phase relationship between the sleep-wake cycle and the endogenous circadian timing system. Misalignment of circadian phase is associated with sleep disruption and deterioration of alertness and cognitive performance. Exercise has been investigated as a behavioral countermeasure to facilitate circadian adaptation. In contrast to previous studies where results might have been confounded by ambient light exposure, this investigation was conducted under strictly controlled very dim light (standing approximately 0.65 lux; angle of gaze) conditions to minimize the phase-resetting effects of light. Eighteen young, fit males completed a 15-day randomized clinical trial in which circadian phase was measured in a constant routine before and after exposure to a week of nightly bouts of exercise or a nonexercise control condition after a 9-h delay in the sleep-wake schedule. Plasma samples collected every 30-60 min were analyzed for melatonin to determine circadian phase. Subjects who completed three 45-min bouts of cycle ergometry each night showed a significantly greater shift in the dim light melatonin onset (DLMO(25%)), dim light melatonin offset, and midpoint of the melatonin profile compared with nonexercising controls (Student t-test; P < 0.05). The magnitude of phase delay induced by the exercise intervention was significantly dependent on the relative timing of the exercise after the preintervention DLMO(25%) (r = -0.73, P < 0.05) such that the closer to the DLMO(25%), the greater the phase shift. These data suggest that exercise may help to facilitate circadian adaptation to schedules requiring a delay in the sleep-wake cycle.     

Morning melatonin has limited benefit as a soporific for daytime sleep after night work

Exogenous melatonin administration in humans is known to exert both chronobiotic (phase shifting) and soporific effects. In a previous study in our lab, young, healthy, subjects worked five consecutive simulated night shifts (23:00 to 07:00 h) and slept during the day (08:30 to 15:30 h). Large phase delays of various magnitudes were produced by the study interventions, which included bright light exposure during the night shifts, as assessed by the dim light melatonin onset (DLMO) before (baseline) and after (final) the five night shifts. Subjects also ingested either 1.8 mg sustained-release melatonin or placebo before daytime sleep. Although melatonin at this time should delay the circadian clock, this previous study found that it did not increase the magnitude of phase delays. To determine whether melatonin had a soporific effect, we controlled the various magnitudes of phase delay produced by the other study interventions. Melatonin (n=18) and placebo (n=18) groups were formed by matching a melatonin participant with a placebo participant that had a similar baseline and final DLMO (±1 h). Sleep log measurements of total sleep time (TST) and actigraphic measurements of sleep latency, TST, and three movement indices for the two groups were examined. Although melatonin was associated with small improvements in sleep quality and quantity, the differences were not statistically significant by analysis of variance. However, binomial analysis indicated that melatonin participants were more likely to sleep better than their placebo counterparts on some days with some measures. It was concluded that, the soporific effect of melatonin is small when administered prior to 7 h daytime sleep periods following night shift work.     

Bright-light exposure during daytime sleeping affects nocturnal melatonin secretion after simulated night work

