Tags: Circadian rhythm, DSPS, Non-24, Sleep research, Suprachiasmatic nuclei
The online N24 community has decided to name November 24 as N24 Awareness Day. We are encouraging bloggers and tweeters and anyone else with a platform to help spread awareness and knowledge of Non-24-Hour Sleep-Wake Disorder (N24).
The web page which links to these efforts is here (click on the N24 Day Logo):
One important advance was a paper by Kitamura et al. which measured the intrinsic circadian period in 6 patients with N24. They compared it with two groups of individuals without a circadian disorder. One group had an intermediate circadian preference. The other group had an evening preference. The latter group however did not have DSPS, only a preference for being active later in the day.
Kitmura et al. found that the intrinsic period of the N24s was 24.5 hours, which was significantly longer than that of the intermediate types, but not significantly longer than that of the evening types. The average period of the N24s was longer than that of the evening types but because of the great degree of overlap between those groups the difference was not significant. The longest period found in an evening type subject was nearly identical to the longest period among the N24 subjects (around 24.7 hours).
These results suggest that a longer-than-average intrinsic period is a component of N24, but it is not the only causative factor. Other factors, such as differences in phase angle between sleep and temperature rhythms, as found in several studies, may play a role.
Another paper, by An et al. did not discuss N24 explicitly, but the results may have import for those with the condition. They studied the effect of Vasoactive Intestinal Peptide (VIP) on shifting of circadian rhythms in mice and in cell cultures from the SCN. They found that VIP depending on time and dose could either enhance or reduce the mutual synchronization of SCN cells. Further, when SCN cells were less tightly synchronized together, they adapted more quickly to phase changes. This suggests that by manipulation of VIP levels it may be possible to increase the adaptability of the SCN to phase changes. Since N24s with a longer period need to change phase every day if they are trying to maintain a normal schedule, this approach might be of help. It might also help people with DSPS when trying to shift to an earlier sleep phase.
–posted by LivingwithN24
Kitamura S, Hida A, Enomoto M, Watanabe M, Katayose Y, Nozaki K, Aritake S, Higuchi S, Moriguchi Y, Kamei Y, Mishima K. Intrinsic circadian period of sighted patients with circadian rhythm sleep disorder, free-running type.Biol Psychiatry. 2013 Jan 1;73(1):63-9.
An S, Harang R, Meeker K, Granados-Fuentes D, Tsai CA, Mazuski C, Kim J, Doyle FJ 3rd, Petzold LR, Herzog ED. A neuropeptide speeds circadian entrainment by reducing intercellular synchrony. Proc Natl Acad Sci U S A. 2013 Nov 12;110(46):E4355-61.
Tags: Blogathon, Diagnosis, Disability, DSPS, narcolepsy
Julie Flygare, the author of Wide Awake and Dreaming: A Memoir of Narcolepsy, is hosting «Dear Diagnosis», a blogathon where she invites «all narcolepsy and chronic disease bloggers to write a letter to yourself on your diagnosis day.” To date, all responses are from narcolepsy bloggers. She needs one from another chronic disease blogger, I think.
Dear me in April 2004,
Elation! Finally a doctor who recognizes that you are not (just) lazy and inconsiderate. He understands so well that he asks about things you never realized were connected to your sleep problems. He asserts that you have a valid condition and even has a name for it: Delayed Sleep Phase Syndrome, which in years to come will be “uprated” to Delayed Sleep Phase Disorder.
Yes, you are on a high which will last several months, in spite of the fact that the treatment he recommends doesn’t really work. Thanking the heavens for the Internett, you will research DSPS and discover that its been known (but only to chronobiologists, apparently) for over 20 years. You will fill a couple of ring binders with scientific studies, learning to read and understand them along the way.
That overnight sleep study at the hospital in the early ‘90s that came up with “not narcolepsy” as a diagnosis should have rung a bell for that neurologist! Curses on him.
It will, unfortunately, take years for you to stop blaming it all on your own lack of self-discipline and to (re)gain some self-esteem. You will still have to make sincere apologies when you are late for work and miss appointments.
You will foolishly refuse to accept 100% disability when it is offered, going along with your GP who feels you should at least keep working part-time for social reasons. So you’ll be 40% disabled for a while, then 60%. Retirement age comes as a great relief.
You will actually start a blog about DSPS, partly for yourself but also in hopes of helping anyone who stumbles upon it. You’ll hear from thankful people; it’s great to be appreciated! You’ll find a wonderful support group, “niteowl”, online where intelligent and helpful people help each other learn. You’ll find other fora where you can help people. You’ll eventually start a wiki, then be a part of starting a non-profit, Circadian Sleep Disorders Network, to provide support, inform and try to spread awareness.
