Phase response curve
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Phase response curve (PRC) illustrates the relationship between the timing of administration of a sleep phase affecting drug or treatment, and the effect on the sleep phase (a/k/a sleep timing). It has a sigmoidal ('S') shape when plotted as relative circadian time vs. phase shift magnitude. The time at which the curve reaches the peak is known as the acrophase.
An image of the PRC for light is here.
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[edit] Light PRC
Light therapy, typically with a light box producing 10,000 lux at a prescribed distance, has its greatest effect about five hours after usual bedtime. Starting about two hours before bedtime, exposure to bright light will delay the circadian phase, causing later wake-up time and later sleep onset. The closer to the middle of the night (relative to the individual's normal sleep-wake schedule), the greater the effect on circadian phase. This continues until acrophase about five hours after usual bedtime, when the effect changes abruptly from phase delay to phase advance. Immediately after acrophase, bright light exposure has its greatest phase advancing effect, causing earlier wake-up and sleep onset. The effect diminishes until about two hours after usual wake-up time, when it reaches zero. During the period between two hours after usual wake-up time to two hours before usual bedtime, bright light exposure has little or no effect on circadian phase (the slight effects prior to and following the daytime acrophase generally cancelling each other out).
Because losing sleep to obtain bright light exposure is considered undesirable by most people, it is usually done just prior to bedtime (to achieve phase delay), or just after awakening (to achieve phase advance).
[edit] Melatonin PRC
The phase-response curve for melatonin is roughly twelve hours out of phase with the phase-response curve for light. At usual wake-up time, exogenous (externally-administered) melatonin has a slight phase-delaying effect. The amount of phase-delay increases until about eight hours after wake-up time, when acrophase occurs and the effect swings abruptly from strong phase delay to strong phase advance. The phase-advance effect diminishes as the day goes on until it reaches zero about bedtime. From usual bedtime until wake-up time, melatonin has no effect on circadian phase.
The human body produces its own (endogenous) melatonin starting about two hours before bedtime, provided the lighting is dim. This is known as dim-light melatonin onset (DLMO). This natural action stimulates the phase-advance portion of the PRC and helps keep the body on a regular sleep-wake schedule. It also helps prepare the body for sleep.
Administration of melatonin at any time may have a mild hypnotic (sleep-inducing) effect. The resultant effect on sleep phase is governed by the PRC.
N.B. All times are approximate and vary among individuals. In particular, there is no convenient way of determining the exact timing of acrophase. For this reason, administration of either light or melatonin should generally be avoided for at least an hour on either side of the expected time of acrophase. This provides a safety margin to avoid producing the opposite effect of what is desired should actual time of acrophase differ from what is expected.
[edit] References
Rosenthal NE, et al. Phase-shifting effects of bright morning light as treatment for delayed sleep phase syndrome. Sleep 1990;13: 354–361.
Lewy A, Sack R, Fredrickson R, et al: The use of bright light in the treatment of chronobiologic sleep and mood disorders: The phase-response curve. Psychopharmacol Bull 1983; 19:523-525.
Lewy AJ, Ahmed S, Latham JM, et al. Melatonin shifts human circadian rhythms according to a phase-response curve. Chronobiol Int. 1992;9:380-392.
