The circadian rhythms of sleep-wakefulness, rectal temperature, and plasma melatonin were measured in 10 healthy male subjects for five consecutive seasons. To minimize direct effects of seasonally changing environmental factors, the subjects stayed in a living facility for 4 days in each season, where ambient temperature, humidity, and social contacts were controlled, while the light intensity of the living room was substantially influenced by natural daylight. Seasonal variations were found in the timing of sleep, the mean body temperature, the phases of circadian temperature and melatonin rhythms, and the phase relation between sleep and the rectal temperature rhythm. The subjects went to bed earliest in summer, intermediate in spring and autumn, and latest in winter. A similar but more pronounced seasonality was observed in the wake-up time, which was earlier in summer than in winter. The acrophases of the rectal temperature and plasma melatonin rhythms, which were calculated by fitting a cosine curve, were located in an earlier time of day in summer than in winter. The phase-angle difference of the rectal temperature rhythm to sleep varied seasonally and was more positive in summer than in winter. These findings indicate that not only the external (to the local time) but also the internal (between circadian rhythms) phase relations of the human circadian rhythms depend on season.

No abstract

A population survey of seasonality in six representative cities in Japan was conducted using the Japanese version of the Seasonal Pattern Assessment Questionnaire (SPAQ). The questionnaires were given to 951 parents (male: female ratio 1:1 age range 34-59 years) of high-school students. Significant regional differences in seasonal variations of mood, length of sleep, and weight were observed; the proportion of individuals reporting high seasonality in the two northern cities was significantly higher than that in the other areas. These results provide evidence for a northern predominance in the prevalence of seasonal affective disorder in Japan.

Several articles have appeared over the last years devoted to mental side effects during zonisamide (ZNS) treatment. In this study, we were particularly interested in psychotic episodes. Seventy-four epileptic patients with a history of ZNS treatment were surveyed retrospectively over the period spanning 1 March 1984 to 30 June 1994. They were divided into two groups according to the presence or absence of psychotic episodes during ZNS treatment. We analysed various factors pertaining to psychotic episodes during ZNS treatment. Of the 74 patients 14 had psychotic episodes. We found that the incidence of psychotic episodes during ZNS treatment was several times higher than the previously reported prevalence of epileptic psychosis, and that the risk of psychotic episodes was higher in young patients. In 13 patients, psychotic episodes occurred within a few years of commencement of ZNS. In children, obsessive-compulsive symptoms appeared to be related to psychotic episodes. It is important to terminate ZNS as soon as possible if psychotic episodes develop and never restart, even if seizures become worse. It cannot definitely be proved that ZNS causes psychotic episodes, as information on mental side effects during ZNS monotherapy is scant, but it does appear likely that ZNS contributes to psychotic episodes during polytherapy.

The aim of this study was to evaluate the efficacy and safety of ramelteon 4, 8, 16 or 32 mg and placebo in Japanese patients with chronic insomnia using a randomized, double-blind, five-period crossover design. A total of 65 Japanese patients with chronic primary insomnia received ramelteon or placebo for two nights each in sleep laboratories. Changes in sleep parameters were assessed objectively by polysomnography and subjectively by postsleep questionnaires. Safety and tolerability was evaluated by assessment of the occurrence of adverse events, next-day residual effects and laboratory and ECG investigations. Ramelteon 8 and 32 mg significantly shortened the mean latency to persistent sleep in comparison with placebo, and there was a statistically significant trend for linear dose-response for this sleep parameter. Overall changes in sleep architecture were modest (<3% changes vs placebo), with increases in stage 1 and decreases in stage 3/4. Ramelteon was well tolerated, the most common adverse effect being somnolence, which was similar to placebo at doses up to 8 mg, but increased with higher doses. Next-day residual effects occurred no more frequently with ramelteon at any dose than with placebo. When compared with sleep latency data from a similarly-designed US study, there was no evidence of any ethnic differences in the efficacy of ramelteon between Japanese and US patients. Overall, ramelteon 8 mg showed the most favorable balance between sleep-promoting effects and tolerability. The unique efficacy profile of ramelteon, promoting sleep initiation without affecting other sleep parameters, may be due to its circadian shifting effect.