Salivary Dim Light Melatonin Onset Research Articles

Estimating Dim Light Melatonin Onset (DLMO) Phase in Adolescents Using Summer or School-Year Sleep/Wake Schedules

This analysis examined associations between the salivary dim light melatonin onset (DLMO) phase and self-selected sleep/ wake schedules in groups of children and adolescents during summer vacation and during the school year to determine the degree to which sleep/wake patterns can estimate salivary DLMO phase. Participants slept at home on self-selected schedules for 5 consecutive nights and reported their bedtime and wake-up time via daily telephone messages. Salivary melatonin was sampled in the laboratory on one evening every 30 minutes in dim light (< 50 lux) to determine DLMO phase. Within group bivariate regressions between sleep pattern measures (bedtime, wake-up time, and midsleep time) and DLMO phase were computed. One group, ages 9 to 17 years (mean age = 12.5, SD = 2.3 years, 74 males, 75 females) contributed 149 DLMO phase and sleep/wake pattern measures while on a school year schedule ("school group"). A separate group, ages 9 to 16 years (mean age = 13.1, SD = 1.3 years, 30 males, 29 females) contributed 59 DLMO phase and sleep/wake pattern measures while on a summer schedule ("summer group"). Bedtime, midsleep time, and wake-up time were positively correlated with DLMO phase in both groups. Although all correlation coefficients for the summer group were statistically greater compared to the school group, the regression equations predicted DLMO phase within +/- 1 hour of the measured DLMO phase in approximately 80% for both groups. DLMO phase can be estimated using self-selected sleep/wake patterns during the school year or summer vacation in healthy children and adolescents.

Circadian Phase in Delayed Sleep Phase Syndrome: Predictors and Temporal Stability Across Multiple Assessments

To assess temporal stability across multiple assessments and predictors of circadian phase in participants with delayed sleep phase syndrome (DSPS), relative to normal-sleeping matched controls. Circadian phase was assessed by salivary dim light melatonin onset (DLMO) during 3 laboratory visits, separated by at least 5 days--2 scheduled at the end of the week (Friday) and 1 scheduled at the end of the weekend (Sunday). Eight young volunteers who met International Classification of Sleep Disorders-Revised criteria for DSPS, and 8 age- and sex-matched controls (age range 19-27 years old). N/A. As expected, salivary DLMO occurred significantly later in patients with DSPS than in controls (F 10.561, p = .006). However, circadian phase did not change significantly across the 3 DLMO assessments in either group. Estimations of circadian phase were not significantly different in the assessments conducted on weekdays versus weekends. Predictors of circadian phase included time of morning light exposure (R2 = 0.777; p < .001), recent wake time (R2 = 0.701, p < .001), and self-reported chronotype (R2 = 0.320, p = .016). DLMO preceded wake time in both groups by approximately 10.75 hours. Across serial laboratory assessments on an ad lib sleep schedule, patients with DSPS appeared more similar to than different from normal-sleeping control subjects, except for a stable delay in circadian phase.

No evidence to support an association of PER3 clock gene polymorphism with ADHD-related idiopathic chronic sleep onset insomnia

Idiopathic chronic sleep onset insomnia (SOI) in children with Attention‐Deficit/Hyperactivity Disorder (ADHD) shows typical characteristics of the delayed sleep phase syndrome and could, therefore, be considered a circadian rhythm sleep disorder. A variable number tandem repeat (VNTR) polymorphism of the clock gene PER3 is associated with the delayed sleep phase syndrome and, hence, may associate with ADHD-related chronic SOI as well. Here, we investigated an association between ADHD-related chronic SOI and the VNTR polymorphism of PER3 in 10 medication naïve children with rigorously diagnosed ADHD and SOI (ADHD-SOI), and in 10 normal controls. Actigraphic sleep onset and sleep duration and salivary dim light melatonin onset (DLMO) were evaluated in ADHD-SOI. The 4-repeat allele frequency was lower in ADHD-SOI (0.65) than in normal controls (0.75) (p = 0.73) with an odds ratio of 0.62 (CI 0.16 – 2.4). In ADHD-SOI, mean (±SD) DLMO (21:38 ± 0:50 h), sleep onset (22:17 ± 0:46 h), and sleep duration (9:26 ± 0:41 h) were not significantly related to the 4-repeat allele frequency. The present findings suggest no association between ADHD-related idiopathic chronic sleep onset insomnia and the PER3 VNTR polymorphism.

