Why the dim light melatonin onset (DLMO) should be measured before treatment of patients with circadian rhythm sleep disorders.

Treatment of circadian rhythm sleep disorders (CRSD) may include light therapy, chronotherapy and melatonin. Exogenous melatonin is increasingly being used in patients with insomnia or CRSD. Although pharmacopoeias and the European food safety authority (EFSA) recommend administering melatonin 1-2 h before desired bedtime, several studies have shown that melatonin is not always effective if administered according to that recommendation. Crucial for optimal treatment of CRSD, melatonin and other treatments should be administered at a time related to individual circadian timing (typically assessed using the dim light melatonin onset (DLMO)). If not administered according to the individual patient's circadian timing, melatonin and other treatments may not only be ineffective, they may even result in contrary effects. Endogenous melatonin levels can be measured reliably in saliva collected at the patient's home. A clinically reliably DLMO can be calculated using a fixed threshold. Diary and polysomnographic sleep-onset time do not reliably predict DLMO or circadian timing in patients with CRSD. Knowing the patient's individual circadian timing by assessing DLMO can improve diagnosis and treatment of CRSD with melatonin as well as other therapies such as light or chronotherapy, and optimizing treatment timing will shorten the time required to achieve results.

Intrinsic circadian period of sighted patients with circadian rhythm sleep disorder, free-running type.

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.

Night shift performance is improved by a compromise circadian phase position: study 3. Circadian phase after 7 night shifts with an intervening weekend off.

STUDY OBJECTIVE: To produce a compromise circadian phase position for permanent night shift work in which the sleepiest circadian time is delayed out of the night work period and into the first half of the day sleep period. This is predicted to improve night shift alertness and performance while permitting adequate late night sleep on days off. DESIGN: Between-subjects. SETTING: Home and laboratory. PARTICIPANTS: 24 healthy subjects. INTERVENTIONS: Subjects underwent 3 simulated night shifts, 2 days off, and 4 more night shifts. Experimental subjects received five, 15 minute bright light pulses from light boxes during night shifts, wore dark sunglasses when outside, slept in dark bedrooms at scheduled times after night shifts and on days off, and received outdoor afternoon light exposure (the "light brake"). Control subjects remained in normal room light during night shifts, wore lighter sunglasses, and had unrestricted sleep and outdoor light exposure. MEASUREMENTS AND RESULTS: The final dim light melatonin onset (DLMO) of the experimental group was approximately approximately 04:30, close to our target compromise phase position, and significantly later than the control group at approximately 00:30. Experimental subjects performed better than controls, and slept for nearly all of the allotted time in bed. By the last night shift, they performed almost as well during the night as during daytime baseline. Controls demonstrated pronounced performance impairments late in the night shifts, and exhibited large individual differences in sleep duration. CONCLUSIONS: Relatively inexpensive and feasible interventions can produce adaptation to night shift work while still allowing adequate nighttime sleep on days off.

The roles of melatonin and light in the pathophysiology and treatment of circadian rhythm sleep disorders.

Normal circadian rhythms are synchronized to a regular 24 h environmental light-dark cycle, and the suprachiasmatic nucleus and the hormone melatonin have important roles in this process. Desynchronization of circadian rhythms, as occurs in chronobiological disorders, can produce severe disturbances in sleep patterns. According to the International Classification of Sleep Disorders, circadian rhythm sleep disorders (CRSDs) include delayed sleep phase syndrome, advanced sleep phase syndrome, non-24 h sleep-wake disorder, jet lag and shift-work sleep disorder. Disturbances in the circadian phase position of plasma melatonin levels have been documented in all of these disorders. There is compelling evidence to implicate endogenous melatonin as an important mediator in CRSD pathophysiology, although further research involving large numbers of patients will be required to clarify whether the disruption of melatonin secretion is a causal factor in CRSDs. In this Review, we focus on the use of exogenous melatonin and light therapy to treat the disturbed sleep-wake rhythms seen in CRSDs.

Chromotherapy in the regulation of neurohormonal balance in human brain--complementary application in modern psychiatric treatment.

Chromotherapy is based on the effect of colored light with different frequencies on human neurohormonal pathways, precisely on melatonin and serotonin pathways in brain. There is evidence that visible electromagnetic spectrum of light we see as colors can have impact on human health, Cicardian rhythm or biological clock is complex fundamental physiological and biological cycle in human organism. The biological clock in humans is located in the specialized group of brain cells called suprachiasmatic nucleus (SCN) within the anterior hypothalamus. The complex process of neurohormonal regulation of cicardian rhythm in humans is essential for synchronized interaction and coordination of internal body function with the environment. Given these facts it is clear that any shift in cicardian rhythm results in neurohormonal imbalance which consequently could lead to various psychiatric disorders affecting humans. Studies on sleep disorders, depression, seasonal affective disorder (SAD) and post-traumatic stress disorder (PTSD) suggested that symptoms, signs, and biologic markers associated to these psychiatric disorders are due to marked alterations in melatonin and serotonin levels. The main hypothesis of chromotherapy is that specific colors of the visible spectrum are activators or inhibitors of complex physiological, biological and biochemical processes in human brain such as synthesis of various neurohormons. According to all previous findings, our goal is future investigation of the effect and possible application of chromotherapy in the complementary psychiatric treatment in patients with diagnostic criteria which are clearly related to melatonin and serotonin disturbances.

[Delayed wakefulness-sleep rhythm syndrome and melatonin. Synthesis of existing studies]. / Syndrome de retard de phase du rythme veille-sommeil et mélatonine. Synthèse des études existantes.

Delayed sleep phase syndrome involves undesirable late bed times and arising times with extreme difficulties in falling asleep and in awakening at a desired clock time. These patients present a delayed circadian system. Chronotherapy and phototherapy are designed to have a training effect on the circadian system. Response to these treatments varies widely and depends on the patient's motivation and associated psychological disorders. Other treatments have been proposed with less evident results. The few studies testing the effect of melatonin in delayed sleep phase syndrome concern a small number of patients and present methodological drawbacks. It can be concluded from these studies however that exogenous melatonin influences endogenous secretion more than other secretion rhythms. The effect on sleep time is significant but clinically moderate. More studies are needed to examine the effect of exogenous melatonin as a treatment strategy in delayed sleep phase syndrome.

Case of a mentally retarded child with non-24 hour sleep-wake syndrome caused by deficiency of melatonin secretion.

A case of a 5-year-old boy with non-24 hour sleep-wake syndrome and mental retardation is reported. His free-running sleep-wake rhythm was remarkably improved by the oral administration of melatonin. The circadian variation in melatonin secretion was extremely low, and circadian rhythm of cortisol secretion was noted. It was speculated that his non-24 hour sleep-wake syndrome was due to a congenital deficiency of melatonin secretion, and supplemental melatonin therapy proved effective for treating his condition.