I guess what I was hoping to find that there is some sort of clinical manager for these people since so many have had so little success working through ordinary channels  I guess I've never heard of a specialist in sleep psychology.  Thank you so much for answering Shivani!

I suffered long sleep latency and/or insomnia. I found that I had an abnormal erythrocyte transketolase indicating thiamine deficiency. High triglycerides and inflammatory markers also suggested sugar ingestion. I stopped sugar in all its forms and it took six months to get the lab indications back to normal. This did not completely solve the problem but I found that biofeedback did and I can now sleep normally with no assistance.

Dear Susan. As a Pediatrician i often have to adress delayed sleep phase (DSP) in some patients of mine, mainly adolescents; what is indeed a difficult task as in modern life many factors contribute to DSP. I noticed that if not all the family engages in an attempt to solve the prob, its solution is very difficult . When melatonin; changing lifestyle;  and appropriate exposition to light fails...; and  the  family is not compliant i advise these patients to change their school hours to the afternoon period  whenever this is possible. I do not believe that there are biological reasons for the DSP to occur, My assumption is that  this important sleep prob origins only from an erroneous lifistyle  of the patrient and his family. One point i advise a lot is that the DSP patient cannot have great disparities in the  timing to sleep between school days ( or working days) and weekend days. I inform the adolescent  that only one weekend a month is allowed for him/her to go out and so delaying the time to go to bed; and whenever this happens i advise the family to wake up the adolescent in the same hour that  him/her have to wake to go to school every day. Having two social jat lags every week is one of most serious prob. that impairs DSP patients in having a good life quality and to solve his/her sleep "social" problem.  It is always necessary to addres restless legs syndrome whenever it is the case, because this syndrome frequently ensues DSP as a commorbidity. Greetings from José Carlos Pereira Jr. 

Jose, thank you so much for your thoughts on this. There are about 1500 people on a facebook group that say they have found that the standard solutions to correct sleep phase that you've mentioned haven't helped them a whole lot. I've heard that some of them say they do benefit from very low doses of melatonin but not from larger doses, which I thought was interesting..  I was hoping to find someone through my question who has looked deeper into genetic or metabolomic issues or who has investigated more of a biological rather than behavioral or social reason behind the issues in these patients   Perhaps we should consider that there could be two different conditions that look alike in how they are disruptive but which spring from different causes and maybe will have different solutions.  It is very interesting that you call this issue rather common in adolescence now. That makes me want to ask  some older retired pediatrician friends if they think it is new for this problem to be so common. Thank you so much for your detailed answer.

Susan here is a great article came from Cleveland clinic and based on a lot research that was done. Read this article as it provides very useful information about DSPS and how it might be treated.

http://my.clevelandclinic.org/services/neurological_institute/sleep-disorders-center/disorders-conditions/hic-delayed-sleep-phase-syndrome

Thanks

Asif

http://my.clevelandclinic.org/services/neurological_institute/sleep-disorders-center/disorders-conditions/hic-delayed-sleep-phase-syndrome

Go to:

www.circadiansleepdisorders.org

In my experience as a physician for people with an intellectual disability specialised in sleep problems, children with ASD present with sleep-onset problems (mimicking DSPS), but in fact melatonin release starts late and slow and stays low all night. Many of them are CYP1A2 poor metaboliser as well, so if treated with melatonin (only fast release!) you must prescribe a low dose (0,1-0,3mg). On higer doses they will develop 24hour high melatonin levels, which paradoxally result in more sleep problems.

 Hi Susan, if you want to go into details about the biology and the genetics behind DSPS you might contact Till Roenneberg: https://www.researchgate.net/profile/Till_Roenneberg

Thank you so much for the wonderful answers!   Wiebe, I am particularly interested in rhythms you may have found in autism and issues of low doses of melatonin.  My daughter has told me that lower doses do seem to have worked better in some that she has heard from on this DSPS list on facebook, so your experience in this area is greatly appreciated.  Christopher, I wrote Dr. Roenneberg, so thank you so much for this reference.  He has many interesting papers to study in this field, so I feel I have found a goldmine.  Many thanks!  And thanks all  of you for your insights and willingness to share them.

I have reviewd dossiers of ASD patients. Over 75% of my ASD patients with sleep problems are CYP1A2 poor metaboliser. Attached an Exel file on this topic. Almost all new patients who are on melatonin medication at first visit present with sleep maintenance problems and have high melatonin levels at noon. This is not the case in new patients who do not use melatonin at first visit, with the exception of children with Smith Magenis syndrome. In 40 / 76 non-melatonin users at first visit (52,8%) we found loss of effect and high day time melatonin levels after 4 – 12 weeks of melatonin treatment. I refer to my papers on this topic. I am writing a new paper on this topic.

Many thanks, Wiebe!

My studies in autism have focused less on Phase I detoxification and instead more on Phase two. Certainly, my experience is that much more attention is given to p450 enzymes than Phase II processes, especially in drug metabolism papers.

This paper suggests some other things to measure in melatonin :http://www.ncbi.nlm.nih.gov/pubmed/24446865

My first ten years studying autism was focused on sulfate (extending thoughts from Rosemary Waring at the University of Birmingham),but as the research on sulfate transport grew into an understanding of how the SLC26A family of transporters would also transport oxalate, that's when my work changed into studying the effects of elevated oxalate that we found in autism and that has occupied my last eleven years.  You can read that paper that is from the European Journal of Paediatric Neurology on my page if I didn't suggest that before.

I wonder if your continued work on sleep issues in autism could also include looking at sulfation, and glucuronidation of melatonin in this population.  It would be a nice addition to these wonderful papers you just sent. 

Oxalate may well become competition for transport and thus interfere with sulfation, and I am particularly interested in why people high in oxalate tend to wake up in the middle of the night, and are unable to get back to sleep.  That's not just in autism.  2:30 to 3 am is the magic hour for them.  What is going on in the pineal gland normally at that hour?

Kudos on some very interesting studies, and I am so glad you sent them.

By the way, do you by any chance have rs numbers for the cyp450 mutations you used for screening in your study?  That would make my life easier.

With gratitude,

Susan

Dear Susan,

I have the following numbers, hope this is wat you mean:

C_15859191_30 = rs2069514 = CYP1A2*1C

C_30634146_10 = rs12720461 = CYP1A2*1K

C_34816147_10 = rs72547514 = CYP1A2*3

C_30634246_10 = rs72547516 = CYP1A2*4

C_30634244_20 = rs28399424 = CYP1A2*6

C_8881221_40  = rs762551 = CYP1A2*1F

Wiebe

exactlly!  Many thanks, Wiebe!