Contemporaneous melatonin administration modifies the circadian response to nocturnal bright light stimuli

1997 ◽  
Vol 272 (2) ◽  
pp. R482-R486 ◽  
Author(s):  
A. Cagnacci ◽  
R. Soldani ◽  
S. S. Yen
Keyword(s):  
Light Exposure ◽  
Light Stimulus ◽  
Core Body Temperature ◽  
Bright Light ◽  
Phase Shifts ◽  
Double Blind ◽  
Circadian Phase ◽  
Melatonin Administration ◽  
Baseline Evaluation ◽  
Light Stimuli

We investigated whether the contemporaneous administration of melatonin can modify circadian phase shifts induced by bright light stimuli. After a baseline evaluation, 10 women were exposed for three consecutive nights to a 4-h bright light stimulus (>3,000 lx) initiated at the time of the estimated core body temperature (BT(c)) nadir. Along with light, each woman orally received, randomly and in a double-blind fashion, placebo (n = 5) or melatonin (n = 5; 1 mg 30 min before and 0.75 mg 120 min after the start of light exposure). Daily rhythms were reevaluated at the end of treatment. Bright light phase advanced, by about 90-120 min, BT(c) (P < 0.01), cortisol (P < 0.05), and melatonin (P < 0.01) rhythms. Contemporaneous administration of melatonin antagonized the phase advances of the cortisol and BT(c) rhythms, as well as the melatonin peak and melatonin offset. The phase advance of the melatonin onset was instead enhanced (P < 0.05). Contemporaneous melatonin administration modifies the capability of light to induce circadian phase shifts.

scholarly journals Clinical applications of melatonin in circadian disorders

2003 ◽  
Vol 5 (4) ◽  
pp. 399-413
Keyword(s):  
Seasonal Affective Disorder ◽  
Light Exposure ◽  
Bright Light ◽  
Circadian Phase ◽  
Delayed Sleep Phase Syndrome ◽  
Melatonin Administration ◽  
Delayed Sleep Phase ◽  
Delayed Sleep ◽  
Total Blindness ◽  
Bright Light Exposure

Chronobiological disorders and syndromes include seasonal affective disorder (SAD), total blindness, advanced and delayed sleep phase syndrome, jet lag, and shift work maladaptation. These disorders are treated by adjusting circadian phase, using appropriately timed bright light exposure and melatonin administration (at doses of 0.5 mg or less). In some cases, it may be necessary to measure internal circadían phase, using the time when endogenous melatonin levels rise.

Repeated exposures to daytime bright light increase nocturnal melatonin rise and maintain circadian phase in young subjects under fixed sleep schedule

2006 ◽  
Vol 291 (6) ◽  
pp. R1799-R1807 ◽  
Author(s):  
Nana N. Takasu ◽  
Satoko Hashimoto ◽  
Yujiro Yamanaka ◽  
Yusuke Tanahashi ◽  
Ayano Yamazaki ◽  
...  
Keyword(s):  
Body Temperature ◽  
Light Exposure ◽  
Core Body Temperature ◽  
Bright Light ◽  
Peak Level ◽  
Light Conditions ◽  
Circadian Phase ◽  
Sleep Schedule ◽  
Dim Light ◽  
Core Body

Effects of two different light intensities during daytime were examined on human circadian rhythms in plasma melatonin, core body temperature, and wrist activity under a fixed sleep schedule. Sleep qualities as indicated by polysomnography and subjective sleepiness were also measured. In the first week, under dim light conditions (∼10 lx), the onset and peak of nocturnal melatonin rise were significantly delayed, whereas the end of melatonin rise was not changed. The peak level of melatonin rise was not affected. As a result, the width of nocturnal melatonin rise was significantly shortened. In the second week, under bright light conditions (∼5,000 lx), the phases of nocturnal melatonin rise were not changed further, but the peak level was significantly increased. Core body temperature at the initial sleep phase was progressively elevated during the course of dim light exposure and reached the maximum level at the first night of bright light conditions. Subjective sleepiness gradually declined in the course of dim light exposure and reached the minimum level at the first day of bright light. These findings indicate that repeated exposures to daytime bright light are effective in controlling the circadian phase and increasing the peak level of nocturnal melatonin rise in plasma and suggest a close correlation between phase-delay shifts of the onset of nocturnal melatonin rise or body temperature rhythm and daytime sleepiness.

