Non-24 Hour Circadian Rhythm Sleep/Wake Cycle Disorder

[Marvin]

Hi Norway,

Yes you are right about night work and your sleep cycle. Shift work sleep disorder is a sleep disorder that affects people who frequently alternate shifts or work at night, contrary to the body’s natural circadian rhythms, and cannot adjust to their schedule.

Shift work intolerance, although listed as a circadian rhythm-related sleep disorder, should not be regarded as an inner biological clock issue or a sleep disorder alone. It can actually be a composite of three factors, which include, circadian, sleep, and domestic/social factors.

Marvin.

[Bright at Night]

Hello everyone who reads this thread

I'm sure you've heard it all before but I'm so excited about finding this site and just had to post something, somewhere. Mainly to offer thanks, show my appreciation for what your all doing here.

I don't know why, it seems strange now thinking about it, I'm 35 but I've never really looked into sleep disorders or tried to 'categorize' my sleep problems before. I guess I felt that it was just 'me' - how I am - if that makes any sense to anyone. Although that's not to say it hasn't been difficult from time to time.

But since my son was born I've been feeling a little stressed and guilty about sleeping at odd hours. He's two now and therefore keeping more normal hours has obvious benefits for everyone.

From the fact sheets here it seems I have some sort of DSPS and have possibly since I was an infant (my mother has informed me that she took me to a doctor because I did not sleep at night), though in fairness I don't recall the symptoms before my teenage years.

Anyway not to bore you all but this truly feels like a breakthrough discovery. The DSPS description on this site seems to fit me, (though I do seem to slide somewhat or hit a sweet 'normal-ish' rhythm for a few days sometimes. I usually feel the urge to sleep in the morning (around 10-11am at the moment) - night time I seem to switch on suddenly even if I've previously felt tired, feeling a compelling urge to 'do something' or be creative. The internet has been a massive crutch.

It's 7.14 am here atm and I've been up since 6pm-ish yesterday.

Thanks again!

P.S My wife was stunned by the description of DSPS, 'That's like you!' she said after reading the faq. She's always been 100% supportive. But from my point of view things seem more hopeful now- thanks!

[astroboy77]

hi guys,
its really comforting to read about other people with simllar symptons and painful stories from this horrible affliction.

people just dont really understand unless your living through this conditoin. my family are pretty tough on me and not very understanding, some of my friends too. but i really want to get 'cured'.

I like many others have a non 24hr Sleep wake pattern.I"m a 30yr old male. I tend to have about a 26hr day. And it continiously rolls over. sometimes i have couple normal waking days but not many in a row.

I've tried the usual things went to an overnight sleep study, where i was hooked up but nothing obvious came back. Also went to a few classes on sleep disorder/hygeine.

My question is where do i go from here? And how do you guys manage to book into and actually make an appt with a sleep speicalist? i've tried once before and missed it , ironicaly becuase i didnt wake up.

My GP's arent much help. I guess i have to try an expert sleep doctor again, maybe a different one this time Is it worht me trying light boxes and melatonin under my own supervision? Or shoudl this just be handled by expert guidance?

I've started to keep a sleep diary after reading about it on this forum. I'm sorry if my question has already been answered, if so just point me in the right direction woudl be much appreciated.

Thanks.

[Norway]

Hello Astroboy,

Do keep on keeping a sleep diary, as that will be the best aid both for yourself and for an expert if you someday find the right one. Not all "sleep doctors" know (much) about circadian rhythms, so you should shop for one who has treated DSPS and/or Non-24, preferably one with lots of experience with these disorders.

Getting "cured" may not be an option, but there are people, both blind and sighted, who have Non-24 under control with light and melatonin and expert guidance. Since there is more and more information available, it might be possible to self-treat if you are systematic and don't easily give up.

Here are the three "intro" sites I recommend; the last one is my own. They are about DSPS (delayed sleep-phase syndrome) but treatment is the same for that and for Non-24.
http://en.wikipedia.org/wiki/Delayed_sleep_phase_syndrome
http://dspsinfo.org/
http://delayed2sleep.wordpress.com
[Edit: corrected URL.]

[Hemmy]

Last night I learn about dsps . Well I think I have it . Weekly sleep deprivation - weekend sleep marathon. Alert at night - feel like Ive been shot with an elephant tranquiliser at 7 am when I get up for work. Getting phone calls after 10am on days off and weekends from friends and colleagues and pretending that I was up and about and putting on an "awake voice"(unconvincingly) . The people on the other end would say - "did i get you up ?" . Feeling guilty about sleeping past "normal" getting up times. thinking "does everybody feel this sleepy and lethargic in the morning when getting out of bed? Am I just a lazy loser?"
At high school people called me druggie cause I looked whacked out. At weekends I had to play football for my school in the morning - At the end of year dinner It was joked that I didnt wake up until the second half of the game - It was true . This has affected my life in a negative way but at least now I know its not my fault .

