Quantal melatonin suppression by exposure to low intensity light in man

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

Nasal versus temporal illumination of the human retina: effects on core body temperature, melatonin, and circadian phase

The mammalian retina contains both visual and circadian photoreceptors. In humans, nocturnal stimulation of the latter receptors leads to melatonin suppression, which might cause reduced nighttime sleepiness. Melatonin suppression is maximal when the nasal part of the retina is illuminated. Whether circadian phase shifting in humans is due to the same photoreceptors is not known. The authors explore whether phase shifts and melatonin suppression depend on the same retinal area. Twelve healthy subjects participated in a within-subjects design and received all of 3 light conditions--1) 10 lux of dim light on the whole retina, 2) 100 lux of ocular light on the nasal part of the retina, and 3) 100 lux of ocular light on the temporal part of the retina--on separate nights in random order. In all 3 conditions, pupils were dilated before and during light exposure. The protocol consisted of an adaptation night followed by a 23-h period of sustained wakefulness, during which a 4-h light pulse was presented at a time when maximal phase delays were expected. Nasal illumination resulted in an immediate suppression of melatonin but had no effect on subjective sleepiness or core body temperature (CBT). Nasal illumination delayed the subsequent melatonin rhythm by 78 min, which is significantly (p= 0.016) more than the delay drift in the dim-light condition (38 min), but had no detectable phase-shifting effect on the CBT rhythm. Temporal illumination suppressed melatonin less than the nasal illumination and had no effect on subjective sleepiness and CBT. Temporal illumination delayed neither the melatonin rhythm nor the CBT rhythm. The data show that the suppression of melatonin does not necessarily result in a reduction of subjective sleepiness and an elevation ofCBT. In addition, 100 lux of bright white light is strong enough to affect the photoreceptors responsible for the suppression of melatonin but not strong enough to have a significant effect on sleepiness and CBT. This may be due to the larger variability of the latter variables.     

Systematic review of light exposure impact on human circadian rhythm

Light is necessary for life, and artificial light improves visual performance and safety, but there is an increasing concern of the potential health and environmental impacts of light. Findings from a number of studies suggest that mistimed light exposure disrupts the circadian rhythm in humans, potentially causing further health impacts. However, a variety of methods has been applied in individual experimental studies of light-induced circadian impacts, including definition of light exposure and outcomes. Thus, a systematic review is needed to synthesize the results. In addition, a review of the scientific evidence on the impacts of light on circadian rhythm is needed for developing an evaluation method of light pollution, i.e., the negative impacts of artificial light, in life cycle assessment (LCA). The current LCA practice does not have a method to evaluate the light pollution, neither in terms of human health nor the ecological impacts. The systematic literature survey was conducted by searching for two concepts: light and circadian rhythm. The circadian rhythm was searched with additional terms of melatonin and rapid-eye-movement (REM) sleep. The literature search resulted to 128 articles which were subjected to a data collection and analysis. Melatonin secretion was studied in 122 articles and REM sleep in 13 articles. The reports on melatonin secretion were divided into studies with specific light exposure (101 reports), usually in a controlled laboratory environment, and studies of prevailing light conditions typical at home or work environments (21 studies). Studies were generally conducted on adults in their twenties or thirties, but only very few studies experimented on children and elderly adults. Surprisingly many studies were conducted with a small sample size: 39 out of 128 studies were conducted with 10 or less subjects. The quality criteria of studies for more profound synthesis were a minimum sample size of 20 subjects and providing details of the light exposure (spectrum or wavelength; illuminance, irradiance or photon density). This resulted to 13 qualified studies on melatonin and 2 studies on REM sleep. Further analysis of these 15 reports indicated that a two-hour exposure to blue light (460 nm) in the evening suppresses melatonin, the maximum melatonin-suppressing effect being achieved at the shortest wavelengths (424 nm, violet). The melatonin concentration recovered rather rapidly, within 15 min from cessation of the exposure, suggesting a short-term or simultaneous impact of light exposure on the melatonin secretion. Melatonin secretion and suppression were reduced with age, but the light-induced circadian phase advance was not impaired with age. Light exposure in the evening, at night and in the morning affected the circadian phase of melatonin levels. In addition, even the longest wavelengths (631 nm, red) and intermittent light exposures induced circadian resetting responses, and exposure to low light levels (5–10 lux) at night when sleeping with eyes closed induced a circadian response. The review enables further development of an evaluation method of light pollution in LCA regarding the light-induced impacts on human circadian system.     