Nonphotic entrainment of the human circadian pacemaker

1998 ◽  
Vol 274 (4) ◽  
pp. R991-R996 ◽  
Author(s):  
Elizabeth B. Klerman ◽  
David W. Rimmer ◽  
Derk-Jan Dijk ◽  
Richard E. Kronauer ◽  
Joseph F. Rizzo ◽  
...  
Keyword(s):  
Circadian Rhythms ◽  
Light Exposure ◽  
Core Body Temperature ◽  
Biological Clock ◽  
Bright Light ◽  
Circadian Pacemaker ◽  
Temperature Rhythms ◽  
Blind Individuals ◽  
Nonphotic Entrainment ◽  
Core Body

In organisms as diverse as single-celled algae and humans, light is the primary stimulus mediating entrainment of the circadian biological clock. Reports that some totally blind individuals appear entrained to the 24-h day have suggested that nonphotic stimuli may also be effective circadian synchronizers in humans, although the nonphotic stimuli are probably comparatively weak synchronizers, because the circadian rhythms of many totally blind individuals “free run” even when they maintain a 24-h activity-rest schedule. To investigate entrainment by nonphotic synchronizers, we studied the endogenous circadian melatonin and core body temperature rhythms of 15 totally blind subjects who lacked conscious light perception and exhibited no suppression of plasma melatonin in response to ocular bright-light exposure. Nine of these fifteen blind individuals were able to maintain synchronization to the 24-h day, albeit often at an atypical phase angle of entrainment. Nonphotic stimuli also synchronized the endogenous circadian rhythms of a totally blind individual to a non-24-h schedule while living in constant near darkness. We conclude that nonphotic stimuli can entrain the human circadian pacemaker in some individuals lacking ocular circadian photoreception.

scholarly journals A single dose of alcohol does not meaningfully alter circadian phase advances and phase delays to light in humans

2016 ◽  
Vol 310 (8) ◽  
pp. R759-R765 ◽  
Author(s):  
Helen J. Burgess ◽  
Muneer Rizvydeen ◽  
Louis F. Fogg ◽  
Ali Keshavarzian
Keyword(s):  
Single Dose ◽  
Light Pulse ◽  
Bright Light ◽  
Phase Shifts ◽  
Final Phase ◽  
Circadian Timing ◽  
Circadian Phase ◽  
Sleep Episode ◽  
Late Night ◽  
Laboratory Session

Central circadian timing influences mental and physical health. Research in nocturnal rodents has demonstrated that when alcohol is consumed, it reaches the central hypothalamic circadian pacemaker (suprachiasmatic nuclei) and can directly alter circadian phase shifts to light. In two separate studies, we examined, for the first time, the effects of a single dose of alcohol on circadian phase advances and phase delays to light in humans. Two 23-day within-subjects placebo-controlled counterbalanced design studies were conducted. Both studies consisted of 6 days of fixed baseline sleep to stabilize circadian timing, a 2-day laboratory session, a 6-day break, and a repeat of 6 days of fixed sleep and a 2-day laboratory session. In the phase advance study ( n = 10 light drinkers, 24–45 yr), the laboratory sessions consisted of a baseline dim light phase assessment, sleep episode, alcohol (0.6 g/kg) or placebo, 2-h morning bright light pulse, and final phase assessment. In the phase-delay study ( n = 14 light drinkers, 22–44 yr), the laboratory sessions consisted of a baseline phase assessment, alcohol (0.8 g/kg) or placebo, 2-h late night bright light pulse, sleep episode, and final phase assessment. In both studies, alcohol either increased or decreased the observed phase shifts to light (interaction P ≥ 0.46), but the effect of alcohol vs. placebo on phase shifts to light was always on average smaller than 30 min. Thus, no meaningful effects of a single dose of alcohol vs. placebo on circadian phase shifts to light in humans were observed.