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.

Daily rhythm of cerebral blood flow velocity

BackgroundCBFV (cerebral blood flow velocity) is lower in the morning than in the afternoon and evening. Two hypotheses have been proposed to explain the time of day changes in CBFV: 1) CBFV changes are due to sleep-associated processes or 2) time of day changes in CBFV are due to an endogenous circadian rhythm independent of sleep. The aim of this study was to examine CBFV over 30 hours of sustained wakefulness to determine whether CBFV exhibits fluctuations associated with time of day.MethodsEleven subjects underwent a modified constant routine protocol. CBFV from the middle cerebral artery was monitored by chronic recording of Transcranial Doppler (TCD) ultrasonography. Other variables included core body temperature (CBT), end-tidal carbon dioxide (EtCO2), blood pressure, and heart rate. Salivary dim light melatonin onset (DLMO) served as a measure of endogenous circadian phase position.ResultsA non-linear multiple regression, cosine fit analysis revealed that both the CBT and CBFV rhythm fit a 24 hour rhythm (R2 = 0.62 and R2 = 0.68, respectively). Circadian phase position of CBT occurred at 6:05 am while CBFV occurred at 12:02 pm, revealing a six hour, or 90 degree difference between these two rhythms (t = 4.9, df = 10, p < 0.01). Once aligned, the rhythm of CBFV closely tracked the rhythm of CBT as demonstrated by the substantial correlation between these two measures (r = 0.77, p < 0.01).ConclusionIn conclusion, time of day variations in CBFV have an approximately 24 hour rhythm under constant conditions, suggesting regulation by a circadian oscillator. The 90 degree-phase angle difference between the CBT and CBFV rhythms may help explain previous findings of lower CBFV values in the morning. The phase difference occurs at a time period during which cognitive performance decrements have been observed and when both cardiovascular and cerebrovascular events occur more frequently. The mechanisms underlying this phase angle difference require further exploration.

Idiopathic Chronic Sleep Onset Insomnia in Attention‐Deficit/Hyperactivity Disorder: A Circadian Rhythm Sleep Disorder

To investigate whether ADHD‐related sleep‐onset insomnia (SOI) is a circadian rhythm disorder, we compared actigraphic sleep estimates, the circadian rest‐activity rhythm, and dim light melatonin onset (DLMO) in ADHD children having chronic idiopathic SOI with that in ADHD children without sleep problems. Participants were 87 psychotropic-medication-naïve children, aged 6 to 12 yrs, with rigorously diagnosed ADHD and SOI (ADHD‐SOI) and 33 children with ADHD without SOI (ADHD‐noSOI) referred from community mental health institutions and pediatric departments of non‐academic hospitals in The Netherlands. Measurements were 1 wk, 24 h actigraphy recordings and salivary DLMO. The mean (±SD) sleep onset time was 21:38±0:54 h in ADHD‐SOI, which was significantly (p<0.001) later than that of 20:49±0:49 h in ADHD‐noSOI. DLMO was significantly later in ADHD‐SOI (20:32±0:55 h), compared with ADHD‐noSOI (19:47±0:49 h; p<0.001). Wake‐up time in ADHD‐SOI was later than in ADHD‐noSOI (p=0.002). There were no significant between‐group differences in sleep maintenance, as estimated by number of wake bouts and activity level in the least active 5 h period, or inter‐ and intradaily rhythm variability. We conclude that children with ADHD and chronic idiopathic sleep‐onset insomnia show a delayed sleep phase and delayed DLMO, compared with ADHD children without SOI.