[Marvin]

Hey Norway!!!! Informative links about DSPS....thank you for sharing...

Marvi.

[Norway]

Gosh

[Marvin]

Hey Norway,

why gosh??

[black star]

Hi everyone. I think I have n-24, or at least a skewed version of DSPS. I guess I'm really adding a post because I've found reading all your posts very helpful, and there is such a dearth of information about this condition. It seems like having n-24 is as rare as leprosy or something, even though it seems quite natural to me to live like this. I'm 23 and have been like this since I was a teenager.

I don't seem to have quite as bad a problem as others here, but I do have tremendous difficulty waking up and forming any kind of routine. If I stay up an hour later, or stay in bed an hour later, that gets 'added on' to the next day; I find it very easy to progress in that direction and very hard to go in reverse. I am unemployed with depression, but I have a couple of voluntary jobs during the week.

Depending on how well I'm doing, I try to manage my wake-up time to be around 12-4pm, so I can do some things in the day and so when I have to be somewhere, I can do it, it's just hard. I can go later than this if I am not careful, and when I'm getting up later than 6pm, I do the 'trick' of staying up the whole night and braving the next day in zombie mode, in order to go to sleep at a time I think will mean I will start waking up at a more useful time. Example: this weekend, on Saturday I woke up about 6 pm, so I stayed up til Sunday 4 or 5pm and went to sleep until about 12pm Monday. Now I am back on track and hope to stay that way for a while

I think when I have something regular to do in the week, and I make sure I go to it every time (or as best as I can) then the problem is not as bad. I managed the first four months of this year without doing the stay-up-all-night trick. Most days were a struggle, though. I have less commitments now and so I am doing worse at managing it. Now I've read more about the condition, I'm ready to self-diagnose and self-treat as best I can, given the limited options. I'm looking at ordering a light box (any reccomendations?); I might order some Melatonin from the internet (type melatonin into google and it offers many ways to buy it in the uk) but I'm not convinced it's a good idea, perhaps just because it's not available here, possibly with good reason. As I understand it, light boxes help redress the melatonin balance anyway.

So, yeah, anyone reading this, feedback, questions, anything is welcome I'm just glad I've proof I'm not crazy/lazy/etc, although at the same time slightly put out that there is little information on what to do about it.

[Norway]

You can try melatonin, it's pretty harmless. I have DSPS and I've tried 3 mg, 1 mg and 0.5 mg. They all work for me, I find no difference. It's restricted (in Norway and UK at least) because there's no standard "recipe" or whatever they call it for medications. I have it on prescription, and my Norwegian pharmacy has had it from 3 different labs in the USA, all labeled "dietary supplement". The point is to get it from a reputable lab. I think one can only get the synthetic now (they decided making it from cows' brains might be a bad idea). Some people swear by the sub-lingual; I've never tried it.

Timing of both melatonin and light therapy is key; they should be about 12 hours apart, though there are individual differences. If you're Non-24, you should start treatment not just anytime, but when you're sleeping at a "normal" time. If you keep a sleep diary, it should help you see patterns and adjust, though an experienced expert sees the patterns better. I'm using the light at 8 a.m. and if I happen to wake up earlier, I wait until 8 to turn it on.

See the 3 websites I recommended in February on this thread. It is much easier to find info on DSPS than on Non-24, and the treatment is the same.

NB! I am not a doctor.

[serf]

Hi,
I don’t know where to start; my head is a maelstrom at the moment!

At the beginning of this year, 2007, I was diagnosed with an unknown Vitamin B12 metabolism problem. Although they couldn’t find anything wrong with me, except for extremely low circulating B12, I was given 6 initial B12 injections over a 3 week period and now receive quarterly injections as a top up.

As this is a sleep forum, I won’t go into all of the symptoms of Pernicious Anemia, as it’s called, but insomnia is one of them. I’ve had insomnia (probably DSPS) for about 10 years now. Initially I used to fall asleep through excessive drinking at university, which is obviously not very productive sleep. In the past couple of years my being a “night owl” has turned into N-24, having a day of about 24 hours and 30 minutes. It is virtually unbearable, as you can probably relate to.

After my initial B12 injection I felt euphoric! I couldn’t remember the last time I felt like that. More relevantly, I had the best sleep I’d ever had. When I woke up, I actually felt refreshed. Is this what it’s supposed to feel like!?! I thought my problems were solved and I would gradually recover to be “normal”. No such luck: 10 months later I feel a whole world better, but I still have N-24.

