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Tuesday 18 July 2017

Neurodiversity or the Truth?


This blog is about the science behind autism and does try to avoid political agendas, which may make it seem somewhat cold and unemotional. Thanks to the internet, there are plenty of places to go and read about other views on autism.
I was reading one of the few scientific blogs about autism recently and I was surprised how much time was spent attacking neurodiversity and in the end it detracts from the science part of the blog.
Political agendas, like “America first”, or “Brexit means Brexit” and indeed “Neurodiversity” usually start with some truth and then everything gets lost in gross over-simplification. The more we move away from getting our information from serious considered sources and move to catchy snippets of information, the more people there are that think they have the knowledge to form a considered opinion, but the less valid those opinions may be.
Neurodiversity sounds like a nice idea; people are all a little bit different. Anyone who went to a non-selective school will already know just how different people can be. By studying the gene expression of people with autism, schizophrenia and bipolar we know just how varied people are and that almost everyone has an element of one observational behavioral diagnosis or another.
Neurodiversity only gets a bad name when one group at the extreme, that is defined by the lack of empathy and understanding for others, starts to hijack the debate; just like some intelligent person with Asperger’s may want to talk endlessly about his pet subject.
Fortunately, science and scientists clearly pay little attention to neurodiversity and so in countries like China, Canada and the US autism is very much seen as a medical disorder in need of potential treatments;  that is why thousands of research papers have been published. However many people there are out there adamant that autism is just a difference, and does not need treating, has no effect whatsoever. Science is elitist rather than democratic, you have to prequalify to get a say.
Not all doctors are scientists and so clearly they do absorb some of the background autism chatter. You will find doctors who are adamant that autism will remain untreatable.
Politicians, who often associate more with agendas rather than values/truths, are of course a different matter and they do count because they determine where your tax money gets spent. So the uninformed public debate can often lead to poor decision making and allocation of resources.
The truth sometimes can be boring and sometimes even dangerous, and is unlikely to win you an election or a referendum, but in the long run the truth is usually the best strategy. So ideally you want a politician with genuine values, compensated for by a good PR team to generate those memorable sound  bites.
Many people writing about autism, even award winning authors, not surprisingly seem to have mild autism themselves and so while they may have strong opinions, they may lack the ability to take in new information that might cause them to modify their opinions. So while you might want to check your math homework with one of these people, best not to try and debate anything with them.
In spite of the wave of autism awareness, most vaguely neurotypical people have little interest in the subject and so rarely express an opinion. That seems pretty much the way it should be.
Everyone is entitled to their opinion. Some people with mild autism are happy the way they are, but many people with disabling autism need help. Some people with mild autism also chose to seek help. Some people do not seek help until it is too late.
If this blog has an agenda, it is to promote the better use of the scientific research that has already been published and to take more control over your own health, just how much more and who should decide the limits are debatable points.









28 comments:

  1. Hi everyone,

    Not necessarily ASD specific, but extremely interesting, and who knows, maybe it will turn out to be ASD related:

    https://medicalxpress.com/news/2017-07-agent-toxic-proteins-cognition-neurodegeneration.html

    AJ

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    1. That article sounds indeed as it could be ASD related. Leukemia is a condition connected both to immune system and calcium channels if I remember it right, so looking for treatments on that avenue should be worth the effort. I think Peter once mentioned bone marrow transplantation for some autism; another crazy idea that probably would be very effective (and used for leukemia).
      /Ling

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    2. Take a closer look at EMR. EMR is known to interfere, alter and change enzymes. EMR is also known to alter calcium channels. EMR is linked to Leukemia, ASD, ALS. Protect your kids!

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    3. Also if exposed during pregnancy can cause chromosome breaks.

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  2. It is a double edged sword for sure.

    More awareness of autism in promoting "neurodiverse" individuals as more human I think has been good for my children in school as it was not long ago that children in these situations were treated far less tolerantly (at least here where I live in the USA). On the other hand, if autism is just "OK" and not even seen as a debilitating disorder, then there is less of an initiative by the public to "fix" or "cure" it like you had with the eradication of polio.