The guidelines for night and shift workers recommend that after night work, they should sleep in a dark environment during the daytime. However, staying in a dark environment during the daytime reduces nocturnal melatonin secretion and delays its onset. Daytime bright-light exposure after night work is important for melatonin synthesis the subsequent night and for maintaining the circadian rhythms. However, it is not clear whether daytime sleeping after night work should be in a dim- or a bright-light environment for maintaining melatonin secretion. The aim of this study, therefore, was to evaluate the effect of bright-light exposure during daytime sleeping on nocturnal melatonin secretion after simulated night work. Twelve healthy male subjects, aged 24.8 ± 4.6 (mean ± SD), participated in 3-day sessions under two experimental conditions, bright light or dim light, in a random order. On the first day, the subjects entered the experimental room at 16:00 and saliva samples were collected every hour between 18:00 and 00:00 under dim-light conditions. Between 00:00 and 08:00, they participated in tasks that simulated night work. At 10:00 the next morning, they slept for 6 hours under either a bright-light condition (>3000 lx) or a dim-light condition (<50 lx). In the evening, saliva samples were collected as on the first day. The saliva samples were analyzed for melatonin concentration. Activity and sleep times were recorded by a wrist device worn throughout the experiment. In the statistical analysis, the time courses of melatonin concentration were compared between the two conditions by three-way repeated measurements ANOVA (light condition, day and time of day). The change in dim light melatonin onset (ΔDLMO) between the first and second days, and daytime and nocturnal sleep parameters after the simulated night work were compared between the light conditions using paired t-tests. The ANOVA results indicated a significant interaction (light condition and3 day) (p = .006). Post hoc tests indicated that in the dim-light condition, the melatonin concentration was significantly lower on the second day than on the first day (p = .046); however, in the bright-light condition, there was no significant difference in the melatonin concentration between the days (p = .560). There was a significant difference in ΔDLMO between the conditions (p = .015): DLMO after sleeping was advanced by 11.1 ± 17.4 min under bright-light conditions but delayed for 7.2 ± 13.6 min after sleeping under dim-light conditions. No significant differences were found in any sleep parameter. Our study demonstrated that daytime sleeping under bright-light conditions after night work could not reduce late evening melatonin secretion until midnight or delay the phase of melatonin secretion without decreasing the quality of the daytime sleeping. Thus, these results suggested that, to enhance melatonin secretion and to maintain their conventional sleep–wake cycle, after night work, shift workers should sleep during the daytime under bright-light conditions rather than dim-light conditions.     

Calculating the dim light melatonin onset: the impact of threshold and sampling rate

The dim light melatonin onset (DLMO) is the most reliable circadian phase marker in humans, but the cost of assaying samples is relatively high. Therefore, the authors examined differences between DLMOs calculated from hourly versus half-hourly sampling and differences between DLMOs calculated with two recommended thresholds (a fixed threshold of 3 pg/mL and a variable "3k" threshold equal to the mean plus two standard deviations of the first three low daytime points). The authors calculated these DLMOs from salivary dim light melatonin profiles collected from 122 individuals (64 women) at baseline. DLMOs derived from hourly sampling occurred on average only 6-8?min earlier than the DLMOs derived from half-hourly saliva sampling, and they were highly correlated with each other (r?≥?0.89, p?30?min from the DLMO derived from half-hourly sampling. The 3 pg/mL threshold produced significantly less variable DLMOs than the 3k threshold. However, the 3k threshold was significantly lower than the 3 pg/mL threshold (p?相似文献   

A randomized controlled trial with bright light and melatonin for delayed sleep phase disorder: Effects on subjective and objective sleep

Delayed sleep phase disorder (DSPD) is assumed to be common amongst adolescents, with potentially severe consequences in terms of school attendance and daytime functioning. The most common treatment approaches for DSPD are based on the administration of bright light and/or exogenous melatonin with or without adjunct behavioural instructions. Much is generally known about the chronobiological effects of light and melatonin. However, placebo-controlled treatment studies for DSPD are scarce, in particular in adolescents and young adults, and no standardized guidelines exist regarding treatment. The aim of the present study was, therefore, to investigate the short- and long-term effects on sleep of a DSPD treatment protocol involving administration of timed bright light and melatonin alongside gradual advancement of rise time in adolescents and young adults with DSPD in a randomized controlled trial and an open label follow-up study. A total of 40 adolescents and young adults (age range 16–25 years) diagnosed with DSPD were recruited to participate in the study. The participants were randomized to receive treatment for two weeks in one of four treatment conditions: dim light and placebo capsules, bright light and placebo capsules, dim light and melatonin capsules or bright light and melatonin capsules. In a follow-up study, participants were re-randomized to either receive treatment with the combination of bright light and melatonin or no treatment in an open label trial for approximately three months. Light and capsules were administered alongside gradual advancement of rise times. The main end points were sleep as assessed by sleep diaries and actigraphy recordings and circadian phase as assessed by salivary dim light melatonin onset (DLMO). During the two-week intervention, the timing of sleep and DLMO was advanced in all treatment conditions as seen by about 1?h advance of bed time, 2?h advance of rise time and 2?h advance of DLMO in all four groups. Sleep duration was reduced with approximately 1?h. At three-month follow-up, only the treatment group had maintained an advanced sleep phase. Sleep duration had returned to baseline levels in both groups. In conclusion, gradual advancement of rise time produced a phase advance during the two-week intervention, irrespective of treatment condition. Termination of treatment caused relapse into delayed sleep times, whereas long-term treatment with bright light and melatonin (three months) allowed maintenance of the advanced sleep phase.     