Melatonin suppression by light in humans is maximal when the nasal part of the retina is illuminated

This study investigated whether sensitivity of the nocturnal melatonin suppression response to light depends on the area of the retina exposed. The reason to suspect uneven spatial sensitivity distribution stems from animal work that revealed that retinal ganglion cells projecting to the suprachiasmatic nuclei (SCN) are unequally distributed in several species of mammals. Four distinct areas of the retinas of 8 volunteers were selectively exposed to 500 lux between 1:30 a.m. and 3:30 a.m. Saliva samples were taken before, during, and after light exposure in 1-h intervals. A significant difference in sensitivity was found between exposure of the lateral and nasal parts of the retinas, showing that melatonin suppression is maximal on exposure of the nasal part of the retina. The results imply that artificial manipulation of the circadian pacemaker to alleviate jet lag, to improve alertness in shift workers, and possibly to treat patients suffering from seasonal affective disorder should encompass light exposure of the nasal retina.     

Psychophysiological effects of a brief nocturnal light exposure

This study compared the effects of a brief pulse (60-minute) of three full spectrum light intensities (1000, 500 and 30 lux) and two green light intensities (1000 and 500 lux) administered between 0200 and 0300 hrs. Ten participants were involved in this repeated measures study. Each participant experienced one condition every week for five weekends. Sessions began at 1800 hours and ended at 0600 hours the following day. Outside of the 60-minute exposure period, each session was spent in 30 lux white light. Oral temperature, salivary melatonin, cognitive performance and subjective mood were sampled throughout the sessions. Analysis revealed that all of the experimental light conditions significantly reduced salivary melatonin concentrations immediately following the pulse. This effect was not maintained beyond the duration of the light pulse. There was no significant effect on oral temperature. There were also no significant effects on cognitive performance and subjective mood, though some positive trends were observed. These results argue that brief, moderate intensity, pulses of either green or full spectrum light are sufficient to suppress the normal nocturnal rise in melatonin. However, the level of suppression obtained does not translate into significant improvement in cognitive performance or subjective mood.     

No melatonin suppression by illumination of popliteal fossae or eyelids

A recent report that popliteal illumination shifted the circadian rhythms of body temperature and melatonin challenged the longstanding belief that light phase-shifting the circadian system in mammals is mediated only through the retina. The authors tested effects of popliteal illumination and illumination provided through the eyelids on melatonin suppression. In randomized, counterbalanced orders, healthy volunteers received three treatments from midnight until 2:00 AM, one on each of three visits to the laboratory. Treatments included (1) no illumination from light pads applied to the popliteal fossae, with light mask maintained at < 3 lux (control); (2) light mask illuminated at 1700 lux, with popliteal light pads extinguished; and (3) popliteal light pads illuminated (13,000 lux) and light mask at < 3 lux (control). Saliva specimens were sampled at midnight, at 1:00 AM, and at 2:00 AM. Mean salivary melatonin concentrations rose from an average of 30.8 (3.9) pg/ml at midnight (baseline), to 33.2 (4.0) pg/ml at 1:00 AM, and to 37.2 (3.8) pg/ml at 2:00 AM in all three conditions, but no statistical differences were found using repeated-measures ANOVA. No evidence of melatonin suppression by either popliteal or closed eyelid light stimulation was found. These data suggest that bright retinal illumination is necessary for suppression of melatonin mediated through the suprachiasmatic nuclei.     