    After all, who is going to donate money to fund autism research and which politicians are going to devote NIH resources to autism research if there is no sense of urgency? If autism just means "quirkiness" or even seen superficially as just a bunch of cognitive tradeoffs, well it might help my children now in terms of how people treat them in school, but it will do them no favors when they graduate to the real world of the USA where adults only care about other adults when those adults can do something productive for them. For those not economically productive, our increasingly amoral populace could care less if you go off and die from an opioid overdose while at the same time scores of politicians keep talking about the "need to fix the opioid crisis" when privately they feel opioids are just culling the herd. I wonder how these people feel about anyone with intellectual disabilities if they think people who are down on their luck are expendable. I suppose those with ID are literally disposable according to this train of thought.

    So, there should be even more of an urgency than ever at treating autism in a serious way because once the genetic screening test comes along for autism, enough people in the USA will say that if you don't abort a baby with autism, then you deserve no sympathy for having it and that it is wasteful to spend taxpayer dollars on further autism research when you can just abort the problem out of existence at a much cheaper cost.

    So this is a race against time as I see things because killing people based on their genes is literally "genocide" and similar arguments in western nations from the turn of the 20th century seem to be repeating itself again as this kind of talk is becoming more and more common.

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  3. Roger, many people find the media coverage of autism to be annoying.

    We have to remember that in rich countries the lives of young people today with autism are very much better than they used to be.

    Fully verbal people with very mild autism, who used to be bullied in mainstream schools, now go to their own special schools. These intelligent young people may now have a one sided view of what autism is, and indeed what typical is, but they avoided a miserable adolescence and should be able to get a job. The downside is that some of these people now promote views that will drive you crazy.

    People with severe autism are no longer sent to live in institutions and many receive therapy of one kind or another.

    In poorer countries, where most people live, very little has changed. Autism means severe autism and life can be grim. They do not have special schools for fully verbal people with very mild autism.

    The preamble part of many scientific papers on autism often portrays autism as serious life-changing disease, which would drive people from ASAN crazy.

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  4. Here is some interesting research showing something new I have not seen before.

    Press Release:

    https://www.sciencedaily.com/releases/2017/07/170718084537.htm

    Paper:

    https://infoscience.epfl.ch/record/228269

    In effect, they found that diazepam (Valium) in low doses would help boost mitochondrial function in the major reward area of the brain (nucleus accumbens) indirectly via D1 receptor agonism from dopamine release in the ventral tegmental area. In other words, low-dose diazepam increases dopamine output the the nucleus accumbens which causes mitochondria to increase their metabolic activity.

    I recently read some other research I cannot find at the moment specifically on autism where boosting VTA->NA activity in a particular circuit improved social interest in an autism mouse model.

    All in all, this research may also indirectly suggest a mechanism in how treating neuronal mitochondrial deficiencies directly leads to specific behavioral improvements. This research also should bring backprevious discussions on this blog about low-dose clonazepam (another benzodiazepine) and its possible mechanisms of action in improving autism symptoms.

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    1. Tyler, yesterday my son got up at 3 in the morning and didn´t go back to sleep.He started with his OCD,knocking on all the doors because he wanted to raise the whole family.I didn´t know what to give him, nothing could calm him down,he dangerously started to lose his limits, challenging and redoubling the bet. When I catched him in the bathroom with his hands in the soup with the intention to empty it on the floor I asked him: what are you doing?He answeared me:¨I am going to wash my hands¨,becoming distracted while he opened the sink faucet.He never goes to wash his hands unless I tell him to do it.But that was only the begining.So,I dared to give him low dose diazepam, 1 mg, with his usual dose of valproate.All was better after that.Do you think that I could start to add it at bedtime? What happens with dopamine at this dose?Valentina

