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Thursday, 4 January 2018

The Autism PolyPill 5 years on from December 2012

2nd WOW!

Still autistic, but less so, and no longer cognitively challenged.

It is exactly five years since Monty, now aged 14 started his Polypill therapy. At first it was just bumetanide, but shortly thereafter NAC and atorvastatin were added, more followed later.  All without any side effects.
I received Monty’s end of term school report just before Christmas and it bears little resemblance to what he received back in 2012. Now it does not look like the report of someone who is cognitively challenged. Almost all the grades are As; these are his best ever results and unlike 5 years ago, these are the same tests as taken by his NT peers, not an easy version. 
At the beginning of this first year in high school, there was a view that Monty should not be there, that he would fail to cope and later have to leave; he has proved otherwise.  None of this was malicious; it was just that the head of the high school used to teach in the junior school and has known Monty since he was four years old. Back then, and until he was nine years old, he was seriously challenged, academically. The post-Polypill Monty came as a big surprise, he is still autistic, but now academically functional.  He is now never disruptive and behaves like an attentive model student, just one that does not talk much.
Monty’s assistant recently asked me why, since some doctors do read this blog and apply it, don’t more doctors now treat their kids with autism? She mentioned a top local neurosurgeon who has twins with severe autism; why isn’t he treating his own kids? If you can do it, why can’t he? My answer was that a neurosurgeon is not a neuroscientist.   His job is quite primitive; he drills holes in people’s skulls and pokes around for visible defects in the brain. Treating autism is about tweaking tiny things like ion channels that you cannot even see. Being a neurosurgeon does not really help much, unless you read the neuroscience literature, which he likely does not.  

Wow Moments
I do like “Wow moments”. They do not come very often, the last one was four years ago when I first saw a little yellow pill (Verapamil) make an extended episode of self-injury, melt away in front of my eyes. That was like winning the Lottery and this therapy continues to have the same effect.
A “Wow moment” occurred in late December when I opened the end of term report, of Monty’s NT big brother, who attends the same school.  Monty’s grades are better. Yes, Monty is in year 7 and big brother is in year 13, his final year of school. You should not compare one sibling with another sibling, but nobody would have dreamt that a boy with classic autism would ever outshine his intelligent NT brother academically, under any circumstances. I think that deserves a “Wow”. Even big brother was impressed by little brother.
Nowadays an autism diagnosis usually is not associated with MR/ID; it is much more likely to be better described as a variant of Asperger’s. If you have Asperger’s there is no reason you should not aim for College/University. Unfortunately that is not Monty’s case, he has strictly defined autism (SDA), meaning more severe biological dysfunctions and his school reports from 5 years ago reflected that. He could not function academically; school was more for “socialization”.  People with SDA usually do not make it past the basics of school academically.  Where we live, autism = SDA and severe autism means something extremely challenging, so I find it very strange to read comments on the internet written by people claiming to have severe autism themselves.
One medical researcher recently asked me how effective is sodium benzoate (NaB) proving as a cognitive enhancer. All I could say was the current level of academic performance is shocking everyone. We had teachers thinking the assistants were boosting his test performance, so we all agreed to be super careful not to give help during tests. So now they are 100% his work, before I think it was 90% his work with some “hinting”.  I cannot say with certainty whether NaB helps or not. I stopped for a week over Christmas, and I concluded that there may well be a difference.
The extreme case of “hinting” is so-called facilitated communication, when the assistant ends up doing 90% of the work. The result is an illusion of what you would like to think the child is capable of, rather than reality. We do not need any of that.
There are also prompting methods like RPM, but at the end of the day what matters is what the child can eventually achieve entirely unaided. It does not matter if they type their work, or handwrite it.
Is the OAT3 inhibitor helping? For the last few weeks I have used coffee flavanols to boost the pharmacodynamics of bumetanide (by delaying its excretion). 
There are still plenty of ideas I have not yet implemented (RORα, PDE4 etc.) but the current PolyPill has delivered results far beyond my expectations. I do not think it is realistic to go from strictly defined autism (SDA) to entirely NT. The target I mentioned long ago was to go from SDA to something like Asperger’s. Monty is never going to be quite like his older brother, but after 5 years he now evidently has a typical level of IQ, and most importantly he can apply it at school and in daily life.
This Christmas Monty made his way through the self-scanning passport control at the airport and when randomly selected for the whole body scanning machine, he coped without incident.  Air travel is now a highlight of a trip and the more turbulence the better.
Now to the next five years.
The open question is whether Monty can obtain formal educational qualifications. In the English system there are externally assessed exams at age 16 (year 11) and at age 18 (year 13). Monty’s class group are two years his junior, so he will be 18 at the year 11 assessment. Years ago our piano teacher, who only teaches people with special needs, was pretty blunt about the fact that none of her kids leave school with formal qualifications, except sometimes in music. 
The situation varies greatly depending on where you live.  In the US things are very different and if you have an IEP (Individualized Education Program) and attend high school, you automatically seem to “graduate” high school with some kind of diploma. Many people with an IEP in the US do not have severe learning disabilities and they graduate with the standard diploma.