INCREASED SENSITIVITY TO LIGHT-INDUCED MELATONIN SUPPRESSION IN PREMENSTRUAL DYSPHORIC DISORDER

Increased sensitivity to light-induced melatonin suppression characterizes some, but not all, patients with bipolar illness or seasonal affective disorder. The aim of this study was to test the hypothesis that patients with premenstrual dysphoric disorder (PMDD), categorized as a depressive disorder in Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV), have altered sensitivity to 200 lux light during mid-follicular (MF) and late-luteal (LL) menstrual cycle phases compared with normal control (NC) women. As an extension of a pilot study in which the authors administered 500 lux to 8 PMDD and 5 NC subjects, in the present study the authors administered 200 lux to 10 PMDD and 13 NC subjects during MF and LL menstrual cycle phases. Subjects were admitted to the General Clinical Research Center (GCRC) in dim light (<50 lux) to dark (during sleep) conditions at 16:00?h where nurses inserted an intravenous catheter at 17:00?h and collected plasma samples for melatonin at 30-min intervals from 18:00 to 10:00?h, including between 00:00 and 01:00?h for baseline values, between 01:30 and 03:00?h during the 200 lux light exposure administered from 01:00 to 03:00?h, and at 03:30 and 04:00?h after the light exposure. Median % melatonin suppression was significantly greater in PMDD (30.8%) versus NC (?0.2%) women (p?=?.040), and was significantly greater in PMDD in the MF (30.8%) than in the LL (?0.15%) phase (p?=?.047). Additionally, in the LL (but not the MF) phase, % suppression after 200 lux light was significantly positively correlated with serum estradiol level (p ?=? .007) in PMDD patients, but not in NC subjects (p?>?.05). (Author correspondence: bparry@ucsd.edu)     

The circadian response of intrinsically photosensitive retinal ganglion cells

Intrinsically photosensitive retinal ganglion cells (ipRGC) signal environmental light level to the central circadian clock and contribute to the pupil light reflex. It is unknown if ipRGC activity is subject to extrinsic (central) or intrinsic (retinal) network-mediated circadian modulation during light entrainment and phase shifting. Eleven younger persons (18-30 years) with no ophthalmological, medical or sleep disorders participated. The activity of the inner (ipRGC) and outer retina (cone photoreceptors) was assessed hourly using the pupil light reflex during a 24 h period of constant environmental illumination (10 lux). Exogenous circadian cues of activity, sleep, posture, caffeine, ambient temperature, caloric intake and ambient illumination were controlled. Dim-light melatonin onset (DLMO) was determined from salivary melatonin assay at hourly intervals, and participant melatonin onset values were set to 14 h to adjust clock time to circadian time. Here we demonstrate in humans that the ipRGC controlled post-illumination pupil response has a circadian rhythm independent of external light cues. This circadian variation precedes melatonin onset and the minimum ipRGC driven pupil response occurs post melatonin onset. Outer retinal photoreceptor contributions to the inner retinal ipRGC driven post-illumination pupil response also show circadian variation whereas direct outer retinal cone inputs to the pupil light reflex do not, indicating that intrinsically photosensitive (melanopsin) retinal ganglion cells mediate this circadian variation.     

Nonvisual responses to light exposure in the human brain during the circadian night

The brain processes light information to visually represent the environment but also to detect changes in ambient light level. The latter information induces non-image-forming responses and exerts powerful effects on physiology such as synchronization of the circadian clock and suppression of melatonin. In rodents, irradiance information is transduced from a discrete subset of photosensitive retinal ganglion cells via the retinohypothalamic tract to various hypothalamic and brainstem regulatory structures including the hypothalamic suprachiasmatic nuclei, the master circadian pacemaker. In humans, light also acutely modulates alertness, but the cerebral correlates of this effect are unknown. We assessed regional cerebral blood flow in 13 subjects attending to auditory and visual stimuli in near darkness following light exposures (>8000 lux) of different durations (0.5, 17, 16.5, and 0 min) during the biological night. The bright broadband polychromatic light suppressed melatonin and enhanced alertness. Functional imaging revealed that a large-scale occipito-parietal attention network, including the right intraparietal sulcus, was more active in proportion to the duration of light exposures preceding the scans. Activity in the hypothalamus decreased in proportion to previous illumination. These findings have important implications for understanding the effects of light on human behavior.     

