The neurohormone melatonin as a marker, medicament, and mediator

This chapter is an update of what was originally published several years ago (Vessely and Lewy, 2002). Melatonin is a hormone produced by the pineal gland during nighttime darkness under the control of the endogenous circadian pacemaker (ECP) in the suprachiasmatic nucleus of the hypothalamus. The ECP is entrained (synchronized) to the 24-h light/dark cycle. The endogenous melatonin profile can be used to assess the phase position (time) of the ECP, and both bright light exposure and exogenous melatonin can influence its phase. Totally blind people often have free-running circadian rhythms that are not entrained to the 24-h light/dark cycle. In these blind free-runners (BFRs), circadian phase drifts each day, causing recurrent insomnia; properly timed low-dose melatonin can entrain BFRs to the 24-h day. Sighted people can have circadianrhythm disturbances as well. Both light and melatonin can be used to delay or advance circadian rhythms that are out of phase due to jet travel, shift work, or advanced or delayed sleep phase syndromes. Another group of people with circadian rhythm disorders are those suffering from seasonal affective disorder (SAD), or winter depression. Most people with SAD have circadian rhythms that delay in the winter, causing them to develop depressed moods and vegetative symptoms; light therapy timed to cause phase advances can lead to clear improvement. Preliminary work suggests that low-dose melatonin therapy may also be beneficial in treating SAD. The function of endogenous melatonin in humans may be to entrain the third-trimester fetus and suckling newborn to the mother's sleep/wake cycle.