Biological Rhythms and Sleep Disorders in Man: The Delayed Sleep Phase Syndrome

Abstract The delayed sleep phase syndrome is a form of insomnia with inability to fall asleep at conventional times but with normal sleep at a delayed clock time in respect of light-dark cycles, social, economic and family demands. The syndrome is the most common intrinsic disorder of human sleep-wake rhythmicity with a reported population prevalence rate of between 0.1 and 0.4%. In some clinics it accounts for 2-5% of all subjects with a primary complaint of evening insomnia. The syndrome is familiar in about one quarter of all subjects, more common in males than females and usually present around puberty. It needs to be distinguished from motivated sleep-phase delay associated with psychiatric problems, psychological factors or school avoidance behavior in adolescence. The delayed sleep phase syndrome is life-long and may involve several biological rhythms coupled to the sleep-wake cycle including core temperature, alertness and melatonin rhythms. The plasma melatonin pulse duration and amplitude is normal, with a slight delay in low-light melatonin onset as compared with subjects with a normal sleep-wake schedule in a similar environment. Light suppression (moderate intensity: 600 lux at 00.01–00.30) of melatonin secretion is of normal amplitude. Melatonin 5 mg po will advance sleep-phase but the response is not maintained on stopping treatment and depends on the exact timing of melatonin administration in relation to the endogenous melatonin cycle. The phase-response curves of sleep-wake cycles, body temperature and salivary melatonin profile after oral melatonin are described. Treatment strategies include the use of chronotherapy with a round-the-clock successive 2 hour delay in scheduled sleep onset time, phototherapy (10,000 lux for 30 minutes at 08.00 for 14 days), and melatonin 5 mg po at 22.00. Also, vitamin B12 treatment has been reported effective in some but not all subjects. The cause of the delayed sleep phase syndrome is uncertain, but both genetic and environmental factors are involved. There is no evidence of intra-uterine or perinatal involvement and the reported incidence of breast feeding is normal. Childhood development is also normal. Both paternal and maternal inheritance have been reported. One mechanism, as shown by the occasional progressive delay in sleep phase may involve the near 25-hour period of the endogenous pacemaker. Also, there may be a failure of normal entrainment mechanisms in the advance phase of the sleep-wake cycle.