Effects of daytime ingestion of melatonin on short-term athletic performance.

The immediate effects of ingesting melatonin in the daytime include decreased alertness and body temperature. To date, no researcher has examined whether daytime ingestion of melatonin leads to impairments in variables relevant to short-term (<10 min) athletic performance. Twelve physically active participants (mean +/- s age = 25.2 +/- 5.0 years, body mass = 81.4 +/- 12.1 kg and chronotype = 33.8 +/- 6.3 units) ingested 5 mg of melatonin or placebo at 11:45 hours in a double-blind experiment. At 13:00 and 17:00 hours, subjective alertness was measured, together with intra-aural temperature, reaction time (two-, four- and eight-choice), short-term memory recall and grip strength. Performance, ratings of perceived exertion (RPE) and heart rate were also recorded during a 4-km cycling time trial. At 13:00 hours, the mean +/- s intra-aural temperature was 0.49 +/- 0.79 degrees C lower after ingestion of melatonin than after placebo (p = 0.015), but this difference was not apparent at 17:00 hours. At both 13:00 and 17:00 hours, melatonin reduced (p < 0.05) alertness, short-term memory and exercise heart rate by 1.5 +/- 1.8 units, 1 +/- 1 digits and 6 +/- 9 beats.min(-1), respectively (mean +/- s). Eight-choice reaction time was also slower at both times of day after ingesting melatonin. Melatonin did not influence time trial performance or RPE (p > 0.05). The effects of 5 mg of melatonin seem more pronounced for mental rather than physical components of short-term athletic performance, although the cardiovascular responses to exercise are affected. Some effects of melatonin were apparent 5 h after ingestion when the hypothermic effects of melatonin had dissipated.

Coupled biological oscillators in a cave insect.

Insects that live in the interior of caves show the basic internal temporal organization of coupled oscillators. An analysis is made of the coupled moulting and oviposition cycles of Folsomia candida, a cave-dwelling Collembolan, with regard to their oscillatory nature, their phase dependent responses to external perturbations, the effect of coupling on these responses, and conjecture about the link of these cycles with circadian clocks in other organisms.

Complex interaction of the sleep-wake cycle and circadian phase modulates mood in healthy subjects.

BACKGROUND: Several studies of healthy volunteers have revealed that subjective mood may vary with the duration of prior wakefulness and with the time of day. However, in these studies, the effects of extended wakefulness and circadian phase remained confounded, and the interaction of these 2 processes could not be assessed quantitatively. METHODS: In the present study, a total of 24 healthy young subjects (16 men, 8 women) lived on a 30-hour sleep-wake schedule for 19 to 23 days or on a 28-hour sleep-wake schedule for 33 to 36 days; both schedules induced desynchrony between the subjects' sleep-wake cycle and their endogenous circadian pacemaker. Subjective mood was assessed by 2 types of visual analog scales, which were administered twice every 2 hours and every 20 minutes, respectively, during all scheduled wakefulness episodes. A circadian phase and an interval elapsed since awakening were attributed to each data point, and circadian and wake-dependent fluctuations of mood were assessed. RESULTS: A significant variation of mood with circadian phase was observed, but no reliable main effect of the duration of prior wakefulness was found. A statistically significant interaction of circadian and wake-dependent fluctuations was evident; when the analysis was restricted to specific circadian phases, mood improved, deteriorated, or remained stable with the duration of prior wakefulness. CONCLUSIONS: These results indicate that, in healthy young subjects, subjective mood is influenced by a complex and nonadditive interaction of circadian phase and duration of prior wakefulness. The nature of this interaction is such that moderate changes in the timing of the sleep-wake cycle may have profound effects on subsequent mood.

Interpersonal sensitivity predicts depressive symptom response to the circadian rhythm disruption of nightwork.