Reduced Phase-Advance of Plasma Melatonin After Bright Morning Light in The Luteal,But Not Follicular,Menstrual Cycle Phase in Premenstrual Dysphoric Disorder: An Extended Study

The authors previously observed blunted phase-shift responses to morning bright light in women with premenstrual dysphoric disorder (PMDD). The aim of this study was to determine if these findings could be replicated using a higher-intensity, shorter-duration light pulse and to compare these results with the effects of an evening bright-light pulse. In 17 PMDD patients and 14 normal control (NC) subjects, the authors measured plasma melatonin at 30-min intervals from 18:00 to 10:00?h in dim (<30 lux) or dark conditions the night before (Night 1) and after (Night 3) a bright-light pulse (administered on Night 2) in both follicular and luteal menstrual cycle phases. The bright light (either 3000 lux for 6?h or 6000 lux for 3?h) was given either in the morning (AM light), 7?h after the dim light melatonin onset (DLMO) measured the previous month, or in the evening (PM light), 3?h after the DLMO. In the luteal, but not in the follicular, phase, AM light advanced melatonin offset between Night 1 and Night 3 significantly less in PMDD than in NC subjects. The effects of PM light were not significant, nor were there significant effects of the light pulse on melatonin measures of onset, duration, peak, or area under the curve. These findings replicated the authors’ previous finding of a blunted phase-shift response to morning bright light in the luteal, but not the follicular, menstrual cycle phase in PMDD compared with NC women, using a brighter (6000 vs. 3000 lux) light pulse for a shorter duration (3 vs. 6?h). As the effect of PM bright light on melatonin phase-shift responses did not differ between groups or significantly alter other melatonin measures, these results suggest that in PMDD there is a luteal-phase subsensitivity or an increased resistance to morning bright-light cues that are critical in synchronizing human biological rhythms. The resulting circadian rhythm malsynchonization may contribute to the occurrence of luteal phase depressive symptoms in women with PMDD. (Author correspondence: bparry@ucsd.edu)     

Effects of different light intensities in the morning on dim light melatonin onset

The present study evaluated the effects of exposure to light intensity in the morning on dim light melatonin onset (DLMO). The tested light intensities were 750 lux, 150 lux, 3000 lux, 6000 lux and 12,000 lux (horizontal illuminance at cornea), using commercial 5000 K fluorescent lamps. Eleven healthy males aged 21-31 participated in 2-day experiments for each light condition. On the first experimental day (day 1), subjects were exposed to dim light (<30 lux) for 3 h in the morning (09:00-12:00). On the same day, saliva samples were taken in dim light (<30 lux) every 30 min from 21:00 to 01:00 to determine the DLMO phase. The subjects were allowed to sleep from 01:00 to 08:00. On the second experimental day (day 2), the subjects were exposed to experimental light conditions for 3 h in the morning. The experimental schedule after light exposure was the same as on day 1. On comparing day 2 with day 1, significant phase advances of DLMO were obtained at 3000 lux, 6000 lux and 12,000 lux. These findings indicate that exposure to a necessary intensity from an ordinary light source, such as a fluorescent lamp, in the morning within one day affects melatonin secretion.     