Photic resetting of intrinsic rhythmicity of the rat suprachiasmatic nucleus under various photoperiods

1998 ◽  
Vol 274 (3) ◽  
pp. R857-R863 ◽  
Author(s):  
Alena Sumová ◽  
Helena Illnerová
Keyword(s):  
Suprachiasmatic Nucleus ◽  
Dark Period ◽  
Light Exposure ◽  
Light Stimulus ◽  
Phase Shifts ◽  
Late Night ◽  
Fos Protein ◽  
Endogenous Rhythmicity ◽  
Protein Immunoreactivity ◽  
First Time

To date, photic entrainment of the mammalian circadian system has been studied by following phase shifts of overt rhythms in the periphery governed by a circadian pacemaker located in the suprachiasmatic nucleus (SCN). The present study follows for the first time photic resetting of intrinsic rhythmicity of the SCN itself. Rats maintained under either a shorter photoperiod, with 12 h of light and 12 h of darkness per day, or under a long, 18:6-h light-dark photoperiod were exposed to a light stimulus during the dark period and then released into darkness, and the next day the SCN rhythm in the light-stimulated c-Fos protein immunoreactivity was followed as a marker of the SCN endogenous rhythmicity. After a light stimulus in the early night, the evening rise in the photic elevation of Fos protein photoinduction as well as the morning decline were phase delayed within one cycle. After a light stimulus in the late night, only the morning decline in the photic elevation of Fos was phase advanced the next night, not the evening rise; consequently, the interval enabling high photic elevation of Fos was reduced. After a light stimulus was administered around the middle of the night, the next night the evening rise in the light-stimulated Fos was eventually phase delayed, the morning decline was phase advanced, and the rhythm amplitude was reduced significantly; under 18:6-h light-dark, a mere 5-min light exposure exhibited such effects. The data indicate that resetting of the SCN rhythmicity in the light-elevated c-Fos 1 day after a resetting stimulus administration, i.e., during transient cycles, may proceed via nonparallel phase shifts of the evening rise and of the morning decline of the light-stimulated Fos, and via amplitude lowering and suggest a complex circadian pacemaking system in the rat SCN.

Human circadian pacemaker is sensitive to light throughout subjective day without evidence of transients

1997 ◽  
Vol 273 (5) ◽  
pp. R1800-R1809 ◽  
Author(s):  
Megan E. Jewett ◽  
David W. Rimmer ◽  
Jeanne F. Duffy ◽  
Elizabeth B. Klerman ◽  
Richard E. Kronauer ◽  
...  
Keyword(s):  
Steady State ◽  
Response Curve ◽  
Phase Response Curve ◽  
Light Exposure ◽  
Light Stimulus ◽  
Dead Zone ◽  
Bright Light ◽  
Temperature Minimum ◽  
Circadian Pacemaker ◽  
Dim Light

Fifty-six resetting trials were conducted across the subjective day in 43 young men using a three-cycle bright-light (∼10,000 lx) stimulus against a background of very dim light (10–15 lx). The phase-response curve (PRC) to these trials was assessed for the presence of a “dead zone” of photic insensitivity and was compared with another three-cycle PRC that had used a background of ∼150 lx. To assess possible transients after the light stimulus, the trials were divided into 43 steady-state trials, which occurred after several baseline days, and 13 consecutive trials, which occurred immediately after a previous resetting trial. We found that 1) bright light induces phase shifts throughout subjective day with no apparent dead zone; 2) there is no evidence of transients in constant routine assessments of the fitted temperature minimum 1–2 days after completion of the resetting stimulus; and 3) the timing of background room light modulates the resetting response to bright light. These data indicate that the human circadian pacemaker is sensitive to light at virtually all circadian phases, implying that the entire 24-h pattern of light exposure contributes to entrainment.

scholarly journals Melatonin administration can entrain the free-running circadian system of blind subjects

2000 ◽  
Vol 164 (1) ◽  
pp. R1-R6 ◽  
Author(s):  
SW Lockley ◽  
DJ Skene ◽  
K James ◽  
K Thapan ◽  
J Wright ◽  
...  
Keyword(s):  
Circadian Rhythms ◽  
Core Body Temperature ◽  
Circadian System ◽  
Melatonin Treatment ◽  
Circadian Phase ◽  
Melatonin Administration ◽  
Free Running ◽  
Physiological Markers ◽  
Core Body ◽  
First Time

