We studied the relationship between the phase and the amplitude of the circadian temperature rhythm using questionnaires that measure individual differences in personality variables, variables that relate to circadian rhythms, age and sex. The ambulatory core body temperature of 101 young men and 71 young women was recorded continuously over 6 days. The temperature minimum (Tmin) and amplitude (Tamp) were derived by fitting a complex cosine curve to each day’s data for each subject. Participants completed the Horne–Ostberg Morningness–Eveningness Questionnaire (MEQ), the Circadian Type Inventory (CTI) and the MMPI‐2, scored for the Psychopathology‐5 (PSY‐5) personality variables. We found that the average Tmin occurred at 03.50 h for morning‐types (M‐types), 05.02 h for the neither‐types and 06.01 h for evening‐types (E‐types). Figures were presented that could provide an estimate of Tmin given an individual’s morningness–eveningness score or weekend wake time. The Tmin occurred at approximately the middle of the 8‐h sleep period, but it occurred closer to wake in subjects with later Tmin values and increasing eveningness. In other words, E‐types slept on an earlier part of their temperature cycle than M‐types. This difference in the phase‐relationship between temperature and sleep may explain why E‐types are more alert at bedtime and sleepier after waking than M‐types. The Tmin occurred about a half‐hour later for men than women. Another interesting finding included an association between circadian rhythm temperature phase and amplitude, in that subjects with more delayed phases had larger amplitudes. The greater amplitude was due to lower nocturnal temperature.

We investigated the impact of light exposure history on light sensitivity in humans, as assessed by the magnitude of the suppression of melatonin secretion by nocturnal light. The hypothesis was that following a week of increased daytime bright-light exposure, subjects would become less sensitive to light, and that after a week of restriction to dimmer light they would become more sensitive. During the bright week, subjects (n = 12) obtained 4.3 ± 0.4 hr of bright light per day (by going outside and using light boxes indoors). During the dim week, they wore dark goggles (about 2% light transmission) when outside during daylight and spent 1.4 ± 0.9 hr per day outside. Saliva samples were obtained every 30 min for 7 hr in dim light (<15 lux) on two consecutive nights (baseline and test night) at the end of each week. On the test night, 500 lux was presented for 3 hr in the middle of the collection period to suppress melatonin. There was significantly more suppression after the dim week compared with after the bright week (to 53 versus 41% of the baseline night values, P < 0.05). However, there were large individual differences, and the difference between the bright and dim weeks was most pronounced in seven of the 12 subjects. Possible reasons for these individual differences are discussed, including the possibility that 1 wk was not long enough to change light sensitivity in some subjects. In conclusion, this study suggests that the circadian system's sensitivity to light can be affected by a recent change in light history.

Bright light therapy had a specific antidepressant effect beyond its placebo effect, but it took at least 3 weeks for a significant effect to develop. The benefit of light over placebo was in producing more of the full remissions.

Various combinations of interventions were used to phase-delay circadian rhythms to correct their misalignment with night work and day sleep. Young participants (median age = 22, n = 67) participated in 5 consecutive simulated night shifts (2300 to 0700) and then slept at home (0830 to 1530) in darkened bedrooms. Participants wore sunglasses with normal or dark lenses (transmission 15% or 2%) when outside during the day. Participants took placebo or melatonin (1.8 mg sustained release) before daytime sleep. During the night shifts, participants were exposed to a moving (delaying) pattern of intermittent bright light (approximately 5000 lux, 20 min on, 40 min off, 4-5 light pulses/night) or remained in dim light (approximately 150 lux). There were 6 intervention groups ranging from the least complex (normal sunglasses) to the most complex (dark sunglasses + bright light + melatonin). The dim light melatonin onset (DLMO) was assessed before and after the night shifts (baseline and final), and 7 h was added to estimate the temperature minimum (Tmin). Participants were categorized by their amount of reentrainment based on their final Tmin: not re-entrained (Tmin before the daytime dark/sleep period), partially re-entrained (Tmin during the first half of dark/sleep), or completely re-entrained (Tmin during the second half of dark/ sleep). The sample was split into earlier participants (baseline Tmin < or = 0700, sunlight during the commute home fell after the Tmin) and later participants (baseline Tmin > 0700). The later participants were completely re-entrained regardless of intervention group, whereas the degree of re-entrainment for the earlier participants depended on the interventions. With bright light during the night shift, almost all of the earlier participants achieved complete re-entrainment, and the phase delay shift was so large that darker sunglasses and melatonin could not increase its magnitude. With only room light during the night shift, darker sunglasses helped earlier participants phase-delay more than normal sunglasses, but melatonin did not increase the phase delay. The authors recommend the combination of intermittent bright light during the night shift, sunglasses (as dark as possible) during the commute home, and a regular, early daytime dark/sleep period if the goal is complete circadian adaptation to night-shift work.

