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SUMMAR Y The effect of artificial dawn during the last 30 min of sleep on subsequent dissipation of sleep inertia was investigated, including possible involvement of cortisol and thermoregulatory processes. Sixteen healthy subjects who reported difficulty with waking up participated in random order in a control and an artificial dawn night. Sleep inertia severity was measured by subjective ratings of sleepiness and activation, and by performance on an addition and a reaction time task measured at 1, 15, 30, 45, 60, and 90 min after waking up at habitual wake up time at workdays. At all intervals, saliva samples were collected for cortisol analysis. Sleep electroencephalogram was recorded during the 30 min prior to waking up; core body temperature and skin temperatures were recorded continuously until 90 min after waking up. Subjective sleepiness was significantly decreased and subjective activation increased after waking up in the artificial dawn condition as compared with control, in which lights were turned on at waking up. These effects can be explained by effects of artificial dawn on skin temperature and amount of wakefulness during the 30 min prior to the alarm. Artificial dawn accelerated the decline in skin temperature and in the distal-to-proximal skin temperature gradient after getting up. No significant effects of artificial dawn on performance, core body temperature, and cortisol were found. These results suggest that the physiology underlying the positive effects of artificial dawn on the dissipation of sleep inertia involves light sleep and an accelerated skin temperature decline after awakening.

Effects of artificial dawn on subjective ratings of sleep inertia and dim light melatonin onset Gimenez, Marina C.; Hessels, Martijn; van de Werken, Maan; de Vries, Bonnie; Beersma, Domien G. M.; Gordijn, Marijke C. M. Take-down policy If you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediately and investigate your claim.Downloaded from the University of Groningen/UMCG research database (Pure): http://www.rug.nl/research/portal. For technical reasons the number of authors shown on this cover page is limited to 10 maximum. The timing of work and social requirements has a negative impact on performance and well-being of a significant proportion of the population in our modern society due to a phenomenon known as social jetlag. During workdays, in the early morning, late chronotypes, in particular, suffer from a combination of a nonoptimal circadian phase and sleep deprivation. Sleep inertia, a transient period of lowered arousal after awakening, therefore, becomes more severe. In the present home study, the authors tested whether the use of an alarm clock with artificial dawn could reduce complaints of sleep inertia in people having difficulties in waking up early. The authors also examined whether these improvements were accompanied by a shift in the melatonin rhythm. Two studies were performed: Study 1: three conditions (0, 50, and 250 lux) and Study 2: two conditions (0 lux and self-selected dawn-light intensity). Each condition lasted 2 weeks. In both studies, the use of the artificial dawn resulted in a significant reduction of sleep inertia complaints. However, no significant shift in the onset of melatonin was observed after 2 weeks of using the artificial dawn of 250 lux or 50 lux compared to the control condition. A multilevel analysis revealed that only the presence of the artificial dawn, rather than shift in the dim light melatonin onset or timing of sleep offset, is related to the observed reduction of sleep inertia complaints. Mechanisms other than shift of circadian rhythms are needed to explain the positive results on sleep inertia of waking up with a dawn signal. (Author correspondence: m.c.gimenez@rug.nl)

Various lines of evidence suggest a mechanistic role for altered cAMP-CREB (cAMP response element - binding protein) signaling in depressive and affective disorders. However, the establishment and validation of human inter-individual differences in this and other major signaling pathways has proven difficult. Here, we describe a novel lentiviral methodology to investigate signaling variation over long periods of time directly in human primary fibroblasts. On a cellular level, this method showed surprisingly large inter-individual differences in three major signaling pathways in human subjects that nevertheless correlated with cellular measures of genome-wide transcription and drug toxicity. We next validated this method by establishing a likely role for cAMP-mediated signaling in a human neuroendocrine response to light - the light-dependent suppression of the circadian hormone melatonin - that shows wide inter-individual differences of unknown origin in vivo. Finally, we show an overall greater magnitude of cellular CREB signaling in individuals with bipolar disorder, suggesting a possible role for this signaling pathway in susceptibility to mental disease. Overall, our results suggest that genetic differences in major signaling pathways can be reliably detected with sensitive viral-based reporter profiling, and that these differences can be conserved across tissues and be predictive of physiology and disease susceptibility.

There is no difference between 1 and 2 weeks of LT in overall therapy outcome, but the speed of therapy response differed between 1 week LT and 2 weeks LT. Together with the significant correlation between expectations and therapy response in women, we hypothesize that expectations play a role in the speed of therapy response.

Human cortisol levels follow a clear circadian rhythm. We investigated the contribution of alternation of sleep and wakefulness and the circadian clock, using forced desynchrony. Cortisol levels were best described by a multiplication of a circadian and a wake-time component. The human cortisol response is modulated by circadian phase. Exposure to stress at an unnatural phase, as in shift work, is predicted to result in abnormal cortisol levels. Health of shift workers may therefore improve when stress is reduced at times when the clock produces high stress sensitivity.