Monty has never had an IEP because he does not go to a school that offers them. In effect he has had a very customized education program for more than a decade, just it was run from home.




30 comments:

  1. Hi Peter, Happy New Year to you, family and readers.
    It's wonderful that Monty is not cognitively challenged anymore.
    I suppose you have stumbled upon this article:
    "Parents giving unproven IQ-boosting drugs to kids with Down's"
    "Drugs like Prozac and bumetanide show early promise for boosting intelligence in mouse studies, but activists say we should value people for who they are"
    https://www.newscientist.com/.../mg23130864-100-pare.
    Peter, would you please have a look at this paper and tell me in brief what it says? I am not sure if I understood it well, just trying to see if this is relevant/significant to my case report.
    https://www.ncbi.nlm.nih.gov/pubmed/10485996
    Petra

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    1. Petra, Happy New Year.

      According to another paper on this same subject, "recent work has shown that re-induction of synaptic plasticity by chronic exposure to the serotonin reuptake inhibitor fluoxetine involves upregulation of BDNF and downregulation of KCC2".

      In other words Prozac should down-regulate the transporter that lets chloride out of neurons, so the neuron goes back to being immature as in a new born baby. This would seem to be opposite of what you want.

      However if you believe that Bumetanide helps Down Syndrome (DS) you would think that Prozac should make cognition worse in DS. Apparently Prozac helps DS and in the US hundreds of kids are taking it for cognition.

      Timing of therapies for Down syndrome: the sooner, the better
      https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4594009/

      Parents Turn to Prozac to Treat Down Syndrome
      https://www.technologyreview.com/s/545191/parents-turn-to-prozac-to-treat-down-syndrome/#comments

      Science does sometimes get things the wrong way around, so the real effect is the opposite of what you expected.

      So I think it is something to look further into, but Prozac does have side effects. Many people with autism do take low doses for anxiety.

      Delete
    2. Down Syndrome involves excessive cortical interneurons in the prefrontal cortex, but for whatever reason some research points to these interneurons sometimes having an NKCC1/KCC2 imbalance in favor of NKCC1. I know you already know this.

      So in DS you have both an excess of interneurons as well as them working in reverse at the same time. So if you improve the NKCC1/KCC2 ratio with Bumetanide you are going to have excessive inhibition, so perhaps this is where Prozac can help with regards to BDNF selectively decreasing inhibition in select populations of interneurons.

      Then again SSRI's do so many different things which is why they should usually be avoided in children, but in this case with DS they may help in a paradoxical way with regards to this push/pull mechanism utilizing Prozac and Bumatenide.

      Delete
    3. In our case Prozac (20mg/ not every day) with Bumetanide seems a good combination.
      Prozac doesn't help much with anxiety. It really helps with OCD like symptoms, "learned helplessness", for instance, arising from previous traumatic events/failures.
      I found this article about the mechanism of the contribution to memory by immature neurons in the adult dentate gyrus :https://brage.bibsys.no/xmlui/handle/11250/276690
      ...This finding supports the idea that immature neurons in
      the dentate gyrus play a role in flexible adaption of their behavior in response to
      changes in the environment, by suppressing previously learned behavior... These immature
      neurons may contribute to flexible behavioral adaptation in response to alterations in
      the environment which render previously learned behavior obsolete. We propose that
      immature neurons can exercise this contribution by virtue of their distinct firing
      properties compared to mature neurons....

