SUMMARYThe purpose of the study was to induce in two different ways, a phase-angle difference between the circadian pacemaker and the imposed sleep-wake cycle in humans, we intended to: (i) shift the circadian pacemaker by exposure to bright light and keep the timing of the sleep-wake cycle fixed; and (ii) keep the timing of the circadian pacemaker fixed by a constant light-dark cycle and displace sleep. We monitored dim light melatonin onset (DLMO), core body temperature and sleep. DLMO was delayed significantly after 3 days of a 3-h delayed sleep-phase when compared with 3 days of sleep at a normal or 3-h advanced sleep-phase. The shifts in DLMO were not accompanied by shifts in body temperature, changes in waking-up time or by a change in the duration of the first rapid eye movement (REM) sleep episode. Three days of light exposure in the morning or evening resulted in shifts in DLMO of similar magnitude, but this was accompanied by shifts in the rhythm of body temperature, changes in waking-up time and in the duration of the first REM sleep episode. We conclude that the changes observed after light exposure reflect shifts in the circadian pacemaker. In contrast, we propose that the changes observed in DLMO after sleep displacement are not mediated by the circadian pacemaker. These results raise some doubts about the reliability of DLMO as a marker of circadian phase in cases of sleep disturbances. Finally, we initiate a search for changes in sleep that might be responsible for the unexpected effects on DLMO.
In a crossover design, 8 nonseasonal depressed subjects, selected on the presence of diurnal mood variations, and 8 sex and age-matched controls were exposed to dim light (< 10 lux) in the evening (18:00-21:00 h) and bright light (2500 lux) in the morning (ML, 6:00-9:00 h), to dim light in the morning and bright light in the evening (EL), or to dim light both in the evening and in the morning (DL) during 3 consecutive days in each of these conditions. There were no initial phase differences between depressed and healthy subjects in the timing of dim light melatonin onset, sleep termination, and body temperature. The phase shifts after EL and ML in both healthy and depressed subjects were as expected on the basis of a human phase response curve. On average, there was no therapeutic effect of the light exposure in the depressed patients. Two patients improved, but these effects do not seem to be related to shifts in the circadian system.
Unequivocal results demonstrating a causal relationship between a disturbance in circadian rhythms and depression have not yet been reported (reviews). However, acute mood changes, such as the antidepressive effect of sleep deprivation, diurnal variations of mood and their interrelationship, are commonly put forward as evidence of the importance of circadian dysregulations in affective disorders. The purpose of the present study is to obtain more insight in the mechanisms underlying these mood changes. The results will be discussed in the context of a recently postulated non-chronobiological explanation. Earlier studies have suggested that the relationship between diurnal variation of mood and the response to total sleep deprivation (TSD) is clear and unambiguous: improvement of mood during the day prior to TSD (a positive diurnal variation) is followed by a positive response (mood improvement) to TSD, while no improvement or deterioration of mood during the day prior to TSD (a negative diurnal variation) may result in no, or even a negative, TSD response (for references see Van den Hoofdakker). However, these conclusions were based on the results from cross-sectional studies, comparing single TSD effects across individuals. Comparison of sleep deprivation effects within individuals, however, revealed that the course of mood during the day prior to TSD is irrelevant for the TSD response. Accordingly, a favourable response to TSD appeared to be related to the patient's propensity to show diurnal mood variations per se, irrespective of their direction.
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