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

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

Endothelin receptors in light-induced retinal degeneration

Excessive light exposure leads to retinal degeneration in albino animals and exacerbates the rate of photoreceptor apoptosis in several retinal diseases. In previous studies we have described the presence of endothelin-1 (ET-1) and its receptors (ET-A and ET-B) in different sites of the mouse retina, including the retinal pigment epithelium, the outer plexiform layer (OPL), astrocytes, the ganglion cell layer (GCL), and vascular endothelia. After light-induced degeneration of photoreceptors, endothelinergic structures disappear from the OPL, but ET-1 and ET-B immunoreactivities increase in astrocytes. Here, we present novel observations about the course of light-induced retinal degeneration in BALB-c mice exposed to 1500 lux during 4 days with or without treatment with tezosentan, a mixed endothelinergic antagonist. Retinal whole mounts were immunostained with anticleaved caspase-3 (CC-3) serum to identify apoptotic photoreceptor cells within the outer nuclear layer (ONL). Glial activation was measured as glial fibrillary acidic protein (GFAP) immunoreactivity in retinal whole mounts and in Western blots from retinal extracts. Tezosentan treatment significantly reduced both the number of CC3-immunoreactive cells and GFAP levels, suggesting that inhibition of endothelinergic receptors could play a role in photoreceptor survival. Using confocal double immunofluorescence, we have observed that ET-A seems to be localized in bipolar cell dendrites, whereas ET-B is localized in horizontal cells. Our observations suggest the existence of an endothelinergic mechanism modulating synaptic transmission in the OPL. This mechanism could perhaps explain the effects of tezosentan treatment on photoreceptor survival.     

Light-emitting diodes and cool white fluorescent light similarly suppress pineal gland melatonin and maintain retinal function and morphology in the rat.

BACKGROUND AND PURPOSE: A novel light-emitting diode (LED) light source for use in animal-habitat lighting was evaluated. METHODS: The LED was evaluated by comparing its effectiveness with that of cool white fluorescent light (CWF) in suppressing pineal gland melatonin content and maintaining normal retinal physiology, as evaluated by use of electroretinography (ERG), and morphology. RESULTS: Pineal melatonin concentration was equally suppressed by LED and CWF light at five light illuminances (100, 40, 10, 1, and 0.1 lux). There were no significant differences in melatonin suppression between LED and CWF light, compared with values for unexposed controls. There were no differences in ERG a-wave implicit times and amplitudes or b-wave implicit times and amplitudes between 100-lux LED-exposed rats and 100-lux CWF-exposed rats. Results of retinal histologic examination indicated no differences in retinal thickness, rod outer segment length, and number of rod nuclei between rats exposed to 100-lux LED and 100-lux CWF for 14 days. Furthermore, in all eyes, the retinal pigmented epithelium was intact and not vacuolated, whereas rod outer segments were of normal thickness. CONCLUSION: LED light does not cause retinal damage and can suppress pineal melatonin content at intensities similar to CWF light intensities.     

Variations in the light-induced suppression of nocturnal melatonin with special reference to variations in the pupillary light reflex in humans

The purpose of the present study was to elucidate the existence of individual differences of pupil response to light stimulation, and to confirm the reproducibility of this phenomenon. Furthermore, the relationship between the individual differences in nocturnal melatonin suppression induced by lighting and the individual differences of pupillary light response (PLR) was examined. The pupil diameter and salivary melatonin content of 20 male students were measured at the same period of time (00:00-02:30 hr) on different days, accordingly. Illumination (530 nm) produced by a monochromatic light-emitting diode (LED) was employed as the light stimulation: pupil diameter was measured with 4 different levels of illuminance of 1, 3, 30 and 600 lux and melatonin levels were measured at 30 and 600 lux (respective controls were taken at 0 lux). Oral temperature, blood pressure and subjective index of sleepiness were taken in experiments where melatonin levels were measured. Changes of the pupil diameter in response to light were expressed as PLR and light-induced melatonin suppression was expressed as a control-adjusted melatonin suppression score (control-adjusted MSS), which was compared to the melatonin level measured at 0 lux. In the PLR, the coefficients of variation obtained at 30 lux or less were large (51.5, 45.0, 28.4 and 6.2% at 1, 3, 30 and 600 lux, respectively). Correlations of illuminance of any combination at 30 lux or less were statistically significant at less than 1% level (1 vs. 3 lux: r=0.68; 1 vs. 30 lux: r=0.64; 3 vs. 30 lux: r=0.73), which showed the reproducibility of individual differences. The control-adjusted MSS at 600 lux (-1.14+/-1.16) was significantly (p<0.05) lower than that registered at 30 lux (-0.22+/-2.12). PLR values measured at 30 and 600 lux were then correlated with control-adjusted MSS; neither indicated a significant linear relationship. However, the control-adjusted MSS showed around 0 under any of the illuminance conditions in subjects with high PLR. In control-adjusted MSS of low values (i.e., melatonin secretions were easily suppressed), subjects indicated typically low PLR. In subjects with low control-adjusted MSS (n=3), characteristic changes in the autonomic nervous system, such as body temperature and blood pressure, were noted in subjects exposed to low illuminance of 30 lux. The fact that the relationship between PLR and control-adjusted MSS portray a similar pattern even under different luminance conditions suggests that MSS may not be affected in those with high PLR at low illuminance, regardless of the illuminance condition.     