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    2. Very interesting. In general, I think heavy drugs for kids are bad unless you can prove that they help developmentally in the long-term, especially broadly acting drugs that are hard to predict what they are going to do in humans until many years down the road when it is too late. Addictive and tolerance building drugs are also in general bad (many if not most GABAergics), but as Peter has pointed out multiple times, sometimes doses low enough not to build a tolerance can still have remarkable effects. Also, sometimes a low-dose paradoxically causes bad as opposed to neutral effects while a higher dose makes things better. The simple facts are that even if we try and be as science based as possible in making good decisions for our kids, there is no consensus on what medications/treatments are best for autism. We all know that, so in this case if you had success with low-dose diazepam, then stick with that. I only posted this research because I find that research which is contrarian to my general views to be interesting and worthy of discussing if only to better understand the approaches others are taking in trying to find some useful answers.

      And with respect to paradoxical outcomes from a particular dosage of some supplement/drug, my son is doing great on Agmatine Sulphate now that I bumped the amount up the dosage quite a bit in lieu of recent research on the matter. On days he is not using it, his speech and cognition are shall we say different. There seemed to be an adjustment period the first couple of days with some agitation, but even after missing a few days, he has no recurrent agitations from using it again. Most people who use Agmatine Sulphate for other reasons suggest it is best to cycle it for 3 days on and one day off, but I don't know if cycling matters or not yet. What I do know is that it seems to have an acute cognitive boosting effect in a major way that goes away the next day if not resupplemented. The initial agitation I attribute to be most likely some immune reaction as Agmatine Sulphate impacts the opioid system and the opioid system is intimately tied to the immune system (this is just my best wild guess).

      The dose I give my son is a full teaspoon which comes out to 2.25 grams in a single dose in the morning which comes out to be 22.2mg/kg which is about the human scaled version of the rat valproate induced autism study that recently showed significant benefits from Agmatine Sulphate at that dose when you factor in intravenous versus oral administration.

      Agamatine seems to do a lot of things in the many papers I have read on the subject, but even though it is an NMDA antagonist which seems to help with some autisms, I think its main benefits are with regards to dopamine regulation indirectly via opioid normalization. In a genetics paper just this week on autism, it was found de novo mutations seem to have the biggest impact in the amygdala, striatum, and cerebellum. Both the amygdala and striatum are super rich with opioid receptors so even though modulating opioid signaling has been a research area with autism for many decades, I have not seen much new research lately (perhaps the topic has been beaten to death already). Nevertheless, I can say at this time the Agmatine Sulphate is no fluke. I will see how things go once he goes back to school, just I wish Agmatine Sulphate had more permanent effects because it is not the greatest tasting stuff (son won't do pills) and is not always easy to get down when you are in a hurry.

      So if I were you, I would at least try it out if you can because it has been a big success so far for my son at the paradoxically high dose while medium level doses seem to cause anxiety problems (or at least they did initially), with the caveat you will want to stick with it for at least a week before making a final judgement to keep using it or not.

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    3. Tyler,I will order Agmatine but will be able to get it in a couple of months.Now, will try low_dose diazepam at bedtime and see if the good effect is maintained.
      Valentina

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  5. Roger as per the genetic screening bit, if there is seen to be 33% chance of autism in a fetus, many parents are going to be privately pressured to abort the baby. My current understanding of the research has some recent studies putting genetics to environment at 1:1 while a few very recent studies put the ratios at 5:1 and even 9:1. It is obviously a very contentious topic. In the United States women who are poor whether they are married or not are routinely pressured by their families, friends, and even their husbands to abort their child just because they are poor. Using that reasoning Jesus himself would have been aborted if his mother lived in the United States. With that kind of awul mentality, it is naive to think the same kind of pressure will not be brought upon women whose fetuses are screened for autism and have a significant chance of developing autism, just as in Western Europe genetic screening has led to as high as 90% abortion rate for those with Down Syndrome.

