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   

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?<?.001). However, in up to 19% of cases the DLMO derived from hourly sampling was >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?<?.001). The DLMOs calculated with the 3k method were significantly earlier (by 22–24?min) than the DLMOs calculated with the 3 pg/mL threshold, regardless of sampling rate. These results suggest that in large research studies and clinical settings, the more affordable and practical option of hourly sampling is adequate for a reasonable estimate of circadian phase. Although the 3 pg/mL fixed threshold is less variable than the 3k threshold, it produces estimates of the DLMO that are further from the initial rise of melatonin. (Author correspondence: Helen_J_Burgess@rush.edu)     

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.     

The dim light melatonin onset, melatonin assays and biological rhythm research in humans

The most useful marker for human circadian phase position is the dim light melatonin onset (DLMO). This is optimally obtained by sampling blood or saliva in the evening at intervals of 30 min or less. Ambient light intensity should not exceed 30-50 lx. For many years, the DLMO was determined mainly with the 'gold standard' GCMS technique for measuring melatonin in human plasma. However, new and improved RIAs now provide the requisite sensitivity and accuracy (specificity) for detecting the time that low daytime levels begin to increase in the evening: the lower the operational threshold for the DLMO, the more reliable it is as a phase marker.     

Can the circadian phase be estimated from self-reported sleep timing in patients with Delayed Sleep Wake Phase Disorder to guide timing of chronobiologic treatment?

Introduction: The efficacy of bright light and/or melatonin treatment for Delayed Sleep Wake Phase Disorder (DSWPD) is contingent upon an accurate clinical assessment of the circadian phase. However, the process of determining this circadian phase can be costly and is not yet readily available in the clinical setting. The present study investigated whether more cost-effective and convenient estimates of the circadian phase, such as self-reported sleep timing, can be used to predict the circadian phase and guide the timing of light and/or melatonin treatment (i.e. dim-light melatonin onset, core body temperature minimum and melatonin secretion mid-point) in a sample of individuals with DSWPD. Method: Twenty-four individuals (male = 17; mean age = 21.96, SD = 5.11) with DSWPD were selected on the basis of ICSD-3 criteria from a community-based sample. The first 24-hours of a longer 80-hour constant laboratory ultradian routine were used to determine core body temperature minimum (cBT^min), dim-light melatonin onset (DLMO) and the midpoint of the melatonin secretion period (DLM^mid = [DLM°^ff–DLMO]/2). Prior to the laboratory session subjective sleep timing was assessed using a 7-day sleep/wake diary, the Pittsburgh Sleep Quality Index (PSQI), and the Delayed Sleep Phase Disorder Sleep Timing Questionnaire (DSPD-STQ). Results: Significant moderate to strong positive correlations were observed between self-reported sleep timing variables and DLMO, cBT^min and DLM^mid. Regression equations revealed that the circadian phase (DLMO, cBT^min and DLM^mid) was estimated within ±1.5 hours of the measured circadian phase most accurately by the combination of sleep timing measures (88% of the sample) followed by sleep diary reported midsleep (83% of the sample) and sleep onset time (79% of the sample). Discussion: These findings suggest that self-reported sleep timing may be useful clinically to predict a therapeutically relevant circadian phase in DSWPD.     

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.     

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.     

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.     

Circadian phase-shifting effects of nocturnal exercise in older compared with young adults

Exercise can phase shift the circadian rhythms of young adults if performed at the right time of day. Similar research has not been done in older adults. This study examined the circadian phase-delaying effects of a single 3-h bout of low-intensity nocturnal exercise in older (n = 8; 55-73 yr old) vs. young (n = 8; 20-32 yr old) adults. The exercise occurred at the beginning of each subject's habitual sleep time, and subjects sat in a chair in dim light during the corresponding time in the control condition. The dim-light melatonin onset (DLMO) was used as the circadian phase marker. The DLMO phase delayed more after the exercise than after the control condition. On average, the difference in phase shift between the exercise and control conditions was similar for older and young subjects, demonstrating that the phase-shifting effects of exercise on the circadian system are preserved in older adults. Therefore, exercise may potentially be a useful treatment to help adjust circadian rhythms in older and young adults.     

