Being non-verbal does not mean you cannot communicate; you can use sign language, you can write/type, you can use pictures (Picture Exchange Communication System – PECS) or you can use an augmentative communication device. Such devices used to cost a fortune, but now they are just apps you can install on a tablet computer or smartphone. These apps exist in numerous languages not just English, Spanish, German and French.
In 2007 we used PECS and started to use a special touch screen connected to a PC. Using special software, Monty could show that his vocabulary was much more extensive than we thought, even though he could not speak, read or write; it was all picture-based.
I just saw that one American study is suggesting that the incidence of DSM 5 autism is now 2.5%. I think this will inevitably mean less and less attention for those with non-verbal autism, which I suspect is still around 0.3% of three year olds.
Parents or the State?
Who should be doing something to help those who are non-verbal?
This question recently arose when I was talking to the family of an 8 year old boy with severe autism. He is non-verbal, but goes every day to a special school for autism. I asked if he is going to learn sign language, or is he going to get some other kind of means to communicate? Apparently not. I explained about augmentative communication devices and suggested asking the school about them, or just go and buy one. You do have to wonder what they are doing all day long in this special school.
There are many alternative methods to communicate, but they all require someone to teach them.
Whose job is it to choose a method and make sure it is implemented?
I guess this depends on where you live.
In my world, the proactive parent would start to do this by the time the child was three or four years old. Given not all parents are proactive, you would think that at pre-school or junior/primary school “the State” would step in and take some action; apparently not, at least where we live.
So what happens to little kids who have no means of communication? They become adults who have no means of communication and, not surprisingly, they will have major behavioural issues.
Non verbal vs non conversational
Whilst on this subject, there is another important issue to highlight. Even when some people with severe autism do start to talk, they very often do not become conversational. They can answer questions and make requests for items they want, but they do not become chatty like typical kids.
Some parents refer to their non chatty child with autism as being non-verbal, this really is not fair to those children who do not have a single spoken word.
Some children with autism can sing but do not talk. This may sound very strange but both Monty's assistants also participate in musical/theatrical group of kids with autism that puts on public performances. They have such kids.
I think if you can sing, you can be "trained" to talk. It is just requires a lot of effort by someone - parents, therapists or school assistants.
Becoming more conversational is a continuing challenge in educating a child who was non-verbal. I have a big pile of books and training manuals on this subject and recently decided to re-emphasize this in Monty's daily schedule. We cut back on physical education (PE) at school and one after-school piano lesson. We already cut out the two foreign languages at school to make time for 1:1 work with his assistants.
By encouraging longer answers to questions both spoken and written, there is also a net benefit to regular school work.
Studying Severe Autism
Researchers tend to avoid studying severe autism, which often also means non-verbal autism. Research is focused on what I would call Asperger's and what researchers would call level 1 autism; in DSM5 terminology there are 3 levels of severity. Clearly it is much easier to study people who can hold a conversation and have a typical or even high IQ.
There is an initiative, see below, to study severe autism, but for drug producers the big market is mild autism. You can see this by looking at the types of drugs currently in clinical trials.
What Can We Learn from Studying Severe Autism?
Non verbal vs non conversational
Whilst on this subject, there is another important issue to highlight. Even when some people with severe autism do start to talk, they very often do not become conversational. They can answer questions and make requests for items they want, but they do not become chatty like typical kids.
Some parents refer to their non chatty child with autism as being non-verbal, this really is not fair to those children who do not have a single spoken word.
Some children with autism can sing but do not talk. This may sound very strange but both Monty's assistants also participate in musical/theatrical group of kids with autism that puts on public performances. They have such kids.
I think if you can sing, you can be "trained" to talk. It is just requires a lot of effort by someone - parents, therapists or school assistants.
Becoming more conversational is a continuing challenge in educating a child who was non-verbal. I have a big pile of books and training manuals on this subject and recently decided to re-emphasize this in Monty's daily schedule. We cut back on physical education (PE) at school and one after-school piano lesson. We already cut out the two foreign languages at school to make time for 1:1 work with his assistants.
By encouraging longer answers to questions both spoken and written, there is also a net benefit to regular school work.
Studying Severe Autism
Researchers tend to avoid studying severe autism, which often also means non-verbal autism. Research is focused on what I would call Asperger's and what researchers would call level 1 autism; in DSM5 terminology there are 3 levels of severity. Clearly it is much easier to study people who can hold a conversation and have a typical or even high IQ.
There is an initiative, see below, to study severe autism, but for drug producers the big market is mild autism. You can see this by looking at the types of drugs currently in clinical trials.
What Can We Learn from Studying Severe Autism?