    I am just saying we should all pay close attention to the law of unintended consequences when thinking about how these topics should be approached, though I am not sure whether we can do much one way or another as there is a commercial demand for prenatal autism screening by those people sympathetic to eugenics and unless there is a law banning abortion based on genetic screening that can be practically enforced, it doesn't matter what I or anyone else says. Even then several countries in the world have bans on aborting children based on gender, but these laws are mostly supercicial and therefore routinely ignored.

    As to your last point I agree. Categorizing people based upon a few gene variants is no different than categorizing people by skin color. Allowing the neurodiversity types to self-segregate themselves into a new class of personage is a slippery slope for everyone.

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  6. Roger, it was much better when mild autism was called Asperger's because then you can separate out what people's needs are. People with Asperger's have a substantial suicide risk for example. Now you get stories saying things like most mass killers have autism, when the truth is that they often have features of Asperger's/Schizophrenia/Bipolar.

    As I said in by post above, over-simplification just leads to misunderstanding and misinformation.

    We could now add mild Asperger's and the new phenomenon of self-diagnosed Asperger's.

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  7. Off topic but very useful resource here: http://www.findmecure.com/ClinicalTrials/Search?condition=autism&openStudiesOnly=true

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  8. Hi everyone,

    A couple of new papers revolving around dendrites that may be of interest:

    http://www.nature.com/articles/s41598-017-06121-2

    "PLD1 promotes dendritic spine development by inhibiting ADAM10-mediated N-cadherin cleavage

    Synapses are the basic units of information transmission, processing and integration in the nervous system. Dysfunction of the synaptic development has been recognized as one of the main reasons for mental dementia and psychiatric diseases such as Alzheimer’s disease and autism. However, the underlying mechanisms of the synapse formation are far from clear. Here we report that phospholipase D1 (PLD1) promotes the development of dendritic spines in hippocampal neurons. We found that overexpressing PLD1 increases both the density and the area of dendritic spines. On the contrary, loss of function of PLD1, including overexpression of the catalytically-inactive PLD1 (PLD1ci) or knocking down PLD1 by siRNAs, leads to reduction in the spine density and the spine area. Moreover, we found that PLD1 promotes the dendritic spine development via regulating the membrane level of N-cadherin. Further studies showed that the regulation of surface N-cadherin by PLD1 is related with the cleavage of N-cadherin by a member of the disintegrin and metalloprotease family-ADAM10. Taking together, our results indicate a positive role of PLD1 in synaptogenesis by inhibiting the ADAM10 mediated N-cadherin cleavage and provide new therapeutic clues for some neurological diseases."

    AND

    http://www.nature.com/articles/s41598-017-06140-z

    "The Wnt receptor Ryk is a negative regulator of mammalian dendrite morphogenesis

    The unique dendritic architecture of a given neuronal subtype determines its synaptic connectivity and ability to integrate into functional neuronal networks. It is now clear that abnormal dendritic structure is associated with neuropsychiatric and neurodegenerative disorders. Currently, however, the nature of the extrinsic factors that limit dendritic growth and branching within predetermined boundaries in the mammalian brain is poorly understood. Here we identify the Wnt receptor Ryk as a novel negative regulator of dendritic arborisation. We demonstrate that loss of Ryk in mouse hippocampal and cortical neurons promotes excessive dendrite growth and branching in vitro. Conversely, overexpression of wildtype Ryk restricts these processes, confirming that Ryk acts to restrain dendrite arborisation. Furthermore, we identify a hitherto uncharacterized membrane proximal subdomain crucial for Ryk-mediated suppression of dendrite morphogenesis, suggesting that it may act through a novel signalling pathway to constrain dendrite complexity. We also demonstrate that Ryk performs a similar function in vivo as Ryk haploinsufficient postnatal animals exhibit excessive dendrite growth and branching in layer 2/3 pyramidal neurons of the somatosensory cortex. These findings reveal an essential role for Ryk in regulating dendrite complexity and raise the intriguing possibility that it may influence neural plasticity by modifying dendritic structure."

    Please share any insights you may draw from these, as will I when I get the opportunity to delve further into them.