Circadian Uses of Melatonin in Humans

Melatonin in humans can be an independent or dependent variable. Measurement of endogenous melatonin levels under dim‐light conditions, particularly the dim‐light melatonin onset (DLMO), has received increasing attention among researchers, and for clinicians it may soon become a convenient test that can be done at home using saliva collections in the evening, without interfering with sleep. Melatonin, even at low physiological doses, can cause advances (shifts to an earlier time) or delays (shifts to a later time) depending on when it is administered on its phase‐response curve (in most sighted people, these times are approximately in the p.m. and in the a.m., respectively). Although both bright light and melatonin can be used separately or together in the treatment of circadian phase disorders in sighted people—such as advanced and delayed sleep phase syndromes, jet lag, shift‐work maladaptation, and winter depression (seasonal affective disorder, or SAD)—melatonin is the treatment of choice in totally blind people. These people provide a unique opportunity to study the human circadian system without the overwhelming effects of ocularly mediated light, thus permitting us to establish that all blind free‐runners (BFRs) studied under high resolution appear to have phase‐advancing and phase‐delaying responses to as yet unidentified zeitgebers (time givers) that are usually too weak to result in entrainment.     

Dim light melatonin onset in alcohol-dependent men and women compared with healthy controls

Sleep disturbances in alcohol-dependent (AD) individuals may persist despite abstinence from alcohol and can influence the course of the disorder. Although the mechanisms of sleep disturbances of AD are not well understood and some evidence suggests dysregulation of circadian rhythms, dim light melatonin onset (DLMO) has not previously been assessed in AD versus healthy control (HC) individuals in a sample that varied by sex and race. The authors assessed 52 AD participants (mean?±?SD age: 36.0?±?11.0 yrs of age, 10 women) who were 3-12 wks since their last drink (abstinence: 57.9?±?19.3 d) and 19 age- and sex-matched HCs (34.4?±?10.6 yrs, 5 women). Following a 23:00-06:00?h at-home sleep schedule for at least 5 d and screening/baseline nights in the sleep laboratory, participants underwent a 3-h extension of wakefulness (02:00?h bedtime) during which salivary melatonin samples were collected every 30?min beginning at 19:30?h. The time of DLMO was the primary measure of circadian physiology and was assessed with two commonly used methodologies. There was a slower rate of rise and lower maximal amplitude of the melatonin rhythm in the AD group. DLMO varied by the method used to derive it. Using 3 pg/mL as threshold, no significant differences were found between the AD and HC groups. Using 2 standard deviations above the mean of the first three samples, the DLMO in AD occurred significantly later, 21:02?±?00:41?h, than in HC, 20:44?±?00:21?h (t?=?-2.4, p?=?.02). Although melatonin in the AD group appears to have a slower rate of rise, using well-established criteria to assess the salivary DLMO did not reveal differences between AD and HC participants. Only when capturing melatonin when it is already rising was DLMO found to be significantly delayed by a mean 18?min in AD participants. Future circadian analyses on alcoholics should account for these methodological caveats.     

EVENING DAYLIGHT MAY CAUSE ADOLESCENTS TO SLEEP LESS IN SPRING THAN IN WINTER

Sleep restriction commonly experienced by adolescents can stem from a slower increase in sleep pressure by the homeostatic processes and from phase delays of the circadian system. With regard to the latter potential cause, the authors hypothesized that because there is more natural evening light during the spring than winter, a sample of adolescent students would be more phase delayed in spring than in winter, would have later sleep onset times, and because of fixed school schedules would have shorter sleep durations. Sixteen eighth-grade subjects were recruited for the study. The authors collected sleep logs and saliva samples to determine their dim light melatonin onset (DLMO), a well-established circadian marker. Actual circadian light exposures experienced by a subset of 12 subjects over the course of 7 days in winter and in spring using a personal, head-worn, circadian light measurement device are also reported here. Results showed that this sample of adolescents was exposed to significantly more circadian light in spring than in winter, especially during the evening hours when light exposure would likely delay circadian phase. Consistent with the light data, DLMO and sleep onset times were significantly more delayed, and sleep durations were significantly shorter in spring than in winter. The present ecological study of light, circadian phase, and self-reported sleep suggests that greater access to evening daylight in the spring may lead to sleep restriction in adolescents while attending school. Therefore, lighting schemes that reduce evening light in the spring may encourage longer sleep times in adolescents. (Author correspondence: figuem@rpi.edu)