Irregular sleep-wake rhythm disorder

Melatonin (upper right inset) is produced in the pineal gland. The production and secretion of melatonin is mediated largely by postganglionic retinal nerve fibers that pass through the retinohypothalamic tract to the suprachiasmatic nucleus, through the superior cervical ganglion, and finally to the pineal gland. This neuronal system is activated by darkness and suppressed by light (left insets). The activation of alpha1 and beta1 adrenergic receptors in the pineal gland raises cyclic AMP and calcium concentrations and activates arylalkylamine N-acetyltransferase, initiating the synthesis and release of melatonin. The daily rhythm of melatonin secretion is controlled by the endogenous master pacemaker located in the SCN, whereas timing in the SCN is in turn regulated by melatonin. The lower right inset shows the temporal relationship between the activity of the suprachiasmatic nuclei and the secretion of melatonin within a period of 24 hours (not to scale). (Adapted 2006, with permission, from: Brzezinski A. Mechanisms of disease: melatonin in humans. New Engl J Med 1997;336:186-195. Copyright © 1997 Massachusetts Medical Society.)
This sleep log indicates the periods of sleep for a patient with irregular sleep-wake rhythm disorder. The log was collected over a 14-day period. (Courtesy of Dr. Bradley V Vaughn.)
The y-axis shows the direction and relative magnitude of the phase shift produced by the administration of light (blue line) and melatonin (red line) at various times that are shown on the x-axis. The two x-axes show the time of melatonin administration or bright light exposure in either clock time (upper x-axis) or circadian time of hours before or after the dim light melatonin onset (DLMO) (lower x-axis). The rectangle represents sleep period, the reversed triangle represents the core body temperature nadir, and the arrow represents the DLMO. The clock time axis shows the DLMO at about 9 PM, sleep from about 11 PM to 7 AM, and the core body temperature nadir at about 4 AM. These represent the typical times and phase relationships among these rhythms when the circadian clock is entrained to a 24-hour day. For individuals with earlier or later circadian rhythms, the time axis should be adjusted accordingly. The phase response curves show the phase shifts to light or melatonin administration, but in a particular situation the overall 24-hour light-dark pattern, which includes the dark time during sleep, is important in determining the direction and magnitude of the resulting phase shift. The magnitudes of the phase shifts in the light and melatonin phase response curve should not be directly compared to each other as the magnitude will depend on the “dose” used and the magnitude of the shift of sleep/dark. (Reproduced from: Burgess HJ, Sharkey KM, Eastman CI. Bright light, dark and melatonin can promote circadian adaptation in night shift workers. Sleep Med Rev 2002;6(5):407-20. With permission from Elsevier.)

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