      Petra

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  2. Hi Peter, happy year! Iam glad that Monty is getting better and better, specially academically. We are doing great with bumetanide. We are off valproate since we started.Regarding the allergy,I got levocetrizine and was giving 2.5 mg each day.Today I was able to get verapamil.It comes in two forms,one that brings 80 mg per tablet,and another one of prolongued release of 120 mg. Which of the two would be better and what dose? Valentina

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    1. Valentina, I use immediate release 40mg tablets, sometimes cut in half. The 120mg tablet is too big. I would use the 80mg tablet cut into 4. First check it is tolerated, then check if it has any benefit. The benefit can be varied, for Monty it reduces anxiety and halts self injury which seems to come from allergy. In some people it solves their GI problems.

      So try 20mg on the first day to check it is tolerated.

      Verapamil has a half-life of about 3 hours. I give it twice a day in the allergy season, at 7am and 1pm.

      Delete
  3. Hi, I tried to comment yesterday and my comment did not go through. I apologize if I tried to post multiple times - I am not trying to spam / overwhelm your blog. I am just a desperate mother who did not realize that your comment moderation is on. I have an 8 yr old non-verbal son and we live in California. I am looking for some guidance from you. I know every child is different so will not ask if your son was ever verbal or not etc. But we did LP and my son did not have high serotonin levels and his thyroid levels were normal. However, he does have abnormal EEG and he has chronic urticaria (so potential mast cell issue). Will your poly pill work for my son given that he does not have high serotonin or abnormal thyroid ? Again I am trying to learn as much as I can but would appreciate your response in the meantime.

    Thanks !

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    1. Given your son has chronic urticaria, the mast cell therapies in this blog should help. In addition to the Verapamil in the Polypill, there are several others, many of which are well known, different ones work for different people:-

      Quercetin (OTC)
      Histidine (OTC)
      Biogaia probiotic (OTC)
      Curcumin (OTC)
      Cromolyn Sodium
      All H1 antihistamines (some OTC and some need prescription), the older ones are more potent than the new non-sedating ones

      In the Polypill, Bumetanide is the main cognitive enhancing drug and you likely have about 50% chance of it working, but you have to solve the mast cell issue first.

      NAC works very well for most people.

      So to answer your question, it is well worth trying what is in my Poypill, but if you do not resolve the mast cell problems any effect may be not be evident. Many people have found this and when the allergy comes back the Polypill "stops working". In effect the inflammatory process caused by the allergy makes autism much worse.

      Many people find they need multiple therapies for mast cells and each one stops working after a period, so you need to vary them.

      Delete
  4. This is really something to celebrate Peter. You should be extremely proud of both yourself and Monty. Wow WOW! It is an astonishing achievement that shines its hopeful light for all of us in the dark.
    Happy new year to all of you!
    /Ling

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  5. Peter, congratulations! You have made such a difference in Monty's life and countless others. I know you mentioned further exploration potentially on RORα, PDE4, etc. but was wondering if you are looking into other things on the horizon of which there will be future blog posts? You may not want to divulge but always interesting to see a window into what else you are looking at?

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    1. My posts are not planned far in advance, they tend to be prompted by comments and recently published research. There will be a post about the effect of certain bacteria, which seems to be a popular subject. There will also be a post on Glass syndrome.

      Delete
  6. Hi Peter,

    Just a quick note to say congratulations to you, Monty, and your entire family! Through your sheer drive, determination, and knowledge, you have achieved what most clinicians would have said is impossible.

    And please know that through your willingness to share your knowledge and by creating this forum, you have helped many others (including me and my daughter).