    AJ

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    1. AJ, I think modifying dendritic spines will become a therapy for autism and bipolar. An enzyme called GSK-3 β inhibits Wnt and some new drugs target GSK-3 β.

      There is a good article here:-

      http://www.sciencemag.org/news/2016/10/new-clues-how-lithium-soothes-bipolar-brain-may-shed-light-other-mental-illnesses

      It looks like fine tuning dendritic spines with either a Wnt activator or inhibitor, may become a viable therapy, even in older people.

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    2. Hi Peter,

      Thanks for the additional information! Good article indeed.

      Peter, as the article speaks to Lithium as a GSK3 Beta inhibitor that helped in mice (not a perfect proxy for humans), I would really appreciate any insights you may have on the impact of Lithium versus other GSK3 Beta inhibitors

      One of my favourite go to sites is "Self-Hacked" and it lists Lithium as well as Luteolin and Apigenin amongst others as potent GSK3 Beta inhibitors:

      https://selfhacked.com/blog/gsk3b-inhibition-potent-pathway-improve-brain-function-mood/

      I have Luteolin in my treatment protocol but not Lithium (orotate). I had considered Lithium but haven't tried it yet. Any thoughts on Lithium, especially if I'm already using Luteolin?

      Your insights are always much appreciated!

      AJ



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    3. AJ, I think that most people with autism likely have too much Wnt signalling, rather than too little, this is why they have too many dendritic spines rather than too few. So I think they will need a Wnt inhibitor. This could be a GSK Beta activator.

      I think the people with autism who would benefit from a GSK3 inhibitor are the ones born with small heads/bodies. This is a minority of autism.

      Potent Wnt inhibitors will have other effects, one obvious one will be changing hair color to gray, at least in some people. So if a proposed Wnt inhibitor has this effect, then it likely really does work.

      In Toronto they are trialing Tideglusib, a potent GSK3 Beta inhibitor, in autism. I think they should be trialing it in adults with bipolar.

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    4. Hi Peter,

      Thanks very much! I'm using Luteolin to reduce the inflammatory effects of Microglia, but it seems like it helps in that arena but then may be problematic in another (i.e. GSK3 inhibition).

      My daughter is definitely tall, so I'll have to look for an inhibitor of Wnt signaling. A quick check seems to indicate berberine, but it is so bitter that I can't use it until my daughter can take capsules.

      ASD is such a challenge - something that appears to be helpful in one area (Microglia) can be problematic in another (GSK3 inhibition).

      Always appreciate your insights Peter!

      AJ

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    5. AJ, luteolin and some other flavonoids do inhibit some cyp450 enzymes - i think it is cyp3a4 for luteolin. So perhaps if you are using other things - supplements or drugs that are metabolized through same enzyme pathway - that pathway is overwhelmed. So many variables!

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    6. What is wrong with inhibiting GSK-3? It is actually good for activating neurogenesis and reducing psychosis, reducing the buildup of Amyloid-β in Alzheimer's, increasing glucose tolerance in type-II diabetes.

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    7. Some people may need more GSK3 and others may need less. Both activators and inhibitors are being developed, but it has very many effects so a particular person may experience both good and bad effects. Inhibiting GSK3 will activate Wnt. If you have too much Wnt activity that would not be a good idea.

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  9. In an earlier post you briefly discussed Fisetin:

    https://epiphanyasd.blogspot.com/2016/12/refining-antioxidant-ros-rns-therapy-in.html

    Well a recent paper released in the last week or so I just finished reading follows up for Fisetin in a study on an Alzheimer's disease mouse model and comes up with some interesting conclusions that may be very relevant to autism.

    Press Release:

    https://www.sciencedaily.com/releases/2017/07/170710160954.htm

    Paper:

    https://academic.oup.com/biomedgerontology/article-abstract/doi/10.1093/gerona/glx104/3860587/Fisetin-Reduces-the-Impact-of-Aging-on-Behavior?redirectedFrom=fulltext

    The main finding (there are others in this paper though) I feel is relevant to autism is that fisetin seems to help elevate the levels of DHA in the brain. DHA in addition to Vitamin D in previous research has suggested to be very important in regulating the levels of peripheral serotonin relative to CNS serotonin. Simply taking DHA supplements is not necessarily going to increase brain DHA as like most things in the brain, levels of this fatty acid are highly regulated.

