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Aim: The current study aimed to examine the effect of Japanese policies for appropriate hypnotics use and novel hypnotics (e.g. melatonin receptor agonist and orexin receptor antagonist [ORA]) on long‐term prescriptions of hypnotics. Methods: This retrospective study was conducted using a large‐scale health insurance claims database. Among subscribers prescribed hypnotics at least once between April 2005 and March 2021, those prescribed hypnotics for the first time after being included in the database in three periods (period 1: April 2012–March 2013; period 2: April 2016–March 2017; and period 3: April 2018–March 2019) were eligible. These were set considering the timing of the 2014 and 2018 medical fee revisions (2014 for polypharmacy of three or more hypnotics, 2018 for long‐term prescription of benzodiazepine receptor agonists for >12 months). The duration of consecutive prescriptions of hypnotics over 12 months was evaluated. Factors associated with short‐term prescriptions of hypnotics were also investigated. Results: In total, 186 535 participants were newly prescribed hypnotics. The mean duration of prescriptions was 2.9 months, and 9.3% of participants were prescribed hypnotics for 12 months. Prescription periods were not associated with short‐term prescriptions of hypnotics. ORA use was associated with short‐term prescriptions of hypnotics (adjusted hazard ratio, 1.077 [95% confidence interval, 1.035–1.120]; P < 0.001), but melatonin receptor agonist use was not. Conclusion: Japanese policies had no statistically significant effect on long‐term prescriptions of hypnotics. Although this study suggests initiating ORA for insomniacs as a candidate strategy to prevent long‐term prescriptions of hypnotics, further research is necessary to draw conclusions. [ABSTRACT FROM AUTHOR]

To assess circadian preference with a score, the Morningness-Eveningness Questionnaire (MEQ) has been used for more than 3 decades now. More recently, the Munich ChronoType Questionnaire (MCTQ) was developed: it asks for sleep-wake behavior on work and free days and uses the midpoint of sleep on free days (MSF), corrected for sleep debt accumulated during the work week as an indicator of chronotype (MSFsc). In this study, we developed a Japanese version of the MCTQ by using a translation/back-translation approach including an examination of its semantic validity. In a subsequent questionnaire survey, 450 adult men and women completed the Japanese versions of the MCTQ and MEQ. Results showed that MEQ scores were significantly negatively correlated with mid-sleep parameters assessed by the MCTQ, on both, work and free days, as well as with the chronotype measure MSFsc ( r = −0.580 to −0.652, all p < 0.001). As in the original German version, the strongest correlation was observed between MEQ score and MSF. A physiological validation study using dim light melatonin onset as a circadian phase marker ( N = 37) showed a high correlation between chronotype as assessed with the MSFsc ( r = 0.542, p < 0.001), and less so for MEQ score ( r = −0.402, p = 0.055). These results demonstrate the validity of the Japanese MCTQ and provide further support of the adequacy of the MCTQ as a chronotype measure. [ABSTRACT FROM AUTHOR]

Background: Circadian rhythm sleep disorder, free-running type (FRT), is an intractable sleep disorder in which sleep and wake times progressively delay each day even in normal living environments. This disorder severely affects the social functioning of patients because of periodic nighttime insomnia, excessive daytime sleepiness, and a high rate of comorbid psychiatric disorders. Although abnormal regulation of the biological clock is suspected, the pathophysiology of FRT has yet to be elucidated. In this study, the endogenous circadian period, τ, of FRT patients with normal vision was compared with that of healthy individuals whose circadian rhythms are entrained to a 24-hour cycle. Methods: Six FRT patients and 17 healthy individuals (9 intermediate chronotypes and 8 evening chronotypes) were subjected to a 7-day, 28-hour sleep–wake schedule according to the forced desynchrony protocol. Phase shifts in melatonin rhythm were measured under constant routine conditions to calculate τ. Results: In FRT patients, τ was significantly longer than in intermediate chronotypes, whereas in evening chronotypes, it ranged widely and was not significantly different from that in FRT patients. Moreover, τ of melatonin rhythm in FRT patients showed no significant correlation with τ of sleep–wake cycles measured before the study. Conclusions: The findings suggest that although a prolongation of τ may be involved in the onset mechanism of FRT, a prolonged τ is not the only factor involved. It appears that several factors including abnormal entrainment of circadian rhythms are involved in the onset of FRT in a multilayered manner. [ABSTRACT FROM AUTHOR]

Abstract: Humans have the ability to estimate the passage of time in the absence of external time cues. In this study, we subjected 22 healthy males (aged 21.8±1.9 years) to a 40-min nap trial followed by 80min of wakefulness repeated over 28h, and investigated the relationship between various sleep parameters and the discrepancy (ΔST) of time estimation ability (TEA) during sleep, defined by the difference between actual sleep time (ST) and subjective sleep time (sub-ST) in each nap interval. Both ST and sub-ST were significant diurnal fluctuations with the peak in the early morning (9h after dim-light melatonin onset time, 2h after nadir time of core body temperature rhythm), and subjective sleep duration was estimated to be longer than actual times in all nap intervals (sub-ST>ST). There were significant diurnal fluctuations in discrepancy (sub-ST–ST) of TEA during sleep, and the degree of discrepancy correlated positively with increase in the amount of REM sleep and decrease in the amount of slow-wave sleep. These findings suggest that human TEA operates at a certain level of discrepancy during sleep, and that this discrepancy might be related to the biological clock and its associated sleep architecture. [ABSTRACT FROM AUTHOR]

Abstract: There are large inter-individual differences in pupil size and suppression of melatonin by exposure to light. It has been reported that melatonin suppression by exposure to light increases when pupils are pharmacologically dilated. However, the correlation between normal inter-individual difference in pupil size and melatonin suppression by exposure to light is not clear. Twenty-three healthy male subjects (22.6±2.7 years old) were exposed to light (1000lx) for 2h at night. The starting time of exposure to light was set to the ascending phase of melatonin concentration of each subject. Pupil area and saliva melatonin concentration were measured before exposure to light under dim light (15lx) and during exposure to light. There were large inter-individual differences in melatonin suppression and pupil area. The mean and standard deviation of percentage of melatonin suppression 2h after exposure to light was 57.2±22.1%. The mean and standard deviation of pupil areas before and 2h after exposure to light were 30.7±7.9mm2 and 15.9±4.8mm2, respectively. The percentage of melatonin suppression by light was positively correlated with pupil area during light exposure (r =0.525, p <0.02). Interestingly, it was also correlated with pupil area measured before exposure to light, under dim light (15lx) (r =0.658, p <0.001). These results suggest that inter-individual difference in pupil area positively correlates with melatonin suppression by light and that pupil area under dim light is a predictor of inter-individual differences in melatonin suppression by light. [Copyright &y& Elsevier]