I read from several sources that the life expectancy of autistic people is around 35. This goes especially for non verbal ones, which are unable to tell their doctor about unrelated conditions and issues they suffer from. This was a handy reply for me while my kid was non verbal, when people asked me how I could try out unofficial therapies on my kid. Peter, i have a practical question. When I look at my daughters behaviours, I try to group them according to phycial problems they most likely stem from. Example: raging - allergies. I am unable to deduce what scripting is connected to. It is of course a mechanism connected to anxiety but I don’t think its only that. What are your ideas? my daughter is both more communicative AND more scripting currently. she also got into the habit of getting stuck in a phrase. For example she will look at toys in the shop and start repeating ‘Grandpa Pig’ despite this being completely unrelated. I just tell her ‘Hey!’ and she then stops and looks at me to see what i wanted. I cant figure out what this means.
ReplyDeleteSome people see scripting (repeating specific words/phrases) as a form or stimming/stereotypy, in which case whatever works for stimming would help. In our case NAC reduced stimming and constant requests for what is happening next.
DeleteI think scripting is likely a form of self-comforting. Certain words just make that person feel better. It is quite rational, just like singing makes many people feel better. The scripting will change over the years, but the comforting effect of the repetition remains. I do not see it as a problematic behaviour, as long as it does not get out of control.
If you spend enough time with your daughter, you may well start scripting yourself, perhaps just at home. Within limits, it can be an endearing feature of autism. We once struggled to find where Monty had first heard the phrase he was scripting, when we found which episode of which cartoon we felt better.
One way people with moderate to severe autism learn to talk is hypothesized to be the result of them both missing the developmental window for learning phonemes and language structure, as well as having deficits in the lateral orbitofrontal cortex which helps string phrases and sentences together in a bottom up process. So as a compensating mechanism, it is hypothesized many people with autism will learn scripted speech and then try and place it in the appropriate context and break it down as necessary over time into context appropriate chunks so that some of the higher-level individuals are eventually able to be able to hold a conversation with this method even though to most people the speech may not sound fluid or natural. Think of it as not being able to generalize language as most humans do effortlessly, but rather noticing where words belong in a conversation for a specific context and then using them accordingly based upon feedback given to the person as to whether they are using the words correctly or not. ABA for all its many flaws may benefit a minority of higher-level autistics through the brute force of building up this scripted vocabulary in individuals, especially as some of the more modern methods of ABA like pivotal response training which allows the person with autism to work on what they are most comfortable with given a set of choices may allow them to test this vocabulary in a sandbox they feel confident to learn in.
DeleteHi Tatjana,
DeleteThere was a period of time where my daughter would repeat the same phrase over and over again, and many times, she would also repeat the same short songs (e.g. 5 little monkeys, there were 10 in the bed, the itsy bitsy spider, etc.) over and over again.
Interestingly enough, as her speech has been improving, she has been less repetitive in her phrases / songs.
Tatjana, if I may ask, have you had a genetic diagnosis? You don't have to share what gene, but I was curious to know if you have had a genetic test and if so, if you've had a relevant gene identified.
AJ
P.S. Grandpa Pig … Definitely Peppa's (and George's) grandpa ;-)
No, we have not done anything in that field other than a maximized genetics test which shows a limited number of genes which they think has research to back it up. I am also not all to concerned about that. My idea is that whatever she has, genetically, anyway has to be fixed with non/genetic cures. I am more interested in finding out what is wrong with her metabolism and organism in the functional sense than knowing what caused it in the hardware. Btw its Peppa all the way. Its her obsessive interest but as they go its a perfect one because Peppa does all the stuff small kids do and my daughter learns a lot about the world that way. We hope that ina year we will have achieved de-Peppisation :-).
DeleteTyler, this is exactly how my daughters learning process looks like. She has however discovered some language blocks independently of scripting - such as the concept of ‘I’ or the concept of things and people having individual names apart from having a generalized category they belong to. We have TMS in the pipeline and I am hoping that this will help her on that front too.
DeleteHi Tatjana,
DeleteThe reason I was asking was that if you have some success with TMS, it would have been interesting to be able to associate a specific gene (or pathway) to benefits from using TMS.
We appear to be having some good improvement with BHB / MCT, and it looks like there is a dose dependent improvement, so we continue to titrate up and use keto test strips to see where my daughter is at.
As far as Peppa - yes, when that was my daughter's favourite, we were very happy as it's such a sweet cartoon. Now she's into My Little Pony / Equestria Girls ...
Have a great day Tatjana!
AJ
I spoke at length with the doctor about TMS and from what he tells me, and I am truly paraphrazing and giving my impression of this conversation, but I honestly think that was his gist - TMS is not a very ‘precise’ method. I don’t think it has to do with genes whether it works or not, I think its a mechanical ‘fix’. If you look at data coming out of the Duke stem cell trial, you will see that they think that a specific EEG abnormality is the predictor whether a child will have gains from it or not, and the gains seem to be in a specific type of improvement in the EEG. What i am trying to say, whatever the genetic causes, there is a lot of technical fixes you can apply. Most autism specialists will request a genetic test, and MANY other tests such as the OAT, Mitoswab, Cunningham panel, AND family history AND symptom list in order to be able to point out where in the organic mechanism we call body is a place to tighten the screws. Just knowing what the ‘hardware’ is, will in my opinion not get anyone far.