Pernicious Anemia is pretty rare in young people (I’m 28), usually afflicting the aged. As such, it is very difficult to find specialists and consultants; much like N-24. Because of this, I’ve been researching B12 and related topics ever since my diagnosis, some of which relates to sleep.

N-24:
It seems that the core problem is to do with melatonin metabolism: a lot of people use melatonin receptor agonists (Ramelteon), melatonin enzyme inhibitors delaying its degradation or just melatonin.

Partial melatonin metabolism:
Serotonin is acetylated to form N-acetylserotonin through the action of the enzyme serotonin-N-acetyltransferase (SNAT). Then via the enzyme hydroxyindole-O-methyltransferase (HIMOT) a methyl group is transfered from S-adenosylmethionine to N-acetylserotonin to yield melatonin (5-hydroxy-N-acetyltryptamine).

In my case, the methylation of N-acetylserotonin is the problem: B12 is intimately linked to the production of S-adenosylmethionine (S-ame), the universal methyl donor. Methylation, in general, could be a problem for others too. Do a search on google, it’s a pretty big topic. B12, Folic acid (B9), methionine, S-ame and betaine (TMG) are some good key words.

There are potentially hundreds of reasons how the metabolism of melatonin could be impeded: Physical reasons such as blindness, optic nerve damage, damage to the pineal gland, SCN or hypothalamus; enzymatic insufficiency; melatonin receptor mutation. Finding the route cause would help treatment considerably, albeit not very easy. A DNA test to find out the alleles of melatonin enzymes you have would be useful, if you can get one.

It seemed strange to me when some of you said that you have high serotonin levels, when serotonin is a necessary precursor to melatonin. But then it dawned on me that you might have mutations in the enzymes that convert serotonin to melatonin i.e. serotonin-N-acetyltransferase (SNAT) and hydroxyindole-O-methyltransferase (HIMOT), resulting in too much serotonin and not enough melatonin.

I’ve not tried taking melatonin or melatonin enhancers, but I do have a few queries about possible side effects: Long term use of melatonin could shrink or diminish the pineal gland, increasing the need to supplement with melatonin. Just like taking other hormones such as testosterone or thyroxine shrink the testes and thyroid respectively. Also, taking melatonin could act as a feedback inhibitor, increasing the amount of serotonin in vivo, which is obviously bad for people with high serotonin levels anyway.

serf

[Norway]

Gosh. (Yes, again. My favorite word, apparently.) I'm impressed with the research you've done. And I'm almost convinced to take another look at B12. The last study I saw pretty much ruled it out as having anything to do with DSPS etc.

I do use melatonin, and it helps. I've seen it suggested that it may reduce one's own capacity to produce it, but I'm not too worried about that. No evidence, really, just a suggestion. I've decided "So what?" If it turns out to be true, and that just means I have to take melatonin the rest of my life, OK, I'll do that.

Keep us posted on your research. It's interesting.

[serf]

I agree about using melatonin, considering the side effects seem pretty minimal when set against the huge advantages, hopefully. Where I post on another forum about B12 and elsewhere, people say that melatonin doesn’t help or makes them feel “strange”; probably because they are using too much or taking it at the wrong time?

I was wondering why ramelteon exist, when its action is similar to melatonin. Why not just take melatonin? Apparently “the affinity with which ramelteon binds to the MTI and MT2 receptors is substantially greater than that of melatonin itself, and plasma ramelteon levels after the 8 mg dose are at least an order of magnitude greater than those of melatonin after its standard 0.3 mg dose.” Extract taken from this paper: http://web.mit.edu/dick/www/pdf/1003.pdf. One thing I did notice was that “ramelteon 8 mg can apparently induce prolactin secretion in some subjects”. “Man boobs” could be a side effect of taking ramelteon long term.

The more recent studies about B12 and DSPS do seem to come to the conclusion that B12 doesn’t have any bearing on the condition. But there are other studies that say patients have “remarkable improvement”, although combined with other therapies. Most of the studies say that the action of B12 is unknown; but I’m virtually convinced that the mechanism is due to the synthesis of s-adenosylmethinonine. The mechanics are intricate, but there is definitely a link. The effects of B12 may not be as remarkable for people that have a decent methylation status in the first place, suggesting that there is something else “wrong” in the metabolism processes.

