SHED SOME LIGHT… on Non-24 Disorder

You may have seen commercials for a new drug, Hetlioz, airing on TV the last few weeks for a mysterious condition called Non-24 Circadian Rhythm Disorder (also known as Non-24, N24 or free running disorder). Non-24 is considered a circadian rhythm disorder which occurs in both blind people and people who are sighted. Those with Non-24 can struggle to keep to a regular schedule of work or classes. Those who are blind run a 40-70 percent risk of suffering from this disorder, which researchers still don’t understand fully, as it can equally effect people who have their sight.

Here are some good questions that help doctors to identify people struggling with Non-24 Disorder:

  • Do you struggle to fall asleep or stay asleep at night?
  • Do you find you are sometimes excessively sleepy at inappropriate times during the day?
  • Do you find it hard to concentrate on tasks?
  • Do you feel like you are never well rested even after sleeping?
  • Do you sleep at times that are remarkably different from those around you?
  • Do you feel as if you are the only one who has your sleep schedule?

It is important to see a doctor about these concerns as they point to multiple kinds of sleep disorders. And like many other sleep problems, Non-24 shares two major symptoms:

1. The inability to fall and/or stay asleep at night.
2. An overwhelming urge to sleep during the day.

These symptoms can point to the improper timing of hormone release in the body, primarily of two sleep-related hormones: melatonin (which encourages sleep) and cortisol (which encourages wakefulness and appetite). When these hormones run out of sync with one another they can impact the phasing which leads to normal sleep patterns. On top of that, sleep deprivation that comes as a result can lead to daytime cognitive dysfunction and mood disorders.

Those with Non-24 Disorder have brains which do not adequately time the release of the sleep-wake hormones melatonin and cortisol due to an abnormal circadian clock, which is found inside the brain (the suprachiasmatic nucleus, or SCN). As a result, their sleep-wake and other critical rhythms shift off schedule gradually every day, leading to significant disruptions in sleep-wake function until the circadian clock is eventually reset. 

Thanks to HetliozPro for use of this diagram.

Why do the hormones fall out of rhythm? Science isn’t sure. Most people have circadian rhythms that run around 24 hours; the cycles of sleep-wake and other drives rely on the regular timing of hormones in conjunction with external time cues (like light and dark) to keep these rhythms on track.

Somebody with Non-24 has a body clock which is set for longer or shorter than the 24 hour clock that most people function on, so they basically shift a little earlier or later each day in comparison to everyone else until their rhythms align outside of what is considered a normal schedule. Hence, they can become sleepy during the day due to a persistent shift in rhythms that forces their sleep drive to kick in at times which are incongruent with social norms.

For people who are sighted, Non-24 is fairly rare, but it may be amended by the use of light cues and phototherapy, matched with forced sleep schedules, to help inform the sleep drive mechanisms in the body. Managing light exposure is key to making melatonin work. However, those who are blind are less able (or unable) to use light exposure effectively to control melatonin production and need to try other methods to keep from “free running.”

How it Non-24 treated? Carefully timed phototherapy can help some people regain a regular rhythm or at least offset deep shifts so they can manage normal job or school schedules. A new melatonin receptor, Hetlioz (tasimelteon), was approved earlier this year by the FDA to treat Non-24 and can be obtained by prescription through specialty pharmacies.

For more information about Non-24, please visit these excellent websites.

Non-24 Hour Sleep-Wake Disorder || Facts & Prevalence || NSF
Circadian Sleep Disorders Network Non-24 Q&A

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3 Comments on SHED SOME LIGHT… on Non-24 Disorder

  1. Hi Kasha

    Here is my second, separate comment. I appreciate your bearing with me! And thank you again for sharing your story and for the links at the bottom of your comment.

    The goal at SHC is to make information about sleep health easy to access for the average person, who is often more inspired by and can learn more effectively from these personal stories (when compared to research studies, which are often written in medicalese or locked up in research databases they do not subscribe to).

    I appreciate that you may have felt I oversimplified Non-24, but I think our goals are actually the same here, and I think we both achieve the same message.

    As for confusing Non-24 with Day-Night Sleep Inversion, I think you may have misunderstood what I wrote, as I have not, in any way, described Non-24 as a complete and permanent flip flop of the sleep-wake cycle. Besides, according to my copy of the ICSD, Day-Night Sleep Inversion is a condition related to mental health disorders and not circadian rhythm dysfunction, therefore not even on my radar.

    As for clarifying how Non-24 works, I do believe I described daily shifting that falls out of sync with normal rhythms and not a permanent flip-flop of sleep-wake periods. From my post:

    “Somebody with Non-24 has a body clock which is set for longer or shorter than the 24 hour clock that most people function on, so they basically shift a little earlier or later each day in comparison to everyone else until their rhythms no longer align with what is considered normal. Hence, they can become sleepy during the day due to a persistent shift in rhythms that forces their sleep drive to kick in at times which are incongruent with social norms.”

    Perhaps you felt this implied that they had the same schedule all the time. Actually, as you know, their sleep-wake cycles are a moving target, sequentially shifting off schedule. Someone with Non-24 could have a clock set to less than 23 hours or more than 27 hours; since this does not align with the typical 24-hour day, there will always be desynchronization between their rhythms and the earth's rhythms.

    Yes, sometimes, they will need to sleep during the day because that is when their sleep cycle kicks in. And yes, they will also have days where they are awake because eventually their sleep cycle will kick in at a “socially appropriate time.” Again, their schedule is a moving target.

    The potential solutions I describe for treating Non-24 also originate from the aforementioned article published in SLEEP magazine as well as a brief reference to a new drug on the marketplace that works as a melatonin receptor.

    Thank you for offering more description about this condition from a personal perspective. I think it must be extremely difficult to live with Non-24 because our world is arranged into a particular order by the majority in society; those who have circadian disorders are challenged to fit inside this prevailing framework of time, but their bodies and brains are not going to be so easily altered.

    I encourage readers to consult the following study on Circadian Rhythm Disorders published by the AASM in 2007, but please note that it's not written for the general public but for health professionals, so you might find some of the language challenging:

    Circadian Rhythm Sleep Disorders: Part II, Advanced Sleep Phase Disorder, Delayed Sleep Phase Disorder, Free-Running Disorder, and Irregular Sleep-Wake Rhythm || http://www.aasmnet.org/resources/practiceparameters/review_circadianrhythm2.pdf

    Tamara

  2. You and interested readers may also want to see the Non-24 article at NORD, the National Organization for Rare Disorders. It's long, not full of medicalese but also not a particularly easy read:

    https://rarediseases.org/rare-diseases/non-24-hour-sleep-wake-disorder/

    And, by the way, Hetlioz (tasimelteon) is not a “melatonin receptor”, as those reside inside the body. It is one of several melatonin receptor agonists. The two earliest to come out were Rozerem (ramelteon, in the USA, 2005) and Valdoxan/Melitor/Thymanax (agomelatine, in Europe, 2009).

  3. You and interested readers may also want to see the Non-24 article at NORD, the National Organization for Rare Disorders. It's long, not full of medicalese but also not a particularly easy read:

    https://rarediseases.org/rare-diseases/non-24-hour-sleep-wake-disorder/

    And, by the way, Hetlioz (tasimelteon) is not a “melatonin receptor”, as those reside inside the body. It is one of several melatonin receptor agonists. The two earliest to come out were Rozerem (ramelteon, in the USA, 2005) and Valdoxan/Melitor/Thymanax (agomelatine, in Europe, 2009).

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  1. Best of Sleepyhead: See our best previous posts on the body clock – SleepyHead CENTRAL
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