    AJ

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    1. AJ, my hope is that more people investigate their specific type of autism and tailor their own Polypill to match it. Much is possible and it is helpful to read about other people's experiences treating their case of autism, even when it is a very different type.

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  7. Hi Peter,
    Congratulations and it gives us all hope. Your patience and help on this blog is appreciated.
    I have just started back on bumex for a week for my son, seeing good things.
    Thanks
    BK

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  8. Peter, have you ever looked into any of all those machine interventions that Tyler seems to be the expert of? (TMS, light emitting things... uhm). There is a lot of people claiming good results and I do like the idea of interventions that don't "interact medically" (like also raising histamines)
    Why or why not?

    /Ling

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    1. You can probably find clinics that will do rTMS for depression on an adult as it is becoming more common, but other than in the research space it may be challenging to find someone to do rTMS on a young child with autism.

      As for tDCS and infrared light from LEDs they can easily be done with do it yourself (DIY) methods that people have been messing around with for decades, though more of the formal research supporting their use has only come around recently.

      All three technologies unfortunately are only suitable for cortical, and especially lateral cortical stimuLatin as well as lateral cerebellum and brain stem stimulation and much of autisms issues seem to be more subcortical than cortical. For example, the nuclei of the basal ganglia system seem to be deeply part of autism symptoms and they are too deep in the brain to be influenced directly by stimulating the lateral puts of the brain, though for diseases like Alzheimers researchers have been successful at stimulating subcortical structures like the hippocampus indirectly via stimulting the parietal cortex which has extensive connections to the hippocampus. The dorsolateral prefrontal cortex is extensively interconnected with just about everything in the brain so it has been a popular area of stimulation for tDCS and rTMS for autism research as well as just about everything else concerning humans and the brain in the hopes the right kind of stimulation will modulate activity indirectly in subcortical areas.

      Delete
    2. I'm with you Ling - these therapies are very appealing to me. For example, all of the praises being heaped on bumetamide use, is very frustrating for a parent if their kid has sulfonamide allergy. I'm investigating rTMS now for my son.

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    3. Tyler, by your earlier comments it just looks like you are targeting some of the same things that I do...
      I'd really appreciate if you'd briefly share your ideas and treatment choices on this, because you are a couple of years more into research than me.

      I remember that you like aspartic acid and are not much of a fan of l-serine or d-serine (why?). Also, you have mentioned spermine or if it was spermidine, which should have som similar effects to MgThreonate (and probably some not) - again, why and how much?

      Any thoughts on adding a glycine transporter type 1 inhibitor like sarcosine - yes/no?
      DAAO inhibitors - yes/no?

      Thanks also for the pterostilbene tip. I have some results to report in the near future!

      /Ling

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  9. Dear Peter, my Husband and I, wish to thank you. Our daughter has been using most of your polly pill for nearly two years along with early intervention, PECS and ABA. She is five, now verbal and like your son cognitively very smart. She can read fluently and play music, this in turn has improved her speech. Yes, she is still autistic with an improving receptive delay but her cognitive ability has improved. We believe like you, with your son, that our daughter, has the right to be very well educated. This year she will be attending a mainstream school with a full time aid. She was diagnosed at three to have very low functioning autism. Due to the daily taking of your polly pill, she can now read, write, count, interact, skateboard, surf, swim etc. Basically she has an enthusiastic love for life. I believe there is more improvement to come as she is maturing and self regulating her behaviour, initiating, asking for help and support. I do no live in a country (Australia) that believes that Autism can be treated. We took our Daughter to five Specialist and they all said not to expect her to talk, be toilet trained, understand or learn. Many people with Autism can be treated successfully with NAC, Broccoli Sprout Powder, Zyrtec and Bumetanide. I believe my Daughter was always smart we just needed to neutralise the side effects of her Autism. We cannot express our gratitude enough to you for your research. Thank you also, for everyones helpful comments. We wish all of your children happy and inclusive lives. Kind Regards Liz and Glen

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    1. Hi Liz and Glen am Australia myself just wondering where you are sourcing your bumetanide from if not from a doctor. What has zyrtec done to help your child kind regards Paul