Retinotopic Distribution of Structural and Functional Damages following Bright Light Exposure of Juvenile Rats

In the present study, we aimed at better understanding the short (acute) and long term (chronic) degenerative processes characterizing the juvenile rat model of light-induced retinopathy. Electroretinograms, visual evoked potentials (VEP), retinal histology and western blots were obtained from juvenile albino Sprague-Dawley rats at preselected postnatal ages (from P30 to P400) following exposure to 10,000 lux from P14 to P28. Our results show that while immediately following the cessation of exposure, photoreceptor degeneration was concentrated within a well delineated area of the superior retina (i.e. the photoreceptor hole), with time, this hole continued to expand to form an almost photoreceptor-free region covering most of superior-inferior axis. By the end of the first year of life, only few photoreceptors remained in the far periphery of the superior hemiretina. Interestingly, despite a significant impairment of the outer retinal function, the retinal output (VEP) was maintained in the early phase of this retinopathy. Our findings thus suggest that postnatal exposure to a bright luminous environment triggers a degenerative process that continues to impair the retinal structure and function (mostly at the photoreceptor level) long after the cessation of the exposure regimen (more than 1 year documented herein). Given the slow degenerative process triggered following postnatal bright light exposure, we believe that our model represents an attractive alternative (to other more genetic models) to study the pathophysiology of photoreceptor-induced retinal degeneration as well as therapeutic strategies to counteract it.     

Entrainment of Circadian Programs

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

Wavelength-dependent effects of evening light exposure on sleep architecture and sleep EEG power density in men

Light strongly influences the circadian timing system in humans via non-image-forming photoreceptors in the retinal ganglion cells. Their spectral sensitivity is highest in the short-wavelength range of the visible light spectrum as demonstrated by melatonin suppression, circadian phase shifting, acute physiological responses, and subjective alertness. We tested the impact of short wavelength light (460 nm) on sleep EEG power spectra and sleep architecture. We hypothesized that its acute action on sleep is similar in magnitude to reported effects for polychromatic light at higher intensities and stronger than longer wavelength light (550 nm). The sleep EEGs of eight young men were analyzed after 2-h evening exposure to blue (460 nm) and green (550 nm) light of equal photon densities (2.8 x 10(13) photons x cm(-2) x s(-1)) and to dark (0 lux) under constant posture conditions. The time course of EEG slow-wave activity (SWA; 0.75-4.5 Hz) across sleep cycles after blue light at 460 nm was changed such that SWA was slightly reduced in the first and significantly increased during the third sleep cycle in parietal and occipital brain regions. Moreover, blue light significantly shortened rapid eye movement (REM) sleep duration during these two sleep cycles. Thus the light effects on the dynamics of SWA and REM sleep durations were blue shifted relative to the three-cone visual photopic system probably mediated by the circadian, non-image-forming visual system. Our results can be interpreted in terms of an induction of a circadian phase delay and/or repercussions of a stronger alerting effect after blue light, persisting into the sleep episode.     

Interactions between light and melatonin on the circadian clock of mice.

