When the day is too long, i.e. non-24-hour sleep-wake disorder

Published: 26-11-2022

A non-24-hour sleep-wake disorder (non-24), also known as a free-running rhythm, is one type of circadian rhythm sleep disorders (CRSD). People with this disorder live as if the day had not 24 hours, but, for example, 25 hours. If they can live in harmony with their rhythm, they go to sleep every day and wake up later than the day before, while trying to adjust to typical work or school hours is often fruitless for them.

What is circadian rhytm?

Many physiological processes occur in our bodies cyclically, in accordance with the circadian rhythm. The most obvious circadian rhythm is the sleep-wake cycle, but many other processes and parameters exhibit similar rhythms. During the day, changes for example body temperature, metabolism, heart rate, blood pressure, blood viscosity, production of certain hormones (cortisol, melatonin, prolactin, hormone growth).

Changes in the intensity of physiological processes make the symptoms of some diseases, e.g. rheumatoid arthritis, cardiac arrhythmias, epilepsy or gastric ulcer, change their intensity during the day. It was also noticed that the effectiveness and toxicity of some cancer drugs change rhythmically during the day.

Circadian rhythms are regulated by the biological clock (circadian clock). In humans, the central biological clock is located in the hypothalamus, specifically in the suprachiasmatic nuclei (SCN). Its task is to rhythmically turn on and off the transcription of special genes, the so-called clock genes, which makes individual processes occur cyclically with varying intensity. In addition to the central clock, in many organs (e.g. in the liver, adipose tissue, digestive tract) there are peripheral clocks. They control subordinate processes, such as digestion, and also influence the work of the central clock.

These cyclical processes are called “circadian” rhythms, not “day” rhythms, because the length of a cycle is usually not exactly 24 hours. Studies in which volunteers were placed for several weeks in rooms where they had no access to sunlight, watches, etc., showed that most people went into a rhythm that lasted a little more than 24 hours. Each day they fell asleep and woke up later, and after some time, without knowing it, they slept during the day and were active during the night. The exact length of the internal day in humans has not been established. Some studies have found it to be an average of 24.18 hours, others have found figures of 25 hours or something in between. It is certain, however, that in the vast majority of people the endogenous sleep-wake rhythm, as well as e.g. the rhythm of melatonin secretion and changes in body temperature run in cycles lasting a little longer than an earthly day.

However, we are able to live according to a 24-hour rhythm because the biological clock has the ability to shorten circadian rhythms to adapt to the environment. For this purpose, it collects information from the so-called zeitgebers (time givers). The main giver of time is light (or darkness), but other factors, such as eating meals and interactions with other people, also play a role.

Situations that desynchronize the biological clock, e.g. staying at night in a lighted room, changes in eating times caused by traveling to another continent or shift work often affect the functioning of the body and in some people may lead to, among others, insomnia, depression and metabolic disorders (e.g. type II diabetes).

Non-24-hour sleep-wake disorder (free-running sleep)

Unfortunately, not everyone is able to adapt their biological clock to a 24-hour cycle. People with a non-24-hour sleep-wake disorder, if they can, live as if the day lasted longer. However, it is not difficult to understand that due to obligations such as work, studies, family, few people have the opportunity to live this way. Therefore, people with this disorder in practice usually try to live according to a 24-hour cycle, but their other circadian cycles, such as the rhythm of changes in body temperature and secretion of hormones, run their own way. Therefore, during periods when circadian rhythms are properly aligned with the sleep-wake rhythm a person has to live with, they sleep well and show no symptoms of any sleep disturbance. In other periods, when the body indicates that it is time for sleep during the day, and at night it is time for activity for it, such people have difficulty falling asleep at night and feel sleepy during the day.

Free-running rhythm has a lot in common with another circadian rhythm disorder – delayed sleep phase syndrome. People with this disorder sleep at regular hours, but much later than normal hours, such as from 4 am to 12 am. Delayed sleep phase syndrome sometimes transforms into a free-running cycle. These disorders can also alternate.