DeleteYes, many a time we were able to enter her world and develop amazing play by knowing what scenes she is acting out. I am not per se afraid of the scripting, I would just like to connect it with a speccific process happening inside. I have a consult these days with somebody about her which will likely yield more info about what to do to reduce that. I was able to connect with a local neurologist who js well versed in TMS (for other purposes) and he is willing to try it on her too. So we will see about that too jn the coming months.
ReplyDeleteThis comment has been removed by the author.
ReplyDeleteHello,
ReplyDeleteI have a question which I will post here:
what do you think about folinic acid and
CSF 5MTHF? I am in a facebook group where they brought this article:
https://www.ncbi.nlm.nih.gov/pubmed/30448717?fbclid=IwAR1L0jHk23bwmhxJLsQ-Rix8Yo0D1kwCKJjO0xw3RhRvKBWynthOAOIUt0A
I saw you can buy 5 mthf in Amazon.
Thanks,
Regards
Our daycare usually has an advent calendar every year for the (NT) kids, with some pedagogic twist. This year every day contains a new sign (as in "sign language") or a song with corresponding signs.
ReplyDeleteWe are indeed very lucky to have our daughter in such an including place.
/Ling
Does anyone know if Nicotinamide Riboside block SIRT1 just like plain Nicotinamide does?
ReplyDelete/Ling
No Ling, it does the opposite. I assume you know the difference between Niacin and Nicotanimide which are important distinctions when supplementing B3.
DeleteI am very much in the learning phase with regards to how mitochondria and anything related works, and I feel pretty thrilled! By the look of your, Peter's, Agnieszka's and AJs comments you have all been into this area before me.
DeleteAnd no, I really don't even know the basics yet, so don't assume I know the difference...
I recently found one of your old comments Tyler where you discuss how in autism, not only those with mutations in the mitochondrial DNA (or the electron transport chain) can have mito dysfunction, since many genes in the nucleus also code for things in mitochondria. In that comment you pointed out how hard it would be to know of the latter case.
But it looks like "my" gene actually is one of those that localizes in the nucleus and regulates a protein in the mitochondria: Heat shock protein 60; Hsp60.
What I've learned so far is that the heat shock proteins help clearing out misfolded proteins like tau and Amyloid-beta. They do this through the Unfolded Protein Response (UPRmt), which is the step coming after the ETC and also seem to be the bridge from ETC function to prolonged lifespan/healthspan. But this is not the only thing the heat shock proteins do. They are highly related to (auto)immunity, Th1/2 balance, gut issues, obviously cancer, atherosclerosis, diabetes, HDACs and mitochondrial mass. They act like "danger signals" to stress, a formulation that makes me think about Naviaux.
I remember Agnieszka having a question a long time ago about heat shock proteins, so maybe she knows more than me.
The related Hsp70 and Hsp90 can be modulated through the PKA pathway with resveratrol, pterostilbene, eventually forskolin and sodium butyrate (but possibly in the other direction for NaB). Maybe something for you AJ to look up?
Aspie1983, I now see that you have big effects with supplements targeting mitochondria. How could I not see that before?
/Ling
And to pose some kind of question: My concern at the moment is if I want to up the UPRmt or not.
DeleteIt looks like too little Hsp60 makes the UPRmt go on "continuously" (working ineffectively?) which is bad. A consequence is that mitochondrial mass is reduced.
I know that the UPRmt can be activated by supplementing with nicotinamide riboside or plain nicotinamide that raises NAD+, but I don't know if more UPRmt would be good or bad. High doses of Niagen can cause weak muscles, and my daughter is already hypotonic and non-energetic. I know pterostilbene has a good effect on her cognition, and it raises SIRT1, but I don't know if those two facts are related. If they are, I wouldn't want to inhibit SIRT1...
So, I would like to implement some kind of mito stack/cycle to test how much this contributes to my daughters health/cognitive issues.
Maybe some PQQ for more mito mass first? I'm adding in ALA this week.
/Ling
Never heard if Niagen causing weak muscles from too much NAD+, but then again my son as well as I have only ever done the standard dose except before a half marathon in the hopes of avoiding leg cramps on my bulky frame. Nonetheless, I still got leg cramps near the end of the half marathon but it is not suprising since I barely trained for the race that year. Anecdotally it does seem to help a bit with skin tone and it dramatically decerases the level of soreness following intense wxercise.
DeleteTyler, I think it could be correlated with high doses of Niagen, either inducing so much mitophagy that mitochondrial density goes down for a while or possibly that the size of the mitochondria gets smaller by fission, and therefore you get less ATP out of them. I guess the idea here is to cycle high doses instead of using small doses constantly, for some benefit in certain areas.