Your sleep specialist (yes, the same one as today) will tell you: “Now you can hang out a sign and start taking patients.” He’s joking, of course, but it’s a nice compliment.
In sum, your life will continue to center in large part around your sleep problems, as it always has, but increasingly in a positive way!
Me in 2013
Next post: 67. ~coming soon~
Tags: Circadian rhythm, DSPS, Non-24, Sleep diary, Sleep disorder
Keeping a sleep log or a sleep chart is one of the keys to getting a proper diagnosis of a circadian sleep disorder. Oftentimes someone will describe their sleep patterns, but it’s not always clear from the description when exactly they sleep. For example, someone will say they “keep going to bed later and later.” Depending on what they mean, that could either describe Non-24 Hour Sleep-Wake Cycle Disorder (N24) or a gradually worsening case of Delayed Sleep Phase Syndrome (DSPS). But a quick look at a sleep chart will usually clear up the distinction.
My eponymous co-blogger Delayed2Sleep, who has, of course, DSPS, has posted several of her sleep logs. Today I am going to post some of my sleep charts. My name is LivingwithN24 and I have, you guessed it, N24.
One thing I should note to start is that I have always charted my sleep on a vertical chart, whereas D2S has used a horizontal layout, so you’ll need to rotate the charts to compare them. I have also “double-plotted” some of my sleep charts. That means each line on the chart encompasses 48 hours. That’s a standard method in sleep studies as it helps the patterns to stand out more clearly.
These charts show a textbook case of N24. The phrase “textbook case” is not a metaphor here; the medical journal articles about my case are commonly cited in reviews of circadian sleep disorders. So there is no doubt you are looking at a case of N24 sleep. One can see that the sleep chart of an N24 shows a characteristic diagonal pattern as the bedtime and waking time slides gradually later each day. Unlike the case of DSPS, the delay does not stabilize at a particular clock time. Someone with DSPS may for example end up going to bed always around 6am for an extended period. Someone with N24 who goes to bed at 6am on Monday will likely go to bed at 7am on Tuesday, 8am on Wednesday, 9am on Thursday etc. until they have gone all the way around the clock. The delay is not always by one hour — I just chose that for simplicity. In my case I tended to delay 1.5 hours per day, meaning my “day” was actually 25.5 hours.
One can see in this chart that there is some irregularity in the sleep times, and there may also be daytime naps. Both of these showed up a lot in January and February of that year. But there is a nonetheless a clear pattern to the sleep. In some months such as March, April and May it stands out especially clearly.
It might also be of interest to compare these charts to another type of chart. In circadian medicine a technique called actigraphy is used. The patient wears a device called an actimeter on their wrist which records movement. Since people tend to move about a lot more when awake than when asleep, actigraphy can be a way of confirming the sleep times of a patient with N24 or DSPS. Here is an actigraphic chart of my sleep from around the same time as the sleep logs. The difference is the black squiggles on the actigraphic chart show time awake, rather than asleep, but the same diagonal pattern is present.
Now those charts are from 1991. The readers of this blog are clever folks and have no doubt noticed it is now 2010. I did this for a reason. Most of the studies of N24 have looked the subjects at one point in their lives. Few, if any, have examined how the sleep patterns of N24 change over the course of many years. I have noticed a number of changes in my sleep between 1991 and today.
One thing I noticed is that it is much more difficult to control my N24 with lights, darkness and sleeping medications. In fact, over this summer it became impossible. So in September I stopped using the lightbox and the sleeping pills to see what my sleep would do on my own.
Here is a sleep chart I made for the last 5 weeks (Sept 18-Oct 25, 2010). Instead of making the chart by hand I used the SleepChart program from supermemo.com.
This is quite different from the 1991 charts. While there is still a recognizable diagonal drift of the sleep times, it is much more erratic. The times of sleep are much less regular. Also there is a marked tendency to show two or more periods of sleep instead of one for each circadian day.
In some ways this pattern of sleep is in between that of Non-24 Hour Sleep Wake Cycle Disorder and that of Sleep Wake Cycle Disorder – Irregular Type. In the irregular type of sleep disorder, the person sleeps at almost random times of day or night and for varying lengths of time. Usually there are several short periods of sleep scattered at various time around the clock.
My sleep has not become completely irregular, but it is getting there. This is, to put it mildly, not a good thing. N24, bad as it is, has a least a little predictability to it. I could never predict my sleep out several weeks as some very regular N24s could do. But I could at least predict it fairly well 5 or 6 days out. Now I can barely predict what it will do from one day to the next and the urge to sleep or be awake comes upon me at almost random times.
Usually irregular sleep patterns are associated with conditions involving brain damage (injuries, tumors) or deterioration (dementia). However I suspect that in cases of severe circadian disorder the circadian system may deteriorate over time, leading to an evolution towards an irregular sleep pattern. My co-blogger has remarked that her DSPS sleep has some irregular elements as well.
