Sleep

When Our Bodies Lose Track of the Time

Circadian rhythms can become desynchronized from external clock time.

Posted Dec 30, 2014

Circadian rhythms are patterns of biological activity that occur on a regular schedule throughout the course of the day. The term circadian means “about a day.”

These rhythms are extremely important for survival as they allow humans, plants, and animals to anticipate regular changes in the environment and biologically prepare for them. Although circadian patterns had been noted earlier, circadian rhythms were first demonstrated experimentally in plants in the 1700s. It was many years, however, before the underlying mechanisms of circadian processes were discovered.

The reason that these rhythms exist is that we live on a planet that has regular periods of light and dark. Being able to anticipate and automatically prepare for these periods can greatly improve the chances of survival of an organism. For example, nocturnal animals such as mice are quite vulnerable to predation when looking for food in the open during the brightly lit portion of the day. They have a much better chance of avoiding detection by predators when active in the dark of night. A system that allows a mouse to sleep during the day and become active as light levels fall has obvious advantages.

In the same way, Paleolithic humans were quite vulnerable during the night when color vision isn’t effective and it was dangerous to be out and about. Sleeping after dark and being alert during the brightly lit portion of the day worked to our ancestors’ advantage.

The hormone melatonin is important in the regulation of the circadian rhythm and signals the shift to either increased or decreased activity. As the “hormone of darkness,” the release of melatonin signals to the mouse that it is dark out and time to start looking for food, but in a human, the same hormone indicates that it is dark out and time to prepare for sleep.

In humans, the master clock that orchestrates the body’s 24-hour rhythm has been found to reside in the suprachiasmatic nuclei (SCN) that are located just above the optic chiasm. These two small bundles of cell bodies fire more frequently during the day than during the night. They also fire more during REM sleep and when people are awake than during deep sleep. The primary effect of the circadian clock is to promote wakefulness during the day and to support sleep consolidation during the night.

A major input to the SCN nuclei is light intensity information from the retina. These nuclei affect the pineal gland that is responsible for releasing melatonin, which signals darkness and the onset of drowsiness that leads to sleep. Melatonin levels are highest during the night and are suppressed during the day by bright light.

The cells in the SCN itself carry out the clock function through a complex self-regulated, genetically controlled, cyclic oscillating synthesis of proteins. This protein synthesis oscillates through positive and negative feedback loops so that levels of certain proteins rise in the morning, peak in the evening, and then decrease at night. Because of this process, the clock can function indefinitely without outside synchronization. If you live in a cave underground with steady light illumination throughout the day and night and have no artificial clocks to tell you what time it is, you will still wake during the (circadian) day and sleep during the (circadian) night.

But this day and night pattern will slowly shift over time. Research has shown that the human circadian rhythm is not exactly 24 hours in length. For most individuals, it is slightly more than 24 hours but can also be slightly less than 24 hours. Thus over time, the cave dweller will most likely slowly advance the sleep schedule and go to bed slightly later and get up slightly later each 24 hour period. In regular day-to-day life, the circadian rhythm is entrained or reset to external clock time by light, exercise, social activities, and so on. These are known as zeitgebers (time-giver in German) and are able to reset the clock so that it continually matches external social time relatively well. This lack of rigidity is helpful in coping with the changes in light duration that occurs with the changes in seasons.

When there's a lack of environmental cues to entrain the circadian rhythm, people and animals become “free-running,” the term used in chronobiology to designate the intrinsic circadian rhythm in the absence of external synchronization. When this condition occurs in humans outside of experimental conditions, it causes a circadian rhythm disorder known as the non-24 hour sleep-wake rhythm disorder (N24SWD).

In my practice, this is a relatively rare disorder to encounter as it primarily occurs in totally blind individuals. It can occur in other situations but is extremely rare unless there is total blindness that results in complete loss of ability to perceive light. It is estimated that over 50% of totally blind people have N24SWD and 50% to 80% of individuals with blindness report some sleep disturbance.

This condition results in both difficulty getting to sleep at night and difficulty staying awake during the day. There can be periods of increased difficulty with sleep and wakefulness as the free running circadian rhythm shifts over time. There are also periods of apparent remission as the free running circadian rhythm temporarily aligns with social clock time. This can make it very difficult for the individual to keep up with regular daily activities and engage in normal social interactions.

From a behavioral sleep medicine perspective, there are a number of strategies that have been employed to help patients with this disorder. Since the most powerful zeitgeber, light, is not an option for totally blind individuals, melatonin, the hormone of darkness, is used to help entrain the circadian rhythm. This is accomplished by regular administration of melatonin in the evening or at bedtime. Further entrainment may be accomplished through carefully scheduling a very regular bedtime, rise time, mealtime, and activity schedule.

Until recently, few pharmacological options existed for this disorder. Sleeping medication, as in other circadian rhythm disorders, has been used but is of limited benefit. A new melatonin agonist, tasimelteon, may offer some benefit over and above natural melatonin due to how it differentially affects the melatonin receptors.

While N24SWD is a dramatic and potentially debilitating circadian rhythm disorder, it does demonstrate both the power and importance of these rhythms for effective living. We live in an industrial civilization that is subtly and not so subtly creating the rhythm of our daily lives with artificial lighting and work schedules in ways that we are only beginning to understand. Circadian rhythms help our bodies prepare for regular changes in the environment such as the dark of night and the light of day. These rhythms are ubiquitous in nature and are found in both plants and animals. When cut off from cues to external time, as when a person is totally blind, these rhythms become desynchronized and can cause significant difficulty for living in society.

All circadian rhythm disorders, including the free running type, cause problems with both sleep and wakefulness and result in insomnia and excessive daytime drowsiness. N24SWD is a very difficult problem to treat, and recognition that it exists is the first step toward coping more effectively with it.

References

American Academy of Sleep Medicine (2014). International Classification of Sleep Disorders 3rd Edition. Darien, IL: American Academy of Sleep Medicine

Lee-Chiong, Jr., T. (2008). Sleep Medicine Essentials and Review. New York: Oxford University Press.