DeleteThere was a couple of interesting threads by people at the longecity forum trying different protocols for flushing out damaged mitochondria, building new mitochondria, increasing mitophagy to get out more from low-level exercise or fusioning mitochondria.
I think it's fascinating that there are so many ways you can regulate these things.
/Ling
Mitochondrial fission and fusion is something that happens on its own so there is nothing really good or bad about one or the other as it is just how they work. one unique thing about neurons is the size of mitochondria in the soma is different than the size of mitochondria in the dendrites and axons. The size is different because the mitochondria in the periphery of the neuron not only function to produce ATP, but also acts as a potassium sink that helps to regulate potassium flow at the synapse.
DeleteI don't think too much Niagen will cause excess mitophagy because there is a ceiling to that process. People have taken insane amounts of regular B3 in the form of Niacin and never died. The only real theoretical downside is that cancer cells like normal cells are hungry for NAD+ and will upregulate the salvage pathway to support their metabolism. In fact a very recent paper I read in the last week or so used metformin which inhibits NAD+ production and another drug which prevents cells from using lactate for energy as a one two punch two disrupt the metabolism of cancerous cells. Of course immune cells are very NAD+ hungry as well and a poorly functioning immune system will allow cancer to spread as well so whether to increase NAD+ or not is very situational. After all, younger people have a higher NAD+/NADH ratio but also have lower cancer rates than older people.
Tyler, I am not totally convinced that mito fission/fusion just "happens" - it is a response to things like stress, UV irradiation, starvation and Ca2+ inflow through NMDArs.
DeleteIf mitochondria for any reason is forced long-term to hyperfission/-fusion it would intuitively be a bad thing.
"Mitochondrial hyperfusion [..] is thus thought to buffer the potentially deleterious effects of stresses [..]
In the case of starvation, hyperfusion has been proposed to protect mitochondria from autophagic degradation or mitophagy [..]
mitochondrial hyperfusion also serves as a homeostatic response to maintain ATP production in cases where complex IV of the ETC is impaired. The hyperfusion response, however, is
transient and thus cannot buffer long-term defects in ETC activity."
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4075653/
I don't know if interventions trying to balance up the fusion/fission rate would be a good idea, there are probably good reasons for the body to react in this way.
But some people think that using a protocol where these two + other activities are promoted in sequence is a good way to promote healthy and effective mitochondria and get rid of defective ones.
I wish I had better sources on this topic, but I don't. I have yet much more to learn.
/Ling
On the subject of mitochondrial fission/fusion:
DeleteSulforaphane is a Nrf2-independent inhibitor of mitochondrial fission
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5126150/
/Ling
Hi Aspie 1983, I will make another trial with memantine and keep a 2 mg dose per day.Why did you stop it?
ReplyDeleteValentina
Valentina, I did multiple long write ups on it to why I discontinued and also the after effects. I believe it can potently affect the immune system. Also amantadine (very very closely related) is actually an antiviral and a study I cant find atm but it exists (multiple aswell) show that memantine does have an effect on the immunesystem to a fair degree.
ReplyDeleteYou should do a search on memantine, you will find my posts for sure.
Thanks Aspie,even at the 2 mg very low dose, may be I will not take the risk.Memantine may acivate dopamine D2 receptors.
DeleteValentina
If you do try it, start very low indeed Valentina.
DeleteI weight around 90-95kg and I thought 5mg was a very strong starting dose. I can imagine someone like myself would have been better off with a 2.5mg starting dosing.
A child (obviously far less body weight) pherhaps 1.25mg. Also like you said memantine does act on dopamine, wikipedia states that its affinity for d2high is even higher than its nmda antagonism.
Would like to add that the mental effect on me atleast was very positive, it actually obliterated my stimming/tourette, keep in mind I believe that my obsessive behavior and thus self stimming and tourette symptoms are probably due to sertonin imbalance and somewhat low dopamine.
From all the extensive reading that I have done on memantine in adults is that the mood effect is pretty much all positive, everyone seems to become more outgoing on it, however I can also imagine it might make some kids more likely to act on their impulses.
It does not seem to make people (nor me) aggressive though, in fact the oposite I found it to have potent anti-aggressive effects.
It is confusing Aspie 1983,I thought that tourette and OCD happened due to increased dopaminergic activity or high dopamine or dompamine supersensitivity, not low dopamine.I know Iam oversimplifying because this theme exceeds me. The fact that memantine has obliterated your stimming/tourette like symptoms considering its high D2 dopamine affinity,it is impressive.I read a study that said "baseline striatal D2/3 receptor binding in TS and OCD was decreased, supporting the hypothesis of chronically increased dopaminergic activity in both disorders.