Extraocular light therapy in winter depression: a double-blind placebo-controlled study

Background: It has been hypothesized that the circadian pacemaker is phase delayed in seasonal affective disorder, (SAD) winter type, and that the phase advance resulting from morning ocular light accounts for the efficacy of light therapy. Extraocular light has been reported to produce phase-shifts of the human circadian pacemaker. This allows a double-blind, placebo-controlled study of light therapy in SAD. Methods: Twenty-nine SAD patients participated. Clinical state was measured on days 1, 8, and 15 of the protocol. From days 4 through 8, 15 patients (4 M, 11 F) received extraocular light by fiberoptic illumination, and 14 (4 M, 10 F) placebo (no light) in the popliteal fossae, from 8 am to 11 am. In the evenings of days 3 and 8, the salivary dim light melatonin onset (DLMO) was assessed. Patients completed daily self-ratings on mood, alertness, and sleep. Results: Both conditions showed a progressive improvement of clinical state over time. Between conditions, no significant differences were observed in clinical scores, the self-ratings on mood and alertness, and in timing of the DLMO before and directly after treatment. Conclusions: The response to extraocular light therapy in SAD patients did not exceed its placebo effect. Extraocular light did not induce a phase shift of the circadian pacemaker.

A single dose of melatonin prevents the phase delay associated with a delayed weekend sleep pattern.

This study was designed to test the hypotheses that a delayed weekend sleep pattern may lead to a phase delay of the endogenous circadian rhythm, and that melatonin administration can counteract the phase delay and prevent the sleep and functional impairments associated with this sleep pattern. A within-subject, counterbalanced design was used in which each subject participated in both placebo and melatonin conditions. Subjects' sleep-wake schedules were delayed by two hours on Friday and Saturday to simulate the delayed weekend sleep pattern. Six mg of melatonin or a placebo pill was administered double blind on Sunday late afternoon. N/A. Ten healthy volunteers (mean age = 22.1 years old). Salivary dim-light melatonin onset (DLMO) was measured on Friday and Monday nights. Subject's sleep was recorded with polysomnography on Sunday night and their levels of sleepiness, cognitive functioning and mood were assessed on Sunday night and Monday morning. Results show that the delayed weekend sleep pattern caused a 31.6 min delay of the endogenous melatonin rhythm. Melatonin administration counteracted the phase delay of endogenous melatonin onset. On Sunday, melatonin administration increased the sleepiness throughout the evening and reduced sleep onset latency at bedtime. On Monday morning, subjective sleepiness was decreased in the melatonin condition. A delayed weekend sleep pattern did show a mild phase-delay effect on the endogenous circadian rhythm. A single dose of melatonin can acutely reverse the weekend drift.

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.

FAILURE OF EXTRAOCULAR LIGHT TO FACILITATE CIRCADIAN RHYTHM REENTRAINMENT IN HUMANS

Although extraocular light can entrain the circadian rhythms of invertebrates and nonmammalian vertebrates, almost all studies show that the mammalian circadian system can only be affected by light to the eyes. The exception is a recent study by Campbell and Murphy that reported phase shifts in humans to bright light applied with fiber-optic pads behind the knees (popliteal region). We tested whether this extraocular light stimulus could accelerate the entrainment of circadian rhythms to a shift of the sleep schedule, as occurs in shift work or jet lag. In experiment 1, the sleep/dark episodes were delayed 8h from baseline for 2 days, and 3h light exposures were timed to occur before the temperature minimum to help delay circadian rhythms. There were three groups: (1) bright (about 13,000 lux) extraocular light from fiber-optic pads, (2) control (dim light, 10–20 lux), and (3) medium-intensity (about 1000 lux) ocular light from light boxes. In experiment 2, the sleep/dark episodes were inverted, and extraocular light was applied either before the temperature minimum to help delay circadian rhythms or after the temperature minimum to help advance rhythms. Circadian phase markers were the salivary dim light melatonin onset (DLMO) and the rectal temperature minimum. There was no evidence that the popliteal extraocular light had a phase-shifting effect in either experiment. Possible reasons for phase shifts in the Campbell and Murphy study and not the current study include the many differences between the protocols. In the current study, there was substantial sleep deprivation before the extraocular light was applied. There was a large shift in the sleep/dark schedule, rather than allowing subjects to sleep each day from midnight to noon, as in the Campbell and Murphy study. Also, when extraocular light was applied in the current protocol, subjects did not experience a change from sleeping to awake, a change in posture (from lying in bed to sitting in a chair), or a change in ocular light (from dark to dim light). Further research is necessary to determine the conditions under which extraocular light might produce phase shifts in human circadian rhythms. (Chronobiology International, 17(6), 807–826, 2000).

