OTHER FACTORS DETERMINING BIOLOGICAL CLOCK:

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The classic phase markers for measuring the timing of a mammal's circadian rhythm are:

·    melatonin secretion by the pineal gland

·      core body temperature


   ·      plasma level of cortisol.

For temperature studies, subjects must remain awake but calm and semi-reclined in near darkness while their rectal temperatures are taken continuously. The average human adult's temperature reaches its minimum at about 05:00 (5 a.m.), about two hours before habitual wake time, though variation is great among normal chronotypes.

Melatonin is absent from the system or undetectably low during daytime. Its onset in dim light, dim-light melatonin onset (DLMO), at about 21:00 (9 p.m.) can be measured in the blood or the saliva. Its major metabolite can also be measured in morning urine. Both DLMO and the midpoint (in time) of the presence of the hormone in the blood or saliva have been used as circadian markers. However, newer research indicates that the melatonin offset may be the more reliable marker. Benloucif et al. in Chicago in 2005 found that melatonin phase markers were more stable and more highly correlated with the timing of sleep than the core temperature minimum. They found that both sleep offset and melatonin offset were more strongly correlated with the various phase markers than sleep onset. In addition, the declining phase of the melatonin levels was more reliable and stable than the termination of melatonin synthesis.

One method used for measuring melatonin offset is to analyse a sequence of urine samples throughout the morning for the presence of the melatonin metabolite 6-sulphatoxymelatonin (aMT6s). Laberge et al. in Quebec in 1997 used this method in a study that confirmed the frequently found delayed circadian phase in healthy adolescents.[

A third marker of the human pacemaker is the timing of the maximum plasma cortisol level. Klerman et al. in 2002 compared cortisol and temperature data to eight different analysis methods of plasma melatonin data, and found that "methods using plasma melatonin data may be considered more reliable than methods using CBT or cortisol data as an indicator of circadian phase in humans.