    There are other findings in this paper that more or less integrate well with a whole host of topics covered on this blog, even though fisetin supplementation is not a new idea with autism (from my cursory searches), especially since it was mentioned briefly in the aforementioned post.

    I would not expect fisetin to be a miracle supplement on its own, but it could be one of those substances that can add cumulative improvements for its antioxidant and DHA sparing capabilities that seem to be important factors to address in many autisms.

    By any chance has anyone ever supplemented fisetin before?

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    1. Tyler, I have not tried Fisetin, but many related flavonoids do seem to be helpful. In addition to the usual ones Quercetin, Luteolin etc, there is also Myricetin. This is why fruits and berries are good for you. Some flavonoids are poorly absorbed. I would be interested to hear from people trying Fisetin or Myricetin. I could not see any reports on the internet.

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  10. Peter, is Myricetin the same as DHM, di-hydromyricetin? It is widely advertised online as a hangover preventative. I found a study on DHM which mentioned that it acted on GABA receptors, but the details of it got a bit dense for me.

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    1. They are different substances, but both are flavonoids.

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  11. Hello Peter,

    Sidestepping the issue of neurodiversity, neurotribes, neurotypicals versus atypicals and who needs treatment and of what kind and magnitude I just wanted to share something. A few days back, I was reading an online book put up for free on the son rise program site (eyebrows raised?). Well, I am a big fan and unapologetic about it. A few of their book were amongst my first reads and really made me comfortable about the diagnosis and I do try and incorporate some of their methods/attitudes in our lives. The one I was reading online was about a five and a half year old boy (my son's age) who came to the Kauffman s with severest retardation in all developmental spheres and how he miraculously bloomed over a period of one and a half year. Amazingly, the narration seemed like a condensed version of my sonz developmental course.. my sons three years like robertitos one and a half years except my sons better in some areas but lagging in speech. Even some of the major and surreal events mirrored the ones we encountered. I a m sure many parents with kids who are a bit different have experienced moments of deep awe. And then two days back I was in our bed reading and my son smooched me properly (he cannot do it and makes a ba sound while kissing) on the forehead and then cheek. He could not do it again. Yesterday, at my sons therapy center, it seemed I had become an autism magnet. The best part was that while music was being played and the kids were dancing, one nine year old, most severely autistic boy with intellectual disabilities left the group, faced me and kept moving his feet in sort of dance all the time smiling, gazing deeply into my eyes. This went on for almost ten minutes and even the special educators smiled at this 'contact'. I of course kept on smiling too, feeling graced by the childs acknowledgement of my presence.

    What I mean to say is that in trying to design a better life for those we love, sometimes we fail to relate to the wholeness of the other, the dignity that has to be maintained and not violated. This also holds true for those who might be physically infirm, obese, ailing or old and 'demented'. Their is sancity to life.

    To Peter...sorry but I in no way imply autistics do not need treatment based on science.

    But to the autistics who made my day....Amazing grace!

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  12. Its fun being Aspie and people don't have a clue because you were never diagnosed. People have think you are different and cannot figure it out. The reverse could be said about Neurotypicals who lack the ability to see the patterns, who lack the ability to see the way the others with a different mind see the world. If you only knew the beauty of it and how neurotypical minds take it away from universal consciousness.

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  13. Here are some links you may be interested in reading:

    https://pragmaticskepticism.wordpress.com/2016/10/27/an-open-letter-to-the-neurodiversity-movement/

    https://pragmaticskepticism.wordpress.com/2016/03/24/major-flaws-within-the-neurodiversity-movement/

    https://pragmaticskepticism.wordpress.com/2016/11/23/a-reply-to-the-user-and-neurodiversity-advocate-autistinquisitor/

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