Melatonin and light synchronize the biological clock and are used to treat sleep/wake disturbances in humans. However, the two treatments affect circadian rhythms differently when they are combined than when they are administered individually. To elucidate the nature of the interaction between melatonin and light, the present study assessed the effect of melatonin on circadian timing and immediate-early gene expression in the suprachiasmatic nucleus (SCN) when administered in the presence of light. Male C3H/HeN mice, housed in constant dark in cages equipped with running wheels, were treated with either melatonin (90 microg, s.c.) or vehicle (3% ethanol-saline) 5 min prior to exposure to light (15 min, 300 lux) at various times in the circadian cycle. Combined treatment resulted in lower magnitude phase delays of circadian activity rhythms than those obtained with light alone during the early subjective night and advances in phase when melatonin and light were administered during the subjective day (p < .001). The reduction in phase delays with combined treatment at Circadian Time (CT) 14 was significant when light exposure measured 300 lux but not at lower light levels (p < .05). When light preceded melatonin administration, the inhibition of phase delays attained significance only when the light exposure reached 1000 lux (p < .05). Neither basal nor light-induced expression of c-fos mRNA in the SCN was modified by melatonin administration at CT 14 or CT 22. Together, these results suggest that combined administration of melatonin and light affect circadian timing in a manner not predicted by summing the two treatments given individually. Furthermore, the interaction is not likely to be due to inhibition of photic input to the clock by melatonin but might arise from a photically induced enhancement of melatonin's actions on circadian timing.     

Illumination of upper and middle visual fields produces equivalent suppression of melatonin in older volunteers

Bright light treatment has become an important method of treating depression and circadian rhythm sleep disorders. The efficacy of bright light treatment may be dependent upon the position of the light-source, as it determines the relative illumination in each portion of the visual field. This study compared illumination of upper and middle visual fields to determine whether melatonin suppression is different or equivalent. Thirteen older volunteers received three illumination conditions in counterbalanced orders: 1000 lux in the upper visual field, 1000 lux in the middle visual field, or dim diffuse illumination < 5 lux. A four-choice reaction time task was performed during tests to ensure eye direction and illumination of the intended portion of the visual field. Illumination in the upper and middle visual fields significantly suppressed melatonin compared to < 5 lux (p < 0.001). Melatonin suppression was not significantly different with upper or middle field illumination. These results indicate that bright light treatments placed above the eye level might be as effective as those requiring patients to look directly at the light source. Clinical comparative testing would be valuable. In addition, this study demonstrates that significant suppression of melatonin may be achieved through the use of bright light in healthy older volunteers.     

The Test Re-Test Reliability of the Melatonin Suppression by White Light

The melatonin supersensitivity to light has been suggested as a biological marker of bipolar disorder. However previous studies have been inconsistent with regard to light induced suppression of melatonin and raising questions regarding its reproducibility and reliability. The present study examined the test re-test reliability of the melatonin suppression by light in healthy subjects. Study was divided into two parts. The first examined the melatonin suppression by 200 lux of light while the second examined effect 500 lux of light. Subjects were tested twice, separated by one week for each part of the study. On each night subjects reported to the study at 1800 h. The first sample was collected at 2100 h (in the light). Subjects were then placed in a dark room, with a background light intensity of 10–20 lux. Further blood samples were collected at regular intervals. After each collection, blood samples were centrifuged and plasma separated and stored frozen at –20ºC. Plasma melatonin concentrations were determined by a specific radioimmunoassay. Results showed poor test re-test reliability for nights 1 and 2 for both light intensities suggesting that the melatonin suppression by light is not reproducible and has poor reliability. The poor test re-test reliability may provide an explanation for the inconsistencies in previous studies.     

The Test Re-Test Reliability of the Melatonin Suppression by White Light

The melatonin supersensitivity to light has been suggested as a biological marker of bipolar disorder. However previous studies have been inconsistent with regard to light induced suppression of melatonin and raising questions regarding its reproducibility and reliability. The present study examined the test re-test reliability of the melatonin suppression by light in healthy subjects. Study was divided into two parts. The first examined the melatonin suppression by 200 lux of light while the second examined effect 500 lux of light. Subjects were tested twice, separated by one week for each part of the study. On each night subjects reported to the study at 1800 h. The first sample was collected at 2100 h (in the light). Subjects were then placed in a dark room, with a background light intensity of 10-20 lux. Further blood samples were collected at regular intervals. After each collection, blood samples were centrifuged and plasma separated and stored frozen at -20ºC. Plasma melatonin concentrations were determined by a specific radioimmunoassay. Results showed poor test re-test reliability for nights 1 and 2 for both light intensities suggesting that the melatonin suppression by light is not reproducible and has poor reliability. The poor test re-test reliability may provide an explanation for the inconsistencies in previous studies.