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    2. Hi Paul, our Doctor explained to us that if we can get Bumetanide prescribed for our Daughter overseas, she could continue the script long term in Australia, as it would no longer be 'off label' use. This happens all the time for migrants who come to Australia on existing medications. We are anxiously awaiting French approval of Bumetanide for Autism. Zyrtec has really worked to control our daughters allergies during spring and autumn when the winds are strong. We live in the Coastal Bush, so pollens and mozzies can make our daughter miserable and the polly pill less effective. Peter talks much about the science of allergy and inflammation, for us it has been the key to making our daughter symptoms of Autism far less. I cannot talk for other parents and I am not a doctor but we have found great success in detoxing, feeding and protecting our daughter's brain. The poly pill is very mild compared to other medications and there are no highs and lows, of course we do have occasional monsoons, but our Daughter is only five and it is not always about her Autism. I am not an expert and these treatments have only worked for us. Broccoli Sprout Powder has helped so much, for our Daughter, really its quite phenomenal. We Buy the Super Sprouts Broccoli Sprout Powder, the Mediherb NAC, Brain Energy and P2 Detox. I make my daughter two frozen drinks a day. Both Super Sprout and Medi Herb are Australian companies which is great because often overseas products are no longer fresh by the time they get to Australia. You do need to buy from a retail outlet. Where I live, Go Vita discounts all products once a month for me as I buy the powders for my whole family. If I can help you further, please email me. Kind Regards Liz

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    3. Sorry Paul, Mexico, it goes under the name of Bumex Miccil Bumetanide 1 mg 20 Tabs.

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    4. Liz and Glen, I am glad your daughter is doing so well. I think by starting so young with both biological and behavioural interventions, you have fundamentally transformed her future.

      It was brave to give bumetanide to a three year old, most parents would not do this, but now you have a five year old in great shape. Time is on your side and in the next dozen years at school things can only continue to improve.

      Delete
  10. Thank you Peter, you gave us the confidence to do so because of your posts.

    Compared to the medication options our Paediatrician was giving us, bumetanide was safe and mild, as long as she had regular blood tests for her potassium levels and gave her a supplement. Our Daughter was trapped in her Autism, her brain was so inflamed. He only saw her as a behaviour to be managed, we felt her intellect needed to be protected.

    When I first spoke to my Family Doctor, of over ten years about bumetanide she told me she could not prescribe it because it was off prescribed use. I asked her what she would do if it was her daughter with autism, without pausing she told me she would give bumetanide to her daughter.

    My Husband and I took bumetanide, nac and broccoli sprout powder for a month, we felt great with no negative side effects. We started slowly with our Daughter, introducing one element at a time. She started to talk and calm down. She saw where we pointed, looked at us, she laughed and understood visuals and sign language. We could finally communicated with our daughter.

    Her speech therapists started to see incredible progress like never before. She apologised to us for not realising how smart our daughter was. We knew it was the poly pill but could say nothing, still cannot.

    Bumetanide, nac and broccoli sprout powder changed our family dynamics. Our four sons now have a sister who they love, not resent because of her additional needs, can show Family Guy, South Park and American Dad to, can teach to surf, skate and swim and buy junk food for. The universe is just as it should be, for her and them.

    I wish the medical profession could see that the crisis is with their ignorance. I realise their caution, but most do not even value early intervention and its associated therapies, which in Australia are wonderful.

    In Australia, doctors 'write our children off' at eighteen months for life. Research on appropriate biological intervention for all types of Autism is needed. Would doctors turn their backs on childhood cancer or diabetes? Look at the growing numbers looking at your posts Peter, the great majority must be desperate parents, just like we were.

    No pressure, but could You, Your fellow Scientists and Doctors please keep up the 'Good Fight’, and continue posting your knowledge and discoveries.

    Lastly, we might need help with longitude and latitude down the track.

    Thanks again, mate,

    Liz and Glen

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    1. Just a quick question once you started bumetanide how long was it before you noticed any changes and what were they and your getting the Bumetanide from Mexico is that through an online pharmacy or other means cheers Paul

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    2. Liz and Glen, I think by posting your experience treating your daughter you will encourage more parents to do the same.