Many people with a non-24-hour sleep-wake rhythm experience “jumps” in the cycle from time to time. Their circadian cycle is then shifted by 4 or more hours at a time (they fall asleep, for example, 5 hours later than the previous day). There is data showing that such people have a longer endogenous day than people with a free-running rhythm who do not make such “jumps” (about 26 hours compared to about 25 hours). In addition, people with non-24-hour sleep-wake disorder tend to sleep longer than healthy people (9-10 hours, not 7-8 hours).

In studies where participants were asked to stay awake for 24 hours, it was also noted that in people with a free-running rhythm, sleep deprivation does not accelerate the sleep phase. That is, healthy people, if they do not get enough sleep, will probably fall asleep earlier the next day. People with a non-24 disorder will have a problem with this (as will people with delayed sleep phase syndrome).

The non-24-hour sleep-wake disorder is very common in blind people who do not have the perception of light. Up to two thirds of such people struggle with it. It is a rare disorder in sighted people. However, it is relatively common in teenagers and people aged 20-30 (similar to delayed sleep phase syndrome and evening chronotype, which I wrote about in the article Teenage chronotype, or why lessons in schools should start at 11 am).

Causes of non-24-hour sleep-wake disorder

In the blind, the cause of the free-running rhythm is understandable. The most important time giver, which is light, is unavailable to their biological clock, which is why it has difficulty synchronizing with the environment.

In sighted people, the causes are not well understood and there may be several overlapping factors. Some people with a free-running rhythm have an endogenous day that is much longer than 24 hours, e.g. 26 hours, which exceeds the adaptive capacity of the biological clock. They may also be insensitive or too sensitive to light (despite normal vision) or have disorders in the production of melatonin.

It was also observed that, unlike healthy people who start to feel sleepy when their body temperature starts to drop, people with a free-running rhythm start feeling sleepy much later. Their bodies react similarly to melatonin. In healthy people, an increase in melatonin levels immediately causes drowsiness, while people with the non-24 disorder do not fall asleep until several hours after melatonin levels start to rise. Why this is happening is unknown.

Mutations in the genes that regulate circadian rhythms may be responsible for the free-running cycle. Unhealthy habits, such as staying up late in a brightly lit room, in front of a TV, computer or smartphone screen, can also be important. Strong light, and especially the blue component of light, emitted by screens delays the sleep phase in healthy people as well, and some people with a free-running sleep may be extremely sensitive to such stimuli.

Individual cases of people in whom a non-24-hour sleep-wake rhythm appeared after a brain injury or as a result of a brain tumor have also been described.

Treatment of non-24-hour sleep-wake disorder

In blind people, melatonin or drugs that activate melatonin receptors are used to treat the non-24-hour sleep-wake cycle. The drug registered specifically for the treatment of free-running rhythm (but only in blind people) is tasimelteon. Clinical studies have shown that after 1 month of therapy, the drug led to the synchronization of circadian rhythms in about 20% of patients, and after 7 months in almost 60%. In order to keep the biological clock in sync, it is necessary to take the drug constantly.

For sighted people, melatonin and light therapy (phototherapy) are used. The Polish Sleep Research Society and the Polish Psychiatric Association recommend that melatonin therapy should be started with a dose of 3-10 mg, which should be taken 1-2 hours before going to sleep. After 6-12 weeks, you should switch to lower doses (0.5-3 mg) to consolidate the sleep rhythm. It is best to start treatment when the sleep phase begins to move from the desired hours to later. In addition, they recommend the addition of phototherapy with light intensity of 2500 – 10000 lux. Depending on the intensity, the exposure should last 0.5 – 2 hours and should start immediately after waking up or – if possible – about 2 hours before waking up.

However, due to the small number of studies and small study groups, it is not possible to determine in what percentage of patients the therapy will be effective. Despite the lack of evidence from clinical trials, many experts believe that behavioral therapy should be added in addition. It consists in performing daily activities such as eating meals, socializing, exercising at certain, fixed times of the day. The hours of going to bed and waking up should also be constant, also on days off from work or school, and strong light, especially blue light, should be avoided in the evening.