Instead of a static snapshot of sleep which classifies the disorders as DSPS, N24 or irregular, research needs to look at sleep disorders as dynamic, evolving conditions. If someone has say, heart disease, we understand it will manifest itself differently at age 20 and 40 and 60. The same may be the case with circadian disorders. I had some sleep abnormalities from birth, classic DSPS from age 15 to 27, and N24 from then on. Now I seem to be trending towards irregular sleep. My approach to coping with this condition will have to change as well, but how that will happen I don’t yet know.
–posted by LivingWithN24
Next post: 61. Questions and answers about Non-24
Tags: Body clock, Chronotherapy, Circadian rhythm, DSPS, Non-24, Treatment
Treatments for circadian sleep disorders fall into three general categories. The first combines phototherapy and scototherapy, that is treatment with light and dark. The second is pharmacotherapy, usually using melatonin or one of its drug analogs. The third treatment is what I will discuss today and is known as chronotherapy.
None of these forms of treatment is universally successful — or there would be little need for this blog. Chronotherapy was the first treatment found to be successful for some cases of DSPS and thus was a major advance in treatment . The researchers who discovered it should be commended. But many valuable medical treatments also carry inherent risks. In particular anyone planning chronotherapy needs to know that it poses a risk of converting DSPS into the even more severe disorder known as non-24 hour sleep wake cycle disorder (N24).
This risk was first reported in a letter to the New England Journal of Medicine in 1992 by Dan Oren and Thomas Wehr of the NIH . They described three patients who had long-standing DSPS and had attempted to treat it by means of chronotherapy. In each of those cases the result was a persisting case of N24.
I can vouch for the accuracy of the NEJM article for one of the cases described is actually mine. I had DSPS for over 15 years before attempting to treat it by chronotherapy. That was the start of my current condition of N24.
The reason I am posting about this at this time is that I have gotten emails from people in recent years who have tried chronotherapy and who had also ended up as N24. These people were startled to find out that this risk was known 18 years ago. They were not aware of this risk prior to starting chronotherapy. Since chronotherapy is widely recommended, but the risk it poses is not widely known, I thought the subject needed to be addressed.
Two questions arise. Why does chronotherapy cause N24 in some cases; and how often does it do so?
To address the “why” question, let’s first review the difference between DSPS and N24. Someone with DSPS is unable to sleep except at a very delayed hour compared to most people. For example someone who sleeps every day from 4am to noon and cannot advance their sleep to normal hours would have the diagnosis of DSPS.
N24 is somewhat different. The sleeping time of someone with N24 changes from day to day. If they start out falling asleep at 4am, the next day they might not fall asleep until 6am, the following day at 8am, then 10am and so on, until they go around the clock. They might have a 26 hour day, as in that example, or any other day length longer than 24 hours, hence the name non-24 hour sleep-wake cycle disorder.
Returning to DSPS, while someone with DSPS cannot advance their sleep — cannot start going to bed at 2am if they are used to going to bed at 4am — they often can delay their sleep if they try. Thus it was proposed that they could normalize their sleep by going to bed later and later until they rolled around the clock to a normal sleep time. If they started at 4am they would be told to go to sleep the next day at 7am, then 10am then 1pm and so on until they reached a normal bedtime.
Described this way, it’s easy to see that chronotherapy for DSPS consists of temporarily following a schedule like that of someone with N24.
This first phase of chronotherapy is supposed to be followed by a second stabilization phase once the desired sleep time is reached. In the stabilization phase the subject is supposed to rigidly stick to the new bedtime and wake time.
Sometimes this works. Chronotherapy has been successful in some individuals. But not always. The N24 state, once entered into, is not so easy to reverse. In some persons, it is irreversible and they find that chronotherapy, far from curing their circadian problem, has instead converted it to a new, more impairing form.
There are two reasons why the transition to N24 can be difficult to reverse.
The first reason has to do with the relative phase of sleep compared to the phase of the body’s circadian rhythm which determines the phase response curve to light. In many cases of DSPS the delay of the sleep cycle relative to the light PRC means that such “nite owls” are asleep during the time at which the body need to be exposed to light in order to advance the timing of the circadian rhythm. When doing chronotherapy one goes to bed even later relative to the PRC. This decreases light exposure during the phase advance portion of the PRC and increases the light exposure during the phase delay portion of the PRC, causing a progressive delay of the circadian rhythm. The circadian rhythm determines the rhythm of sleep propensity so that delays as well. This sets up a positive feedback effect which tends to perpetuate the N24 state once it has been started. To reverse N24 once this feedback loop is started is very difficult.