      Even after Bumetanide is approved in Europe, I do not think doctors will rush to prescribe it, it will take years. Parents will have to demand it, which is not something people in Europe do; they just follow what their State-funded doctor says. People who pay for healthcare are much more demanding.

      I think your daughter will master longitude and latitude all by herself and her teachers will never appreciate just how far she has already progressed.

      Delete
  11. G'day Paul, Yes there are a few online pharmacies operating from Mexico.

    We introduced nac, broccoli sprout powder and bumetanide progressively one month apart to our daughter, accompanied by intensive early intervention everyday.

    We noticed the effects of the poly pill very rapidly. She saw a star in the night sky and pointed and said 'star' within a month of starting the nac. She also stopped rocking, running, vocalising and hitting the walls. Her brain was less inflamed.

    She became happy and joyful but in a calm way after the broccoli sprout powder very quickly. But it was the Bumetanide that made her 'see' and understand, after a month on it, she started to use phrases.

    She doesn't speak fluently like her peers but she does initiate conversation spontaneously with phrases and she requests with words, sign language and with and without PECS visuals.

    She sang all the nursery rhymes I had tried to teach her for years after a two month.

    Socially, she started to parallel play, moving closer and closer to other children. They responded and included her, we taught her to say 'Hi" and now her play is combination of parallel and interactive, a direct result of taking the bumetanide.
    At first her speech was mimicking but now she knows 400 words. She began to read street sign 'out of the blue'. She does not read phonically, all words are sight words but she understands their meaning and can read probably more fluently then she speaks. We taught her verbs first because we could show her what they did.

    We video modelled everything at first for her to see.

    She started to tell me after three months if she was sick, sad, happy which was a huge cognitive jump, she was developing a sense of self awareness. She started to ask for cuddles and kisses after six months, not just for basic needs like food and water. We were able to toilet train her with visuals after a year. It took three weeks in the toilet but after that she became much smarter.

    Now our daughter is not just a literal thinker she is a lateral thinker and a great problems solver because she observes everything. Yesterday, she told me that spiders, sharks and snakes bite and should not be touched. Another milestone because she does not fully understand danger.

    She can enjoy talking books with headphones and I believe follows the story because she laughs at Woody’s lines.

    She has become manipulative, which is a huge jump, she tried to steal her brothers Tim Tam yesterday with a cuddle and a kiss, she acted so coy.

    Educators have stopped telling us she is ‘low functioning’.

    Kind Regards
    Liz

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  12. Hi Peter, I realise that your your site is for scientific posts not personal stories, as I have answered Paul's question, please feel free to delete my posts.

    Thanks
    Liz

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    1. Liz, personal stories that support the use of scientific therapies are very helpful. Your answers are just what people are looking for. Thank you for commenting.

      Delete
  13. Still not through all of them, I really must say Peter that I appreciate the variety of your posts. Some are very detailed and complicated, some show the big picture and pathways, and some are just about how Monty is doing.
    The "easier" posts opens the door to understanding for me as a newbie (only one year into this) and make me interested and motivated enough to dig through the more complicated ones. And the ones on Monty make me relax and sometimes smile.

    My favourite ones are the educational posts that brings things together, and those explaining things in the synapse. If you don't mind, I would like to mention some wishes on topics that I'd like to read about.

    You have explained a lot on GABA, NMDA and a bit on mGlu5 receptors. I don't know if there is much to say about AMPArs and their subunits, or if they relate to autism at all. But I see that they are implicated in memory formation, and this is of course of interest to me.

    I don't know much about neurotransmittors at all, and I'd love a very basic lesson on which they are, what they do, how they relate, and how to recognize which ones are in action (behaviour? mood? blood tests? illnesses?). And of course how (if) they relate to what I've learned about ion channels and so on. Neurotransmittors have been discussed a lot in the comments, but I can't follow them since I don't know the basics.

    Also, it would be nice with a summary on what we know about the different subunits of all the receptors.

    I hope this triggers some inspiration. (-:

    /Ling

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