This paper reports the results of a study designed to explore the validity of a shiftwork model of affective disorders. Fifty-five student nurses doing nightwork for the first time were recruited to a study designed both to replicate an earlier study of the effects of nightwork on cognitive, emotional and neurovegetative measures and to assess the effects of nightwork on personality measures and the role of personality factors and nightwork induced disturbances in predicting accommodation to nightwork. As in the earlier study, concentration, interest, energy, sleep and appetite were significantly disturbed by nightwork and there was an increased perception of recent criticism from other. The findings from both studies were, therefore, aggregated to explore further possible relations between outcomes and the pre-nightwork level of affective symptoms and sensitivity to interpersonal criticism. These predicted poor response. In contrast, measures of cognitive style and symptom interpretation did not predict outcome. The findings are not inconsistent with proposals that disturbance of circadian rhythms consequent on psychosocial disruptions may play a part in the genesis of or maintenance of depression. They also support a proposal that nightwork induced changes may be a suitable human model for investigation of aspects of the affective disorders.

The shape of the endogenous circadian rhythm of rectal temperature in humans.

Fourteen healthy subjects have been studied in an isolation unit while living on a 30h "day" (20h awake, 10h asleep) for 14 (solar) days but while aware of real time. Waking activities were sedentary and included reading, watching television, and so forth. Throughout, regular recordings of rectal temperature were made, and in a subgroup of 6 subjects, activity was measured by a wrist accelerometer. Temperature data have been subjected to cosinor analysis after "purification," a method that enables the endogenous (clock-drive) and exogenous (activity-driven) components of the circadian rhythm to be assessed. Moreover, the protocol enables effects due to the circadian rhythm and time-since-waking to be separated. Results showed that the masking effects on body temperature exerted by the exogenous factors appeared to be less than average in the hours before and just after the peak of the endogenous temperature rhythm. This has the effect of producing a temperature plateau rather than a peak during the daytime. The implications of this for mental performance and sleep initiation are discussed.

Circadian rhythms in renal function in hypertensive TGR(mRen-2)27 rats and their normotensive controls.

Patients with secondary hypertension frequently display abnormal circadian blood pressure profiles, characterized by a failure to decrease blood pressure at night. The transgenic TGR(mRen-2)27 rat strain, developing fulminant hypertension after the mouse salivary Ren-2 renin gene has been integrated into its genome, provides a fundamental model of genetic hypertension. Because of an inverse circadian blood pressure profile and an unchanged rhythmic pattern of heart rate compared with the normotensive Sprague-Dawley (SPR) strain, it was proposed to serve as an animal model of genetic hypertension. It was the aim of the present study to investigate the circadian rhythmicity in renal function of the transgenic rat to determine whether hypertension and disturbed circadian blood pressure profile would affect kidney function. Urinary water, electrolyte, and protein excretion, as well as glomerular filtration rate and renal plasma flow, were determined in unrestrained freely moving transgenic hypertensive (TGR) and SPR normotensive control rats by collecting urine and arterial blood every 4 h. Significant and similar circadian rhythms were found in renal excretion and hemodynamics in both normotensive and hypertensive strains. Peaks occurred in the active dark period, whereas troughs were found in daytime for all parameters. However, it has to be pointed out that, although the circadian profiles were not grossly perturbed in hypertensive animals, some small differences between SPR and TGR strains did exist in renal function. These discrepancies were precisely related to acrophase, showing a slight phase delay, and also to relative amplitude in TGR. This study demonstrates that the inverted circadian blood pressure profile affected only slightly the circadian rhythms in kidney function in TGR compared with SPR. These findings support the notion that time-dependent changes in systemic blood flow may be of greater importance for circadian regulation of kidney function than systemic blood pressure.

Circadian rhythms in the neonate and in old age: what do they tell us about the development and decay of the body clock in humans?

This overview describes changes in human circadian rhythms in the neonate and in aged subjects. Since a measured circadian rhythm is derived from an endogenous (clock-driven) component and an exogenous component (due to rhythms in the environment and lifestyle), this account attempts to separate these possibilities in any particular case. Experimental methods for distinguishing between these components are described, and it is concluded that the data are rarely clear enough for such distinctions in mechanism to be made with confidence. Nevertheless, the evidence to date suggests that changes to the endogenous and exogenous components during both the development and decay of circadian rhythms are involved. This being the case, and accepting that poorly developed circadian rhythms are often associated with poor general health and development, methods to strengthen circadian rhythms are described.

Circadian rhythms in the neonate and in old age: what do they tell us about the development and decay of the body clock in humans?