The optimal administration time for advances and delays is later for the lower dose of melatonin. When each dose of melatonin is given at its optimal time, both yield similarly sized advances and delays.

Exogenous melatonin is increasingly used for its phase shifting and soporific effects. We generated a three pulse phase response curve (PRC) to exogenous melatonin (3 mg) by administering it to free-running subjects. Young healthy subjects (n = 27) participated in two 5 day laboratory sessions, each preceded by at least a week of habitual, but fixed sleep. Each 5 day laboratory session started and ended with a phase assessment to measure the circadian rhythm of endogenous melatonin in dim light using 30 min saliva samples. In between were three days in an ultradian dim light (< 150 lux)-dark cycle (LD 2.5 : 1.5) during which each subject took one pill per day at the same clock time (3 mg melatonin or placebo, double blind, counterbalanced). Each individual's phase shift to exogenous melatonin was corrected by subtracting their phase shift to placebo (a free-run). The resulting PRC has a phase advance portion peaking about 5 h before the dim light melatonin onset, in the afternoon. The phase delay portion peaks about 11 h after the dim light melatonin onset, shortly after the usual time of morning awakening. A dead zone of minimal phase shifts occurred around the first half of habitual sleep. The fitted maximum advance and delay shifts were 1.8 h and 1.3 h, respectively. This new PRC will aid in determining the optimal time to administer exogenous melatonin to achieve desired phase shifts and demonstrates that using exogenous melatonin as a sleep aid at night has minimal phase shifting effects.

SUMMAR Y The time at which the dim light melatonin onset (DLMO) occurs can be used to ensure the correct timing of light and/or melatonin administration in order to produce desired circadian phase shifts. Sometimes however, measuring the DLMO is not feasible. Here we determined if the DLMO was best estimated from fixed sleep times (based on habitual sleep times) or free (ad libitum) sleep times. Young healthy sleepers on fixed (n ¼ 60) or free (n ¼ 60) sleep schedules slept at home for 6 days. Sleep times were recorded with sleep logs verified with wrist actigraphy. Half-hourly saliva samples were then collected during a dim light phase assessment and were later assayed to determine the DLMO. We found that the DLMO was more highly correlated with sleep times in the free sleepers than in the fixed sleepers (DLMO versus wake time, r ¼ 0.70 and r ¼ 0.44, both P < 0.05). The regression equation between wake time and the DLMO in the free sleepers predicted the DLMO in an independent sample of free sleepers (n ¼ 23) to within 1.5 h of the actual DLMO in 96% of cases. These results indicate that the DLMO can be readily estimated in people whose sleep times are minimally affected by work, class and family commitments. Further work is necessary to determine if the DLMO can be accurately estimated in people with greater work and family responsibilities that affect their sleep times, perhaps by using weekend wake times, and if this method will apply to the elderly and patients with circadian rhythm disorders.k e y w o r d s bedtime, circadian rhythms, dim light melatonin onset, melatonin, sleep, wake

Afternoon melatonin, morning intermittent bright light, and a gradually advancing sleep schedule advanced circadian rhythms almost 1 h/d and thus produced very little circadian misalignment. This treatment could be used in any situation in which people need to phase advance their circadian clock, such as before eastward jet travel or for delayed sleep phase syndrome.