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)     

Phase relationships between sleep-wake cycle and underlying circadian rhythms in Morningness-Eveningness

A shorter phase angle between habitual wake time and underlying circadian rhythms has been reported in evening types (E types) compared to morning-types (M types). In this study, phase angles were compared between 12 E types and 12 M types to verify if this difference was observed when the sleep schedule was relatively free from external social constraints. Subjects were selected according to their Morningness-Eveningness Questionnaire score (MEQ score). There were 6 men and 6 women in each group (ages 19-34 years), and all had a habitual sleep duration between 7 and 9 h. Sleep schedule was recorded by actigraphy and averaged over 7 days. Circadian phase was estimated by the hour of temperature minimum (T(min)) in a 26-h recording and by the timing of the onset of melatonin secretion (dim-light melatonin onset [DLMO]) measured in saliva samples. Phase angles were defined as the interval between phase markers and averaged wake time. Results showed that, in the present experimental conditions, phase angles were very similar in the 2 groups of subjects. However, results confirmed the previously reported correlation between phase and phase angle, showing that a later circadian phase was associated with a shorter phase angle. Gender comparisons showed that for a same MEQ score, women had an earlier DLMO and a longer phase angle between DLMO and wake time. Despite a significant difference in the averaged circadian phases between E-type and M-type groups, there was an overlap in the circadian phases of the subjects of the 2 groups. Further comparisons were made between the 2 circadian types, separately for the subgroups with overlapping or nonoverlapping circadian phases. In both subgroups, the significant difference between MEQ scores, bedtimes, and wake times were maintained in the expected direction. In the subgroup with nonoverlapping circadian phases, phase angles were shorter in E-type subjects, in accordance with previous studies. However, in the overlapping subgroup, phase angles were significantly longer in E types compared to M types. Results suggest that the morningness-eveningness preference identified by the MEQ score refers to 2 distinct mechanisms, 1 associated with a difference in circadian period and phase of entrainment and the other associated with chronobiological aspects of sleep regulation.     

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.     

The Dim Light Melatonin Onset as a Marker for Orcadian Phase Position

Masking is known to affect a variety of circadian rhythms, making it difficult to use them as reliable markers of circadian phase position. Melatonin may be unique in that it appears to be masked only by (bright) light. Sleep and activity do not appear to influence the melatonin rhythm. By measuring the onset of melatonin production, a clearly demarcated event, we can reliably assess circadian phase position, provided blood is sampled under dim light (the dim light melatonin onset, or DL.MO). The DLMO has been useful in assessing the phase-shifting properties of bright light and in phase typing patients with chronobiologic disorders, such as winter depression.     

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.     

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.     

Alteration of internal circadian phase relationships after morning versus evening carbohydrate-rich meals in humans

The effects of a single morning and evening carbohydrate-rich meal for 3 consecutive days on circadian phase of core body temperature (CBT), heart rate, and salivary melatonin rhythms were compared under controlled constant routine conditions. In 10 healthy young men entrained to a natural light-dark cycle with regular sleep timing, CBT and heart rate were significantly elevated for approximately 8 h after the last evening carbohydrate-rich meal (EM), and nocturnal melatonin secretion (as measured by salivary melatonin and urinary 6-sulphatoxymelatonin levels) was reduced, compared to the morning carbohydrate-rich meal (MM) condition. Thus, circadian phase could not be measured until the following day due to this acute masking effect. The day after the last meal intervention, MM showed a significant advanced circadian phase position in CBT (+59+/-12 min) and heart rate (+43+/-18 min) compared to EM. However, dim-light melatonin onset was not significantly changed (+15+/-13 min). The results are discussed with respect to central (light-entrainable) and peripheral (food-entrainable) oscillators. Food may be a zeitgeber in humans for the food-entrainable peripheral oscillators, but melatonin data do not support such a conclusion for the light-entrainable oscillator in the suprachiasmatic nucleus.     

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. (Author correspondence: daconroy@med.umich.edu)     

Partial sleep deprivation reduces phase advances to light in humans

Partial sleep deprivation is increasingly common in modern society. This study examined for the first time if partial sleep deprivation alters circadian phase shifts to bright light in humans. Thirteen young healthy subjects participated in a repeated-measures counterbalanced design with 2 conditions. Each condition had baseline sleep, a dim-light circadian phase assessment, a 3-day phase-advancing protocol with morning bright light, then another phase assessment. In one condition (no sleep deprivation), subjects had an 8-h sleep opportunity per night during the advancing protocol. In the other condition (partial sleep deprivation), subjects were kept awake for 4 h in near darkness (<0.25 lux), immediately followed by a 4-h sleep opportunity per night during the advancing protocol. The morning bright light stimulus was four 30-min pulses of bright light (~5000 lux), separated by 30-min intervals of room light. The light always began at the same circadian phase, 8 h after the baseline dim-light melatonin onset (DLMO). The average phase advance without sleep deprivation was 1.8 ± 0.6 (SD) h, which reduced to 1.4 ± 0.6 h with partial sleep deprivation (p < 0.05). Ten of the 13 subjects showed reductions in phase advances with partial sleep deprivation, ranging from 0.2 to 1.2 h. These results indicate that short-term partial sleep deprivation can moderately reduce circadian phase shifts to bright light in humans. This may have significant implications for the sleep-deprived general population and for the bright light treatment of circadian rhythm sleep disorders such as delayed sleep phase disorder.