DeleteValentina
Yes Valentina that is also what I have read, however just as with autism there are multiple 'models'. 23andme points towards TPH2 (tryptophan hydrxylase) as the gene candidate in my case for tourette/repetitive behavior.
DeleteMy experience with modulating stratial dopamine (inositol, alpha gpc, piracetam) is that they do induce dramatic alterations in my daily behavior (less focussing on not important things and less ritualistic behavior and more behavior flexibility). My experience with tourette/repetitive behavior is that it is a form of coping with stress. We know that there is a very atypical stress response in autism.
One thing that I would like to add is that after the crazy chemical antipsychotic cocktails that I had to take during puberty (thanks mom and dad...) is that it not only seemed to have aggrevated the anhedonia, but also a that my tics/repetitive behavior went from the impulsive type of tics more towards restricted interest. I barely do the 500 times per day trouser lifting anymore now for example.
Memantine took away all of my worries, I guess deep down inside Im a very worried and pherhaps insecure person due not being able to properly handle daily stressors properly.
I hope people dont take it too hard btw when I talk about my antipsychotic experiences and ssris, but its true (atleast in my case) that it seems to have permanently altered/rewired my brain. I was actually quite happy as a kid/teenager in the pre-ssri and pre-antipsychotic days, they did a 180 flip on my personality.
Once more regarding dopamine in the brain and memantine, a lot of drugs (memantine included) increase dopamine only in certain brain areas where as it leaves them untouched in other areas.
Memantine mainly seems to act through VTA dopamine (this is part of the mesolimbic pathway) and also the reason why extremely high doses of memantine can have reinforcing properties.
Reuteri atcc 6475 also activates VTA dopamine, this is necesarry for proper social functioning, wanting to see friends/family, forming relationships with people.
Another example is aripiprazole which is neither classed a dopamine agonist nor antagonist (yet has the properties of both), it is an atypical antipsychotic. It can raise both dopamine and lower dopamine depending in the individual and the brain area. Its one of the meds that I would still like to trial some day, it increases dopamine in the caudate, this is the part of the romantic 'hotspot'/part of the 'liking system'. I think aripiprazole is one of those meds that the only way to find out what it will do for an individual is to try it.
Valentina if your son is allready very outgoing/happy/energetic by nature there is the chance that memantine might make him hyperactive indeed. However if you feel he is often down/lacks reward from social interaction with friends/family then it might help him. As with all meds though, there is a benefit/side effect ratio, no med is perfect unfortunetely.
Aspie 1983, my son has hipotonia, would say not energetic but yes a bit hyperactive. He has manias, some tics and rituals and lately an extreme anxiety, he needs to grab any object, he joins and hide them. He is cheerful and sociable with friends and enjoys going to his grandmother's house and listen to her stories.He always wants kisses from me or his father.But he has all kinds of fears. Do you think he would be a good responder of memantine?
DeleteValentina
Aspie1983, do you have some kind of "gain-of-function" of TPH2 then?
DeleteAs you mentioned worries about future colon cancer, you should really look at any substance that targets L-LTP:
Berberine
Resveratrol
Curcumin
Bacopa
Krill oil / EPA
Ginseng
Luteolin
Taurine
Fisetin
Progesterone
Forskolin
Green tea polyphenols
NSAIDs
/Ling
Ling, Im not sure what you mean by gain of function, might be ither be my own stupidity and autistic traits or language barrier as english is not my mother language.
DeleteMy 23andme data (ran through codegen.eu) says the following:
https://ibb.co/sv04NkD
https://www.snpedia.com/index.php/Rs4565946(C;C)
https://www.snpedia.com/index.php/TPH2
'rs4570625 and rs4565946 in TPH2 linked to the pathogenesis of early-onset Obsessive compulsive disorder'
Its probably the combination of multiple genes that gives tourette/repetitive behavior though.
As you can see from my data that I have printscreened and uploaded to imgbb that I also have the cell adhesion allele that is associated with autism, aswell as the autistic oxtr allele (though there is some controversy that A:A is even worse than A:G).
Regarding colon cancer and other forms of cancer, yes Im concerned, I have multiple genes that show a fair bit of elevated chance to develop cancer down the road, please note that is not to say that I will actually get it, but it highlights the importance for me of leading a healthy, stress free life and an individually fitting diet is part of that.
Hence my focus on the gut (got around 15 crohn genes that show pretty elevated chance to develop it, which is interesting as you know my mother has it and my food sensitivities are very real - I get gas within 5seconds, literally when someone lights up a cigarette near me). This has tought me the extreme important of listening to the gut, both to food and environmental sources.
Also im sure that in my own case I have some kind of AHr mutation (I have 1 slow cyp1a2 gene as I showed a few weeks ago, and the studies I posted showed that in combination of having this gene + autism = sleep problems and melatonin production/breakdown problems).
Of the above list you posted I tried most of them, yet NSAID's are absolutely the devil. Even when I got the flu I do not take them, it literally feels as if they burn holes in my gut.