This overview describes changes in human circadian rhythms in the neonate and in aged subjects. Since a measured circadian rhythm is derived from an endogenous (clock-driven) component and an erogenous component (due to rhythms in the environment and lifestyle), this account attempts to separate these possibilities in any particular case. Experimental methods for distinguishing between these components are described, and it is concluded that the data are rarely clear enough for such distinctions in mechanism to be made with confidence. Nevertheless, the evidence to date suggests that changes to the endogenous and exogenous components during both the development and decay of circadian rhythms are involved. This being the case, and accepting that poorly developed circadian rhythms are often associated with poor general health and development, methods to strengthen circadian rhythms are described.

The circadian system and the therapeutics of the affective disorders.

Establishing that a circadian rhythm is abnormal tells us little about the cause, which can arise from changes in the patient's lifestyle, irregularities of the body clock or a malfunction in the process of entrainment of the clock. In a clinical context, such a range of possible explanations implies differences in the most appropriate mode of treatment. Against this background, the conventional view that the underlying abnormality in endogenous depression is due to a disorder of the body clock is challenged. The challenge is based on difficulties of interpretation of the clinical data and the results of studies on circadian rhythms in patients. It is suggested that the state of the circadian system in depression resembles its state in healthy individuals after time-zone transitions or in shift work maladaptation syndrome and that this disturbance should be seen as resulting from changes in the phasing of external zeitgebers rather than from an abnormality in the clock itself.

The adjustment of the circadian rhythm of body temperature to simulated time-zone transitions: a comparison of the effect of using raw versus unmasked data.

Deep body temperature and sleep/activity diaries data were recorded during control days and for 6 days after simulated time zone transitions of 8 h to the east (six subjects) or west (seven subjects). Circadian rhythms were assessed by cosinor analysis of both raw data (the conventional method) and purified data (corrected for the effects of sleep and activity). Analysis of raw data gives misleading information about the phase and amplitude of the rhythms due to the masking effects of the exogenous component. Use of purified data indicates that during the process of adjustment after an eastward shift (a) phase changes are more erratic than after a shift to the west; (b) no marked decrease in the amplitude of the rhythms is evident; and (c) no clear evidence exists that the circadian rhythm breaks up temporarily. The masking effect was less after the time zone transition if sleep maintenance was poor.

Can insulated skin temperature act as a substitute for rectal temperature when studying circadian rhythms?

We measured rectal, lateral chest wall, and axillary temperature every half hour for at least 24 h while subjects were living normal life-styles and keeping a sleep/activity diary. We then used a purification method to estimate the decrease of temperature due to sleep and the increases due to sitting, standing, walking, or exercising, as well as the parameters of the cosine curve that described the "purified data." Cosinor analysis of raw and purified data showed that the acrophases from both skin sites were much more variable and up to 8 h later than were those from the rectum (particularly if exercise had been taken), even though the acrophases from the two skin sites were similar to each other. For rectal temperature, there was an increase in the size of the masking effect as activity progressed through the sequence: sitting, standing or walking, exercising. In contrast, for both chest wall and axillary temperatures, although sitting produced masking effects similar to those for rectal temperature, masking effects due to standing or walking and exercising were much smaller, and sometimes they were even less than the masking effects due to sitting. These results indicate that our measurements of cutaneous temperature did not act as a substitute for rectal temperature, particularly when the subject was physically active rather than sedentary.

The attitudes and general health of student nurses before and immediately after their first eight weeks of nightwork.

A group of 43 student nurses were studied before and immediately after their first eight weeks of nightwork. Volunteers answered questions about their general health, sleep, and eating habits, as well as their social lives and relationships with friends. In all measures there was a deterioration produced by nightwork. About half the subjects volunteered the view that the forthcoming nightwork would cause a decline in the standard of their lifestyle or that it would improve now that nightwork had finished. This subgroup showed a significantly greater deterioration in interpersonal relationships, even though general health status was not significantly different. These results indicate that the problems associated with nightwork can arise before coping mechanisms can be expected to have been devised, and even in anticipation of nightwork. They imply that counselling is needed before nightwork is actually started.

