In human volunteers who have been continuously experiencing unsatisfactory sleep, effects of glycine ingestion (3 g) before bedtime on subjective sleep quality were investigated, and changes in polysomnography (PSG) during sleep were analyzed. Effects on daytime sleepiness and daytime cognitive function were also evaluated. Glycine improved subjective sleep quality and sleep efficacy (sleep time/in-bed time), and shortened PSG latency both to sleep onset and to slow wave sleep without changes in the sleep architecture. Glycine lessened daytime sleepiness and improved performance of memory recognition tasks. Thus, a bolus ingestion of glycine before bedtime seems to produce subjective and objective improvement of the sleep quality in a different way than traditional hypnotic drugs such as benzodiazepines.

To estimate the process of re-entrainment we measured the melatonin rhythm on an eastward flight. After the baseline study, 24-hour blood sampling of six male subjects was done on the first and fifth days. During the daytime the subjects were exposed to natural zeitgeber outdoors every day except the blood sampling day. They were analyzed with an illuminometer when under the bright light condition. Four of the six subjects showed orthodromic re-entrainment, another subject showed antidromic re-entrainment, and the other subject kept the baseline pattern of plasma melatonin. The rate of re-entrainment in orthodromic re-entrainment was about 55 min per day. Measuring the circadian rhythm of plasma melatonin has clarified the interindividual re-entrainment difference.

Fatigue reduces productivity and is a risk factor for lifestyle diseases and mental disorders. Everyone experiences physiological fatigue and recovers with rest. Pathological fatigue, however, greatly reduces quality of life and requires therapeutic interventions. It is therefore necessary to distinguish between the two but there has been no biomarker for this. We report on the measurement of salivary human herpesvirus (HHV-) 6 and HHV-7 as biomarkers for quantifying physiological fatigue. They increased with military training and work and rapidly decreased with rest. Our results suggested that macrophage activation and differentiation were necessary for virus reactivation. However, HHV-6 and HHV-7 did not increase in obstructive sleep apnea syndrome (OSAS), chronic fatigue syndrome (CFS) and major depressive disorder (MDD), which are thought to cause pathological fatigue. Thus, HHV-6 and HHV-7 would be useful biomarkers for distinguishing between physiological and pathological fatigue. Our findings suggest a fundamentally new approach to evaluating fatigue and preventing fatigue-related diseases.

The effects of glycine on sleep quality were examined in a randomized double-blinded cross-over trial. The volunteers, with complaints about the quality of their sleep, ingested either glycine (3 g) or placebo before bedtime, and their subjective feeling in the following morning was evaluated with the St. Mary's Hospital Sleep Questionnaire and Space-Aeromedicine Fatigue Checklist. The glycine ingestion significantly improved the following elements: "fatigue", "liveliness and peppiness", and "clear-headedness". These results suggest that glycine produced a good subjective feeling after awakening from sleep.

In order to assess the effect of melatonin on jet lag a field study was undertaken. The process of re-entrainment of circadian melatonin rhythm was investigated in six subjects. Except during 24-h blood sampling, the subjects were exposed to natural zeitgeber (time giver) outdoors and given 3 mg melatonin at 23:00 h. The subjects were exposed to bright sunlight from 3000 to 12 000 lx. All of them showed orthodromic re-entrainment with taking melatonin, while two out of the six did not show orthodromic re-entrainment without taking melatonin. Melatonin accelerated the rate of the re-entrainment of the circadian melatonin rhythm. Melatonin was useful to jet travel from Tokyo to Los Angeles.

The purpose of this study was to compare the efficacy of individual and group cognitive behavioral therapy for insomnia (CBT-I) in outpatients with primary insomnia diagnosed by DSM-IV-TR. The participants were 20 individually treated (I-CBT-I) and 25 treated in a group therapy format (three to five patients per group) (G-CBT-I), which showed no significant difference regarding demographic variables between groups. The same components of CBT-I stimulus control therapy, sleep restriction therapy, cognitive therapy, and sleep hygiene education were applied on both groups. The short-term outcome (4 weeks after treatment) was measured by sleep logs, actigraphy, the Pittsburgh Sleep Quality Index (PSQI), and the Dysfunctional Beliefs and Attitudes about Sleep Scale (DBAS), and was compared between I-CBT-I and G-CBT-I. The results indicated that CBT-I was effective in improving subjective and objective sleep parameters and subjective sleep evaluations for both individual and group treatment. However, I-CBT-I resulted in significantly better improvements over G-CBT-I, in (i) objective and subjective sleep onset latency time, (ii) objective sleep efficacy and moving time during sleeping, (iii) overall sleep quality and duration of actual sleep time in PSQI, (iv) consequences of insomnia, control and predictability of sleep, sleep requirement expectation, and sleep-promoting practices in DBAS. The present study suggested the superiority of I-CBT-I over G-CBT-I in clinical settings, and further evaluations are necessary.

Aim: Twenty patients (14 of them women) suffering from psychophysiological insomnia (PPI) were enrolled for cognitive behavior therapy (CBT). The mean age of the patients was 56.9 years, and the mean duration of insomnia morbidity was 8.9 years. Each received individual combined CBT treatments consisting of stimulus control, sleep reduction, cognitive therapy and sleep hygiene education over a period of 1 month.Methods: Just before the CBT and after its completion, sleep measurements were conducted that involved (i) sleep logs, Dysfunctional Beliefs and Attitudes about Sleep Scale (DBAS), and the Pittsburgh Sleep Quality Index (PSQI); (ii) actigraphy measurement; (iii) dissociation between subjective and objective evaluation of sleep calculated from sleep logs and actigraphy results; and (iv) correlation between DBAS and the aforementioned sleep parameters. Because the intention was to focus on patients' incorrect cognition about sleep, the definition 'changes in dissociation between the sleep log and actigraphically measured sleep' was used as the primary outcome and 'changes in DBAS score' as the secondary outcome.Results: After the CBT the following was found: (i) underestimation by PPI patients of the objective evaluation of sleep; (ii) a decrease in the dissociation between the subjective and objective evaluation of sleep; (iii) improvement of the DBAS; and (iv) improvement of sleep logs and actigraphy measurements. Moreover, there was a correlation between the improvement of PSQI, sleep logs and DBAS.Conclusion: CBT for insomnia is able to redress incorrect cognition about sleep, leading to improvement of the disorder.

We investigated the re-entrainment of melatonin rhythm in an 11-h eastward-bound flight. Eight male subjects participated in the present study. Blood sampling was carried out once before the flight and twice after the flight. During the daytime the subjects were exposed to natural zeitgeber outdoors on the day except the blood sampling. Seven of eight subjects showed antidromic re-entrainment, and the other subject showed orthodromic re-entrainment. The intensity of natural day light in New York amounted to 20 000 lx. As for the direction of the re-entrainment in New York the antidromic re-entrainment is naturally dominant.