PGE2 in the gut is needed for mucosal smearing/gut integrity and other gut homeostasis. COX-2 is an interesting target, also considering the fever/autism connection (which is atleast 90% due to altered immune signalling/il6/pge2 signalling).
Berberine is something I will not try, too much interactions, imo it should not even be considered a herbal it is very powerfull. One interesting thing I found out the other day though is that berberine its antidepressant effect is due to it acting as a sigma-1 PAM, which is quite unique). However berberine can have so many interactions, if someone was to read it and wanted to try it, my recommendation would be please please use it standalone.
Panax ginseng = i respond very well too.
Taurine = great for relaxation
krill oil, well it felt too manic, was very impressed by how potent it is, probably due to the unique phospholipids/sphingomyelins present in it and bound to DHA.
curcumin my stomach cant tolerate and its a cyp3a4 inhibitor (I respond very bad to cyp3a4 inhibitors)
Resveratrol I never tried but would like to one day.
Green tea gives me headaches, black tea is very soothing though and antistress for me.
Forskolin, tried it a few times as part of CILTEP stack, could swear I gained a lot of moles on my arms/face while on it, so discontinued. Luteolin also was part of that 'stack'
Progesterone I recently got tested btw, I forgot to post my labs, but I was actually hoping it was low (so I had a target) but it was not.
DeleteHere are my most recent labs, as you can see all my hormones are actually ok for my age.
https://ibb.co/fDwN5hW
https://ibb.co/tJsqZvt
Also @Peter, in comparison with a year ago you can see (if you remember) that my urea is still decreasing yay! and it indeed correlates to me mentally feeling good, I strongly believe this is due to cordyceps and making the switch from mixed cardio/strength training 3 times per week in total, to nearly always 3 times cardio only. Breathing has improved, mood has improved.
Diet wise I only eat 3 meals a day now instead of 4-5 in the past (same calories).
Also if you look at my HDL, this has drastically improved compared with 2-3 years ago, I was at 1.1 then, my labs are always showing 1.5/1.6 now (im 99% sure this is due to coq10 which I am and have been taking, neither ashwagandha, cordyceps or any other herbal ever raised my hdl btw, only coq10 does).
Also liver is improving, I was at asat/alat 50+ and 50-60 around a year ago, and while I did these bloodtests I was not on nac nor sulforaphane and Im feeling even better now while on sulforaphane compared to when this blood was drawn, im pretty sure (by monitoring how I internally feel) that my asat and alat is now inside the healthy range.
@Peter my urea levels are also the one and only reason ive been so scared of starting bumetanide, I know your an expert on it and you also know that one of its main side effects is that it raises urea.
Some people with adhd that I have met on reddit and talk to a lot I have directed to your blog and it seems the inattentive ADHD (also called ADHD-pi) that is often characterized as a low glutamate/nmda malfunctioning subtype of adhd seems to benefit LOTS from bumetanide aswell (for their anxiety and social functioning).
My goal for the new year is that once 2019 is done that I will permanently make a decision on what meds/supps I will be on for life. As much as I keep striving for improvement/researching the subject I also note that it has become an obsession of its own.
I will probably settle for a combination of topical magnesium, vitamin c, low dose zinc, ginseng, cordyceps, reuteri, sulforaphane as herbals and im looking into aripiprazole, tianeptine (sert activator and adenosine a1 ligand) and bumetanide/pot. bromide as main therapy.
Weekly 're-feeds' I will probably do every sunday of the week where I will take low dose precursors, such as glycine for vasopressin/glutathione synthesis.
One of the most striking things in my entire journey is that when certain meds/herbals improve my social functioning my motivation and getting rid of my anhedonia automatically improves too.
Hi Aspie, the "gain-of-function" of a gene means that it is "enhanced"; for a receptor it would mean that more is flowing through it. I merely wanted to know if you needed more or less functionality.
Delete/Ling
Hard to say with 100% certainty Ling, but panax ginseng and caffeine (which both inhibit exercise induced TPH2 elevation to a large degree and thus serotonin synthesis) seem to help a lot for my mood and emotions.
DeleteSerotonin is complex, on 1 hand I seem to benefit from 5ht2a activation/upregulation and on the other hand too high serotonin overall seems to make me arrogant. There was actually research done on psychiatric disorders where in some cases individuals with very high serotonin committed the most gruesome crimes (due to complete lack of remorse).
While extremely low serotonin induces depression/feelings of defeat, extremely high serotonin definetely has the potential to aggrevate apathy.
Im thinking of trying tianeptine next year (which is hypothesized to be a SSRE, the oposite of a SSRI basically)
Peter, have you ever looked at something called REST? Just found this and it just looks important
ReplyDelete"During normal postnatal development, REST orchestrates the developmental switch in several key synaptic and extrasynaptic proteins including the NMDA receptor (NMDAR) and K-Cl cotransporter KCC2. (..)
