Season- and latitude-dependent effects of simulated twilights on circadian entrainment.

Groups of Syrian hamsters were exposed to LD cycles with twilight transitions and photoperiods simulating natural lighting conditions at the summer solstice (SS), equinox, and winter solstice (WS) at 41 degrees N and at the winter solstice at the Arctic Circle (WS 66 degrees N) but with daytime illuminance truncated at 10 lux (LD-twilight). Separate groups were kept under matching rectangular cycles (LD-rectangular). The inclusion of twilights affected several circadian parameters in a season-and latitude-dependent manner. The most striking difference was in the timing of activity onsets, which followed dusk in the presence of twilights but were more closely related to dawn (lights-on) in their absence. Activity offsets and midpoints were also earlier in LD-twilight than in LD-rectangular, with the differences being most pronounced under WS 66 degrees N. In LD-twilight, longer nights resulted in earlier offsets and midpoints, but in LD-rectangular, midpoints were later under long than under short nights while offsets did not vary significantly. In LD-twilight, activity duration (alpha) increased monotonically with increasing nighttime duration, but in LD-rectangular, alpha was shorter under WS 66 degrees N than under WS conditions. These effects of season and latitude observed in LD-twilight were similar to those reported in animals exposed to natural illumination, while those observed in LD-rectangular differed in several respects. The presence of twilights also resulted in lower day-to-day variability in activity onset times (greater precision), supporting the earlier conclusion that twilights increase the strength of the LD zeitgeber. Free-running periods in constant darkness (DD) were shorter in LD-twilight than in LD-rectangular, especially under WS 66 degrees N, raising the possibility that the effects of twilights on the timing of the entrained activity rhythm reflect their effects on the period of that rhythm. Increasing daytime illuminance to 100 lux (WS conditions only) resulted in earlier activity offsets and midpoints and a shorter alpha but had no effect on activity onsets or on subsequent period in DD. These results indicate that exposure to low twilight illuminances alone can account for several of the documented differences between the effects of natural and rectangular light cycles on circadian entrainment.

Melatonin as a hypnotic: con.

The physiological roles of melatonin are still unclear despite almost 50 years of research. Elevated melatonin levels from either endogenous nocturnal production or exogenous daytime administration are associated in humans with effects including increased sleepiness, reduced core temperature, increased heat loss and other generally anabolic physiological changes. This supports the idea that endogenous melatonin increases nocturnal sleep propensity, either directly or indirectly via physiological processes associated with sleep. The article "Melatonin as a hypnotic--Pro", also in this issue, presents evidence to support this viewpoint. We do not entirely disagree, but nevertheless feel this is an overly simplistic interpretation of the available data. Our interpretation is that melatonin is primarily a neuroendocrine transducer promoting an increased propensity for 'dark appropriate' behavior. Thus, it is our view that exogenous melatonin is only hypnotic in those species or individuals for which endogenous melatonin increases sleep propensity and is consequently a dark appropriate outcome. Evidence supporting this position is drawn primarily from studies of exogenous administration of melatonin and its varied effects on sleep/wake behavior based on dose, time of administration, age and other factors. From this perspective, it will be shown that melatonin can exert hypnotic-like effects but only under limited circumstances.

Human pineal physiology and functional significance of melatonin.

Descriptions of the pineal gland date back to antiquity, but its functions in humans are still poorly understood. In both diurnal and nocturnal vertebrates, its main product, the hormone melatonin, is synthesized and released in rhythmic fashion, during the dark portion of the day-night cycle. Melatonin production is controlled by an endogenous circadian timing system and is also suppressed by light. In lower vertebrates, the pineal gland is photosensitive, and is the site of a self-sustaining circadian clock. In mammals, including humans, the gland has lost direct photosensitivity, but responds to light via a multisynaptic pathway that includes a subset of retinal ganglion cells containing the newly discovered photopigment, melanopsin. The mammalian pineal also shows circadian oscillations, but these damp out within a few days in the absence of input from the primary circadian pacemaker in the suprachiasmatic nuclei (SCN). The duration of the nocturnal melatonin secretory episode increases with nighttime duration, thereby providing an internal calendar that regulates seasonal cycles in reproduction and other functions in photoperiodic species. Although humans are not considered photoperiodic, the occurrence of seasonal affective disorder (SAD) and its successful treatment with light suggest that they have retained some photoperiodic responsiveness. In humans, exogenous melatonin has a soporific effect, but only when administered during the day or early evening, when endogenous levels are low. Some types of primary insomnia have been attributed to diminished melatonin production, particularly in the elderly, but evidence of a causal link is still inconclusive. Melatonin administration also has mild hypothermic and hypotensive effects. A role for the pineal in human reproduction was initially hypothesized on the basis of clinical observations on the effects of pineal tumors on sexual development. More recent data showing an association between endogenous melatonin levels and the onset of puberty, as well as observations of elevated melatonin levels in both men and women with hypogonadism and/or infertility are consistent with such a hypothesis, but a regulatory role of melatonin has yet to be established conclusively. A rapidly expanding literature attests to the involvement of melatonin in immune function, with high levels promoting and low levels suppressing a number of immune system parameters. The detection of melatonin receptors in various lymphoid organs and in lymphocytes suggests multiple mechanisms of action. Melatonin has been shown to be a powerful antioxidant, and has oncostatic properties as well, both direct and indirect, the latter mediated by its effects on reproductive hormones. Finally, there are reports of abnormal daily melatonin profiles in a number of psychiatric and neurological disorders, but the significance of such abnormalities is far from clear.