Although melatonin treatment has been shown to phase shift human circadian rhythms, it still remains ambiguous as to whether exogenous melatonin can entrain a free-running circadian system. We have studied seven blind male subjects with no light perception who exhibited free-running urinary 6-sulphatoxymelatonin (aMT6s) and cortisol rhythms. In a single-blind design, five subjects received placebo or 5 mg melatonin p.o. daily at 2100 h for a full circadian cycle (35-71 days). The remaining two subjects also received melatonin (35-62 days) but not placebo. Urinary aMT6s and cortisol (n=7) and core body temperature (n=1) were used as phase markers to assess the effects of melatonin on the During melatonin treatment, four of the seven free-running subjects exhibited a shortening of their cortisol circadian period (tau). Three of these had taus which were statistically indistinguishable from entrainment. In contrast, the remaining three subjects continued to free-run during the melatonin treatment at a similar tau as prior to and following treatment. The efficacy of melatonin to entrain the free-running cortisol rhythms appeared to be dependent on the circadian phase at which the melatonin treatment commenced. These results show for the first time that daily melatonin administration can entrain free-running circadian rhythms in some blind subjects assessed using reliable physiological markers of the circadian system.

156 Evening Light-Induced Circadian Phase Shift in Preschool-Aged Children

SLEEP ◽  
2021 ◽  
Vol 44 (Supplement_2) ◽  
pp. A63-A64
Author(s):  
Lauren Hartstein ◽  
Lameese Akacem ◽  
Cecilia Diniz Behn ◽  
Shelby Stowe ◽  
Kenneth Wright ◽  
...  
Keyword(s):  
Phase Shift ◽  
Light Exposure ◽  
Light Stimulus ◽  
Phase Delay ◽  
Healthy Children ◽  
Dependent Manner ◽  
Circadian Phase ◽  
Light Intensities ◽  
Dim Light ◽  
Dose Dependent

Abstract Introduction In adults, exposure to light at night delays the timing of the circadian clock in a dose-dependent manner with intensity. Although children’s melatonin levels are highly suppressed by evening bright light, the sensitivity of young children’s circadian timing to evening light is unknown. This research aimed to establish an illuminance response curve for phase delay in preschool children as a result of exposure to varying light intensities in the hour before bedtime. Methods Healthy children (n=36, 3.0 – 4.9 years, 39% males), participated in a 10-day protocol. For 7 days, children followed a strict parent-selected sleep schedule. On Days 8-10, an in-home dim-light assessment was performed. On Day 8, dim light melatonin onset (DLMO) was measured through saliva samples collected in 20-30-min intervals throughout the evening until 1-h past habitual bedtime. On Day 9, children were exposed to a white light stimulus (semi-randomly assigned from 5lx to 5000lx) for 1-h before their habitual bedtime, and saliva was collected before, during, and after the exposure. On Day 10, children provided saliva samples in the evening for 2.5-h past bedtime for a final DLMO assessment. Phase angle of entrainment (habitual bedtime – DLMObaseline) and circadian phase delay (DLMOfinal – DLMObaseline) were computed. Results Final DLMO (Day 10) shifted between -8 and 123 minutes (M = 56.1 +/- 33.6 min; negative value = phase advance, positive value = phase delay) compared with DLMO at baseline (Day 8). Raw phase shift did not demonstrate a dose-dependent relationship with light intensity. Rather, we observed a robust phase delay across all intensities. Conclusion These data suggest preschoolers’ circadian clocks are immensely sensitive to a large range of light intensities, which may be mechanistically influenced by less mature ophthalmologic features (e.g. clearer lenses, larger pupils). With young children’s ever-growing use of light-emitting devices and evening exposure to artificial lighting, as well as the prevalence of behavioral sleep problems, these findings may inform recommendations for parents on the effects of evening light exposure on sleep timing in early childhood. Support (if any) This research was supported with funds from the Eunice Kennedy Shriver National Institute of Child Health & Human Development (R01-HD087707).

Can short-wavelength depleted bright light during single simulated night shifts prevent circadian phase shifts?

2017 ◽  
Vol 61 ◽  
pp. 22-30 ◽  
Author(s):  
J. Regente ◽  
J. de Zeeuw ◽  
F. Bes ◽  
C. Nowozin ◽  
S. Appelhoff ◽  
...  
Keyword(s):  
Short Wavelength ◽  
Bright Light ◽  
Phase Shifts ◽  
Circadian Phase ◽  
Night Shifts
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