REST binds and epigenetically remodels the grin2b promoter (gene encoding the NMDAR subunit GluN2B) and thereby silences GluN2B expression. This, in turn, promotes the switch between the immature (primarily GluN2B-containing) and mature (primarily GluN2A-containing) NMDAR phenotype at hippocampal synapses
(..)
GluN2B expression restricts synaptic incorporation of AMPARs
(..)
During early postnatal development (∼P8), NKCC1 expression decreases and loss of REST from the Kcc2b promoter induces upregulation of KCC2. (..)
Thus, REST regulates the sign of GABA (and glycine) synaptic transmission."
https://www.sciencedirect.com/science/article/pii/S0959438817301083
I think REST is inhibited by retinoic acid at some point.
Ling
Ling, I have not covered REST. It clearly does play a role in some autism. There is a nice graphic below.
Deletehttps://www.kyushu-u.ac.jp/en/researches/view/31
Many things seem to influence the GABA switch and so KCC2/NKCC1 expression.
I will cover it in a post in 2019.
I look forward to that post, Peter, very much.
DeleteBy a quick glance REST looks like a "holy grail"-thing or something for neurodevelopment.
I think REST must be related to RELN (reelin) somehow because they both seem to respond to retinoic acid and maternal care, and both are involved in the NMDAr subunit switch. One of them probably regulates the other.
The reason I found out about it was because I was researching miR-9-2 (not the miR-92 that regulates KCC2 translation, but possibly a cousin) and found its transcription was inhibited by REST.
As a sidenote... I want to tell you how pleased I am to hear that you are continuing your blogging efforts next year. One of my greatest fears are that your interest in the subject will weaken as Monty gets older.
Ok, now I said that out loud.
/Ling
Ling as far as I know chromatin remodelling (beneficially) changes during inhibiting hdac? such as with butyrate/sulforaphane and possible also ketogenic diet, due to BHB flowing around the body in very elevated amounts compared to none-keto state.
DeleteHi, Peter - we did 1mcg per kg Clonazepam for 10 days with no effects whatsoever. Its hard for us to organize it, since a friend makes it for is and it lasts 15 days as a solution, so we need him to make it every 15 days. Do you think we should continue and look for effects or is that it if there werent any?
ReplyDeleteTatjana, due to the long half life it takes 3 days to reach a stable level in your blood. If your dose was above the effective dose you could have seen the effect on day 1 or 2, but you might have missed it.
DeleteIt is unlikely that you are below the effective dose, but you could try a higher dose just in case.
The effect is immediate once you reach the effective dose range and slightly too much gives a sharp negative response. I started with too high a dose and only when I stopped did I see the effect as the level in blood was falling.
I think it is most likely that your child is not a responder. But you could vary the dose just to make sure.
Two doctor readers of this blog did find it worked and the dose was 0.6 to 1.0 mcg/kg. Not everything always comes to a fixed /kg dose and your child is young and I suppose not many kg.
She is 20kg. There is really no effect. First of all I do not know how you dose by 1 mcg, what we did was ask for a solution where one drop was 20mcg. So it probably anyway varies daily by a few mcg. I really dont know how else to make the solution.
DeleteTatjana, my method is very simple, I have a glass bottle with 100ml of water to which I add 0.5mg of clonazepam. I mix it well, since it forms a suspension, and I use a syringe to measure out 7ml. Keep the bottle in the fridge. At the start I was using 10ml, but over time it seemed to need less, certainly not more.
DeleteI use an electric frappe mixer that fits inside the bottle to thoroughly mix.
I have been doing it for so long that when travelling I scrape a tiny crumb from a tablet by eye, so as to avoid liquids and fridges.
Do children who have never spoken a word by age 8 still have some chance of learning to talk some day (maybe in their teens or even as adults) ? Or is it game over (as far as speech is concerned) for them ?
ReplyDeleteHelp !
GRT, it is never game over, but it does become less likely the older the person is. The important thing is to develop some method of communication, rather than just wait hopefully for speech to emerge.
DeleteHi Peter
ReplyDeleteI want to thank you for your tremendous work that you do here on your blog. I am still very scare to try medicines on my 6 years old severely autistic daughter without a doctor supervision. We live in French Canada and doctors here do not believe that autism could be treatable. I consider myself very lucky that I find you.
What I have try inspired from your site: potassium and NAC
We found potassium in powder (citrate and chloride), but even a tiny amount has a very strong taste and never M has been able to take a full dose.
With NAC we were lucky that she accepted right away. She took 3 boxes of PharmaNAC 3 tablets/day without any effect. So, we decided to stop it and try it again another time.
I read that for people for who NAC is not working a good try is l-carnitine/l-carnosine. We redid a blood test a few weeks ago because she tested low in carnitine and high in uric acid. We still have waiting for results.