Effects of an afternoon nap on nighttime alertness and performance in long-haul drivers.

The effects of an afternoon nap on alertness and psychomotor performance were assessed during a simulated night shift. After a night of partial sleep restriction, eight professional long-haul drivers either slept (nap condition) or engaged in sedentary activities (no-nap condition) from 14:00 to 17:00 h. Alertness and performance testing sessions were conducted at 12:00 (pre-nap baseline), 24:00, 02:30, 05:00 and 07:30 h, and followed 2-h runs in a driving simulator. In the nap condition, the subjects showed lower subjective sleepiness and fatigue, as measured by visual analog scales, and faster reaction times and less variability on psychomotor performance tasks. Electrophysiological indices of arousal during the driving runs also reflected the beneficial effects of the afternoon nap, with lower spectral activity in the theta (4-7.75 Hz), alpha (8-11.75 Hz) and fast theta-slow alpha (6-9.75 Hz) frequency bands of the electroencephalogram, indicating higher arousal levels. Thus, a 3-h napping opportunity ending at 17:00 h improved significantly several indices of alertness and performance measured 7-14 h later.

Light visor treatment for jet lag after westward travel across six time zones.

INTRODUCTION: The aim of this field study was to evaluate the efficacy of a light treatment for jet lag, using a head-mounted light visor, following a westward flight across six time zones. METHODS: There were 20 subjects who were exposed to bright white light (3000 lux) or dim red light (10 lux) for 3 h on the first two evenings after a flight from Zurich to New York. Salivary dim light melatonin onset (DLMO), assessed 2 d before and 2 d after the flight, provided a measure of circadian phase. Sleep was recorded by actigraphy, while post-flight performance testing and subjective scales provided additional indices of jet lag severity. RESULTS: The DLMO measurements showed a larger phase delay in the bright light than in the dim light group (2.59 h vs. 1.58 h, p < 0.02). There was no overall difference in sleep efficiency (SE) between the two groups, but a significant Group x Night interaction reflected a small increase across the first two post-flight nights in the bright light group, and a small decrease in the dim light group. Reaction time on one of two performance tests was consistently faster in the dim light group, but was unrelated to circadian phase or to prior sleep. There were no major group differences in subjective sleep quality, daytime sleepiness, jet lag severity, or mood. DISCUSSION: This is the first full-scale study to show that bright light treatment can accelerate circadian reentrainment following transmeridian travel. However, the effect on reentrainment rate was modest, and was not accompanied by any improvement in sleep, performance, or subjective assessments of jet lag symptoms.

Twilights widen the range of photic entrainment in hamsters.

The range of entrainment of the circadian rhythm of locomotor activity was compared in four groups of Syrian hamsters (eight animals per group) initially exposed to daily light-dark (LD) cycles with either abrupt transitions between light and darkness (LD-rectangular) or simulated twilights (LD-twilight). Lighting was provided by arrays of white light-emitting diodes; daytime illuminance (10 lux) and the total amount of light emitted per day were the same in the two conditions. The period (T) of the LD cycles was then gradually increased to 26.5 h or gradually decreased to 21.5 h, at the rate of 5 min/day. Under LD-rectangular, the upper and lower limits of entrainment were 25.0 to 25.5 h and 22.0 to 22.5 h, respectively, whereas under LD-twilight, 50% of the animals exposed to the lengthening cycles were still entrained at T = 26.5 h and 50% of those exposed to the shortening cycles were still entrained at T = 21.5 h. In a second experiment, two groups of hamsters were exposed to fixed T = 25 h LD-rectangular (n = 15) or LD-twilight cycles (n = 7). Only 33% of the animals entrained in LD-rectangular, whereas 86% of the animals entrained in LD-twilight. Free-running periods in constant darkness were longer following successful entrainment to T = 25 h but did not differ between the animals that entrained to LD-rectangular and those that entrained to LD-twilight. The widening of the range of entrainment observed in LD-twilight indicates that twilight transitions increase the strength of the LD zeitgeber. In LD-twilight, successful entrainment to T = 26.5 h was accompanied by an expansion of activity time to 16.52+/-1.22 h, with activity onsets preceding mid-dusk by 12.56+/-2.15 h. Together with earlier data showing similar phase response curves for hour-long dawn, dusk, and rectangular light pulses, these results suggest that the effect of twilights on the range of entrainment may involve parametric rather than nonparametric mechanisms.