Masking and the evolution of circadian rhythmicity.

In spite of the clear-cut temporal features exhibited by most species, temporal characteristics have merited little attention from evolutionists. However, it is logical to assume that since the environment oscillates cyclically, organisms that adapt to it must also oscillate; that is, cyclic factors have a clear evolutionary role. This article discusses evidence that the timing system is genetically determined; the role of environmental cues such as zeitgebers and masking factors; the temporal basis of mating; and masking as a disorganizing factor.

The development of circadian rhythmicity in neonates.

Eleven healthy, full-term babies were studied on the second day (d2) after birth and again 4 weeks (w4) later. The babies lived in natural lighting conditions and were fed every 4 h. Blood pressure, heart rate, skin (abdomen) and rectal temperatures were measured at 10-min intervals for 24 h. Behavioural states (deep sleep, light sleep, drowsy, alert, crying) were measured at the same times, and used to purify the raw data. Both the raw and purified data were assessed for circadian (24-h) rhythmicity by cosinor analysis. Circadian rhythms in heart rate and blood pressure were poorly developed at d2 and w4. By contrast, skin and rectal temperatures showed circadian rhythmicity that increased in amplitude between d2 and w4; this increase was seen in both raw and purified data. The masking effect due to sleep changed also; the depression caused by "deep sleep" became greater between d2 and w4. The results indicate that the development of circadian rhythmicity in body temperature was not secondary to that of a circadian pattern of sleep and activity, and presumably derives from a body clock that is beginning to develop independently.

Deriving a "phase response curve" from adjustment to simulated time zone transitions.

Thirty-eight subjects in groups of two to four have been subjected to simulated time zone transitions of 8 hr eastward, 8 hr westward, or 12 hr; all experiments have taken place in a temporal isolation unit, in which the light intensity during the waking periods was 250-300 lux. Circadian rhythms of rectal temperature have been used as a marker of the process of adjustment, the data being analyzed before (raw) and after "purification." Conventional results have been obtained, but when the data have been treated appropriately, they have produced a relationship between shift of the sleep-activity cycle and shift of the temperature rhythms that shows many characteristics of a phase response curve. Even though the factor or factors causing such adjustment are unknown, the results confirm that changes of a consonant set of "weak" zeitgebers is sufficient for entrainment to a new time zone to occur.

Effect of bright light on tolerance to night work.

Fifteen young (mean age 23.4 years) female nurses engaged in a resuscitation unit and working on a fast rotating shift schedule comprising two consecutive night shifts were exposed to short periods (4 x 20 min) of bright light (2350 lx) during their night duty to test a possible positive effect on their tolerance to night work. Two nights with normal lighting (20-380 lx) and two nights with bright light were compared. The following positive effects of bright light upon psychophysical conditions and performance efficiency were noted: in particular, signs of better physical fitness; less tiredness and sleepiness; a more balanced sleep pattern; and higher performance efficiency (letter cancellation test). This result could not be attributed to shifts of the internal clock although the exact cause remains to be determined. In fact, hormonal excretion and body temperature did not show any effect from bright light. In addition melatonin excretion was not suppressed appreciably by the bright light used.

Shiftwork, helplessness and depression.

Forty-three student nurses undertaking shiftwork for the first time participated in a study which tracked their perceptions of altered neurovegetative function, perceived criticism from others, sense of purpose and control and psychosomatic complaints. It was found that this first ever episode of shiftwork produced marked changes in all of the above. These findings have implications for circadian rhythm hypotheses of depression as well as for the methodology of future studies on cognitive or psychosocial variables in depression.

Circadian rhythms and masking: an overview.

Masking, as is well known, enables an organism to act immediately and in an appropriate way to changes of the environment, integrating with internally produced rhythmicity. It now appears that masking can be used to cover a far wider range of problems than was originally intended. To separate masking effects from the effects due to an internal oscillator, several techniques have been used. Such protocols, however, like the constant routine protocol, often replace one form of masking by another. The situation becomes even more complex when one realizes that the output of an internal oscillator modifies the input. The question might be asked whether it is possible to study the properties of the internal oscillator in vivo at all. This article attempts to produce a framework for future discussions.