A second reason may relate to findings in studies of animals on non-24 hour schedules (produced by a non-24 hour zeitgeber such as lights that go on and off every 25 hours). It has been found that prolonged maintenance on such a schedule changes the apparent period of the circadian rhythm, so that even when released from the non-24 hour zeitgeber into an environment of constant light or dark they continue to show signs of their prior N24 schedule . This was the reason cited in the original NEJM article.
How large is the risk of inducing N24 after chronotherapy? The NEJM article mentions 3 patients, which seems small until one recalls that the original article on chronotherapy in 1981 only cited 5 successful cases . There have been other reports of successful chronotherapy since then, but usually with small numbers of patients. Published cases of chronotherapy leading to N24 have been fewer; but as I mentioned, I have heard personally from other people in whom this has happened. There has been no systematic attempt to determine the relative risk. But given the small numbers of reported chronotherapy successes, the even smaller numbers of conversion to N24 cannot be considered negligible.
It may be that this risk could be reduced by the additional use of light boxes and dark therapy during the stabilization phase of chronotherapy. But this is speculation. The authors of the NEJM article suggest a slow advance of DSPS using light therapy as preferable to chronotherapy.
Of course not all DSPS patients will respond to slow phase advance by light therapy. For those who don’t the possibility of chronotherapy is tempting.
I am not someone who likes to make blanket statements. I would not suggest that chronotherapy be abandoned entirely. It does work for some. Nor am I criticizing the researchers who invented chronotherapy. Since prior to that there were no treatments at all for DSPS it was an important advance, and one that may still have its uses. But what I would say is that anyone starting chronotherapy needs to know that there is a risk it could make their circadian disorder worse. It is a calculated risk, although one in which we have little data to make that calculation accurately.
Many web sites and even medical texts mention the use of chronotherapy. Very few mention the risk that it can induce N24. One would have thought that an article in the prestigious New England Journal of Medicine would have been enough to get the word out, but clearly this aspect needs to be more widely discussed, which is why I am posting this.
—Posted by LivingWithN24 aka “L“
1. Czeisler CA, Richardson GS, Coleman RM, Zimmerman JC, Moore-Ede MC, Dement WC, Weitzman ED. Chronotherapy: resetting the circadian clocks of patients with delayed sleep phase insomnia. Sleep. 1981;4(1):1-21.
2. Oren DA, Wehr TA. Hypernyctohemeral syndrome after chronotherapy for delayed sleep phase syndrome. N Engl J Med. 1992 Dec 10;327(24):1762.
3.Pittendrigh CS, Daan S. A functional analysis of circadian pacemakers in nocturnal rodents. 1. The stability and lability of spontaneous frequency. J Comp Physiol [AI 1976;106:223-52.
Tags: Body clock, Diagnosis, DSPS, Genetics, Guest blogger
The body clock
A new list member wrote that his wife doubts the validity of Delayed Sleep Phase Syndrome, believes that his diagnosing doctor is a quack and believes that forcing oneself up early – often enough – will solve the problem.
Breann, with her knowledge of biology, responded:
Hi __, nice to meet you
It might help if your wife had a basic understanding of genetics. I’m not trying to be flip, many people don’t; they’re lucky if they get some Mendel in high school, and unfortunately, his “one gene, one trait” discovery is not true for everything. (The last time I checked, there were at least ten genes thought to be involved in the sleep-wake cycle. Whew!)
In my experience, it has simply never occurred to most people that they wake up or go to sleep for any reason other than being tired or not being tired; i.e. they believe it is mostly a conscious choice. They are unaware that their body has many complex and delicate systems keeping track of the time of day, how long they’ve been awake, how much or little food they’ve consumed, and so forth. Sometimes just teaching people that these seemingly simply urges aren’t TRULY conscious choices for anybody is a great help in their understanding that some or all of these systems can “go haywire” due to using a different set of instructions (different forms of the genes that regulate the processes).
Something that really worked with my friends and family was for me to simply sit them down and ask them flat-out: “You have known me my whole life. Do I seem like the kind of person who is going to malinger for decades just to get out of doing things that you KNOW I enjoy doing? Think about this logically. Am I that kind of person? Do you think I’m faking when I’m upset about getting fired, or missing an important appointment? Either your judgement of me over the last 20 years is totally wrong, or I am insane and need a lot more help than a sleep doctor.”
That flipped a light switch for them, I think. It was still hard for them to accept, and still is in some cases, but it at least got them to consider the fact that if there isn’t something wrong with me physically, than that leaves me as someone who has deliberately, yet unconsciously, set out to ruin my own life. That makes no sense, if they take a minute to think about it, and not just have a knee-jerk reaction.
Hope this helps!
Next: xlix. 2009: sleep logs