What we give to her: mg, ca, Zi, iodine, B12, B6, Complex B, folinic acid, Se, Probiotic, Cranberry extract, TriEnza enzyme, Vitamin k, Vitamin D. All of this we have give to her for years because she refuses to eat. She eats only bread, dry cereals and Oasis juice with orange and carrots. For years we did food therapy without any result. Since last summer she has begun to eat fry meat (any kind) For years she did not eat any protein or fibre because of her food rigidity.
Her pediatric doctor recommended only Centrum Junior multivitamin. This is not enough for the RDA for her age. So, we give her each those enumerated above. We give her also melatonin 0.45 mg in school nights (dr. recommended 3 mg). For years we have gave her laxaday for constipation as our pediatric doctor recommended. We stopped it few months ago when we discover Probiotic, Cranberry extract, TriEnza enzyme.
What we try as advised by a naturopath: GABA, DMG, TMG and 5HTP. We saw improvements very quickly after GABA, better eyes contact, more attentive, begins to say same words when she sings. Improvement stopped after a few months. 5HTP gives nothing (we still try –first dose on 21 Dec 2018 -50mg/day). DMG and TMG did nothing also (we still give her TMG).
My daughter main autistic symptoms: non-verbal (now cc 50 expressive words and only 10 words in right situation); stimming talk (self talk – delayed echolalia); a lot of jaw stimming; limited receptive language (now cc 300 words), limited understanding, food rigidity (food phobia); obsessive compulsive disorder and sensory processing disorder.
This is our child portrait before to dig more in your site and make some decisions in biological/medical approach without a doctor advice unfortunately.
God bless you for your hard work and your decision to share this with us.
Prada, it would be worthwhile to rule out a single gene cause of autism; while this accounts for just 10% of all autism it is much higher in girls with severe autism. In North America you can arrange whole exome sequencing (WES) or a less expensive sequencing of just the known autism genes. At the University of BC in Vancouver you have the clinicians behind treatable ID. In severe autism the biggest issue is usually intellectual disability (ID).
ReplyDeletewww.Treatable-ID.org
If your daughter does not have a syndromic kind of autism, she has a 30-50% chance of being a responder to bumetanide. If she is a responder you would see a major improvement in 2-4 weeks.
Hi Prada,
ReplyDeleteIt might be a good idea to try l-carnitine for several reasons. It's potential for constipation relief would be one of them:
https://www.ncbi.nlm.nih.gov/pubmed/28366991
"The severity of constipation was significantly relieved after carnitine supplementation"
This study did not target children with autism, but there is also evidence of l-carnitine positive effects in ASD as well.
Apart from this one particular aspect, I totally agree with Peter to look for medical diagnosis in severe autism, be it genetic, neurometabolic, autoimmune or other.
It is not easy to get proper diagnostics in autism anywhere in the world. I recall I once stopped using the word "autism" at all and described my son as a child with "developmental issues, cognitive regression and involuntary movements". Paradoxically it worked.
Getting medical diagnosis years after autism label may be emotionally challenging so to speak, but can really help.
Thank you, Peter, and Agnieszka. The therapists around M do not see any intellectual disability. She learned vocals at 3 and toilet trained at 3 and a half; all alphabet and animals' sound at 4; numbers (1-20), colours, forms, body parts at 5; now at 6 matching quantities at numbers (1-10) and we work letters’ sounds and prewriting (she does not have any draw skills although normal motor skills), traveling to school on school bus, etc. I am very new to medical treatment. I have ordered acetyl l carnitine in powder and I intend to start with 50 mg and go up low and slow until 1 g (I have read that 50 mg/kg bodyweight) it is a good stop for L-carnitine. I have read also that acetyl l-carnitine is more absorbent, and I am not so sure about the 1mg dose for a 21kg, 6 years kid. Do you have any idea?
ReplyDeleteWe did a Rett test a few months ago and still waiting for the result. At a next appointment with our pediatric doctor I will ask about autism gene test, but I do not see her make a reference for that. If she does not I will look elsewhere.
You do not know how much I appreciate your comments!
Prada,
ReplyDeleteI am happy to hear your daughter has no ID. I mentioned the carnitine study in ID only because the constipation link and carnitine deficiency in your daughter lab test.
In my experience different forms (l-carnitine/LAC) and different brands have different impact, so it is a matter of some trials to see what's best for a child. I ended up with using CarnitAll - as a part of mitochondrial dysfunction treatment and to prevent drug related deficiency. Some parents claim that rx l-carnitine version (Carnitor) effect is significantly better than any OTC supplement, but it's not available where I live.
Actually carnitine was recommended for my son long ago by a mainstream metabolic paediatrician (who otherwise dismissed his medical issues and neglected autism treatment) due to his borderline blood levels, so maybe you can get prescription grade carnitine for your daughter this way?
My current dose is indeed ~50mg/kg.
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ReplyDelete