Adolescent sleep patterns, circadian timing, and sleepiness at a transition to early school days.

This study examined effects on adolescent sleep patterns, sleepiness, and circadian phase of a school transition requiring an earlier start. Adolescents were evaluated in 9th and 10th grades; school start time in 9th grade was 0825 and in 10th grade was 0720. Assessments at each point included 2 weeks of actigraphy and sleep diaries at home, followed by a 22-hour laboratory evaluation, including evening saliva samples every 30 minutes in dim light for determination of dim-light salivary melatonin onset phase (DLSMO), overnight sleep monitoring, and multiple sleep latency test (MSLT). Twenty-five females and 15 males, ages 14 to 16.2 were enrolled; 32 completed the study in 9th grade and 26 completed in 10th grade. Participants kept their own schedules, except that laboratory nights were scheduled based upon school-night sleep patterns. According to actigraphy, students woke earlier on school days in 10th than in 9th grade, but they did not go to sleep earlier and they slept less. DLSMO phase was later in 10th grade (mean = 2102) than 9th grade (mean = 2024). Sleep latency on MSLT overall was shorter in 10th (mean = 8.5 minutes) than in 9th (mean = 11.4 minutes), particularly on the first test of the morning at 0830 (5.1 vs 10.9 minutes). Two REM episodes on MSLT occurred in 16% of participants in 10th grade; one REM episode occurred in 48%. When those with REM sleep on one or both morning MSLTs (n = 11) were compared to those without morning REM, significant differences included shorter sleep latency on the first test, less slow wave sleep the night before, and later DLSMO phase in those who had morning REM. Early start time was associated with significant sleep deprivation and daytime sleepiness. The occurrence of REM sleep on MSLT indicates that clinicians should exercise caution in interpreting MSLT REM sleep in adolescents evaluated on their "usual" schedules. Psychosocial influences and changes in bioregulatory systems controlling sleep may limit teenagers' capacities to make adequate adjustments to an early school schedule.

An Approach to Studying Circadian Rhythms of Adolescent Humans

The "long nights" protocol was designed to evaluate sleep processes and circadian rhythm parameters in young humans. A total of 19 children (10 boys, ages 11.2 to 14.1 years [mean = 12.7 +/- 1.0], and 9 girls, ages 12.2 to 14.4 years [mean = 13.1 +/- 0.7]) took part in the study. Sleep/wake initially was assessed at home using actigraphy and diary for 1 week on each child's self-selected schedule followed by an 8-night fixed light-dark (LD) condition, while sleeping from 22:00 to 08:00 h and wearing an eye mask to exclude as much light as possible. Phase measurements included 4-night mean actigraphically estimated sleep onset and offset as well as 1-night dim light salivary melatonin onset (DLSMO) phase at the end of each condition. Subjects then lived in the laboratory for 6 consecutive cycles: Day 1 LD = 14:10 h, lights out 22:00 to 08:00 h; Days 2-4 LD = 6:18 h, lights out 18:00 to 12:00 h; Days 5-6 = constant routine in continuous dim light (about 20 lux); Night 6 = 14 h recovery sleep. Phase markers (sleep onset, sleep offset, DLSMO) were significantly less dispersed after the fixed LD as compared to the self-selected condition, indicating efficacy of the LD protocol. Phase markers were correlated at the self-selected assessment (sleep onset vs. sleep offset r = .72; DLSMO vs. sleep onset r = .82; DLSMO vs. sleep offset r = .76) but not on the fixed schedule, probably due to restricted range. The constant routine provided additional phase markers, melatonin offset and midphase. Offset phase of melatonin secretion was significantly correlated with age (r = .62) and Tanner stage (r = .62). In conclusion, these preliminary data indicate a relationship between adolescent development and circadian phase. Thus, the long nights protocol is a feasible way in which to assess circadian parameters in young humans as well as to examine intrinsic sleep processes.