If you are considering taking B12 supplements, here are a few things to bear in mind: The toxicity of B12 is virtually none existent. Methylcobalamin, a form of B12, is likely a more effective coenzyme of B12 because of its reduced form (it’s a bit more expensive though). Most synthetic B12 is cyanocobalamin, having a cyanide group, as apposed to the methyl group of methylcobalamin, at the axial ligand, a more oxidized form. Oral B12 needs to be taken in “mega doses” to have any significant impact, due to the absorption mechanisms of B12. A typical tablet of 3000mcg of B12 is 50,000% of the RDA, but hardly any of it actually goes into the system. One good way to take oral B12 is to allow the tablet to dissolve under the tongue, where passive diffusion can take place. The best time to take it would probably be just before the time you would take melatonin. An injection of B12 into a muscle is the best way to increase levels dramatically, as it bypasses the absorption process.

I’ve only recently started reading up about circadian rhythm, and it seems that I’ve opened a can of worms. There’s already a load of information that I want to share with you. I hope I’m not repeating things too much.

The reason that light therapy works is due to melanopsin, a photopigment found in specialized photosensitive ganglion cells of the retina, separate from rod and cone photoreceptors. As well as the intensity of the light, the color (wavelength) is an important factor as well: melanopsin is most efficiently excited by blue light (420-440 nm); new light therapy lamps now utilize this spectrum of light. Signals from the activated melanopsin ganglion cells are then sent to the SCN of the hypothalamus. It occurred to me that blocking blue light in the evening could have positive results, just like increasing it in the morning. I did a few searches and apparently it’s old news: https://www.lowbluelights.com/index.asp.

“The core of the biological clock (central generator of the circadian rhythm) is thought to consist of interactions of approximately ten “clock genes”, including Per1/2/3, Cry 1/2, Bmal1, Clock, and casein kinase 1 delta /epsilon (CK1d/e) (7). Per1/2/3, Cry 1/2, Bmal1, and Clock code for transcriptional factors, while CK1d/ e code for kinases that phosphorylate these transcriptional factors.” Extract taken from: http://www.jstage.jst.go.jp/article/jphs/103/2/150/_pdf, where they even call non-24-hour sleep wake syndrome N-24. Variations in these genes probably account for most individual with DSPS and N-24.

More recently, “the work by Godinho, Maywood and colleagues identifies Fbxl3 as a new gene involved in the mammalian circadian rhythm and shows that the mutation Afh by disrupting CRY protein degradation, delays the circadian regulatory loops and, in this way, extends the circadian cycle of mutated animals. Now, using these results and by relying on the homology of mammals genes the next step is to find the corresponding gene/mutation in humans and its association with disease.” Extract taken from: http://www.sciencedaily.com/releases/2007/05/070510120713.htm.

Understanding what all of this means is pretty difficult. This website does a great job of explaining it: http://www.endotext.org/neuroendo/neuroendo15/ch01s02.html. The second diagram is particularly useful. I was going to write a simplified version, but I don’t think I would have done it justice.

What impact does this have on treatment? Well, finding out what “clock genes” you have would be a good start. It is obvious that these genes aren’t the only things responsible though; as I am proof of that (I assume my only problem is B12 related). There are people on my pernicious anemia forum who have chronic insomnia and thyroid problems, something which seems to be common. A quick search on the internet brought up a load of papers relating melatonin to the thyroid hormones triiodothyronine (T3) and thyroxine (T4). Getting a simple blood test can show you if you have a thyroid problem, or low B12 for that matter.

If you have problems with these “clock genes” or can’t find any other cause, tampering with the internal clock is probably the best route: The internal clock works through a negative feedback process, with regard to melatonin, and directly from light stimulation. So, factors influencing these two main inputs are key, as well as timing. Complementary treatments of morning blue light treatment, early evening B12 and/or melatonin (or other melatonin receptor agonist) supplementation and evening blue light deprivation are good places to start. Exercising at the right time could be beneficial as well, due to human growth hormone stimulation and its interactions, but I’ve not read into that yet.

Anyways, I’ve recently bought a therapy light. So far it seems to be working well. I hope it will last.

serf

[sassanik]

I probably have some sort of Circadian Rhythm Disorder, on top of my IH.

I use a light box, a goLite, and I find that it does indeed help me out! You can often get your health insurance to pay for it too!

I have been taking melatonin for the past month and it does seem to help me at this point. I am at least happier and more cheerful, even if I am tired.

There is indeed alot of information on these subjects online. Though I find it annoying that in general they don't know a whole lot about many of the sleep disorders out there.

IH just means that you are really tired and they don't know why. That is a pretty darned general term if you ask me!

I hope the lightbox helps you out! I get SAD in the winter (on top of my other issues), and it has helped me.

Sassanik

[serf]

Here's some research about serotonin inhibiting retinal input, as Eric Van mentioned previously: http://www.jneurosci.org/cgi/content/full/19/10/4034. High serotonin levels would inhibit synchronization in the morning, delaying the whole process.

serf