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Thursday, 13 October 2016

Multigenerational Epigenetic Change Stimulating Inflammatory Disease



Multigenerational transmission of nicotine-induced effects. The diagram illustrates the experimental design and findings of Rehan et al. [4]. Pregnant dams (F0 generation) are injected with nicotine or nicotine + rosiglitazone. The lungs and gonads of both male and female offspring (F1 generation) of nicotine-treated dams exhibit epigenetic changes, and the lungs show an asthma-like functional phenotype (blue nicotine-induced changes). These nicotine effects are not seen in the offspring of animals treated with nicotine + rosiglitazone. Offspring of F1 mated pairs (F2 generation) exhibit the same nicotine-induced changes to lung function as their parents, even though they were not exposed to drug.


Today’s post is again filling in some gaps in this blog to date.

A big question in autism is whether the incidence is increasing or not.  According to the now best-selling autism author Silberman, incidence is not increasing at all; it is just that diagnosis is much better than it was half a century ago.  So it is not an “autism epidemic”, rather a “diagnosis epidemic”.

I did not buy Siberman’s book and while I would like to believe he has accurately assessed the facts, in this case he really has not.

Psychiatrists have done none of us any favours by constantly changing the definition of autism and clinicians have never adequately collated data on those who match those criteria.

It does actually matter whether or not incidence of autism is increasing, because this would then stimulate research as to why.  In time this better understanding would lead to therapeutic avenues.

Being neither a professional researcher, nor a best-selling author, my level of evidence can be a little lower.  In earlier posts we saw incidence of ASD (autism, Asperger’s and PDD-NOS) is around one percent of both the child and adult population.  Many adults with Asperger’s and milder dysfunctions were never diagnosed as children, because they did not have speech delay or great cognitive difficulties.

The autism figures are always of low quality, but there is an opinion that underlying them is a real increase in severe autism, as well as the increased diagnosis of milder autism due to lowering of the diagnostic threshold.

The data I would like to see is the incidence of severe autism over the last few decades, but it does not exist.  All we have is anecdotes.

I remember asking my retired doctor mother how many patients had autism in her medical practice of about 10,000, where she saw all the children.  They did not have any and apparently until the Wakefield autism-MMR business nobody even talked about autism.

Hidden away in a group of 10,000 there “should be” about 100 with some degree of autism.  About 30 might have quite severe autism, many with MR/ID and epilepsy. 30 sounds a lot, but it is only one or two births a year.  People with severe autism live half as long as typical people, so you would not see many past middle age. I suppose it was easy to just diagnose mental retardation and then put the child into “care” when the parents could not cope.  

When a friend of mine from graduate school asked our alumni group of 200 how many had a child with autism there were six responses.  None were Asperger’s, all were strictly defined autism (SDA).

Some disease surprisingly does correlate with educational level.  I recently read that IBS/IBD is much more common among more educated people.

So my take is that hidden in all those poor quality statistics is a rise in the incidence of strictly defined autism (SDA).  Just as it is known that there has been a rise in inflammatory disease like asthma.

Asthma and COPD are really well researched and we know at least some of the reason why they have become more common.  I think the same general mechanism is behind the increase in SDA.

By understanding this mechanism you can then try and reverse it.  This is already being done in COPD research and some of the single gene autisms like Pitt Hopkins.

The mechanism is epigenetics, where you can modify when genes turn on, or turn off.  COPD is a severe disease because an environmental factor (normally smoking) has caused the body's oxidative stress response genes to be turned off.  Pitt Hopkins is caused by an insufficient expression of the TCF4 gene.  This was unlikely to have been caused by epigenetic changes, but could potentially be treated by using epigenetics to turn on the TCF4 gene.

Today’s post highlights pretty convincing research that shows how an environmental factor, smoking in this case, can cause heritable epigenetic changes.  It shows how a Grandparent smoking increases asthma incidence in the grandchildren.

Other than sending the message that smoking can affect the health of your future grandchildren, it becomes clear that many other environmental insults could also be heritable.  The accumulation of these insults over generations affects the incidence of certain diseases, particularly those complex ones often caused by multiple hits (cancer, autism etc.).
  
This makes me recall how it is theorized that epilepsy can develop as an acquired channelopathy.  We saw how the threshold for a person’s first seizure is quite high, but after the first seizure the threshold falls.  The proposed mechanism is called an acquired channelopathy.  This means that one of the many ion channels whose dysfunction is known to lead to epilepsy has been permanently disturbed.  The ion channel can now behave aberrantly with little provocation,

Ion channel diseases are classified as ‘acquired’ or ‘genetic’. Genetic ion channel disorders of the brain generally manifest as epilepsy, migraine, paroxysmal dyskinesia or episodic ataxia.

Acquired channelopathies can be caused by antibodies which target specific ion channels or by toxins which block voltage-gated ion channels. Altered transcription of ion channels may contribute to many acquired neurological ion channel disorders.

Mutations in genes which encode subunits of CNS sodium, potassium, calcium channels, GABAA and nicotinic receptors have been reported in association with various epilepsy syndromes.

While genetic (inherited) ion channel disorders may be the cause of most people’s epilepsy, it is suggested that acquired channelopathies are also involved.  Perhaps both are present?



 the “acquired channelopathy” hypothesis suggests that proepileptic channel characteristics develop during epilepsy.

In summary, cell type-specific information on epilepsy-related ion channel modifications can explain and support AED strategies. Precisely those inhibitory ion channels which appear to be effective AED targets in preclinical tests are the ones upregulated in DG GCs during TLE. These data indicate that cell-endogenous ion channel homeostasis mechanisms could be used as “channelacoid” archetypes in the search of antiepileptic strategies. In particular, the enhancement of static shunt via combined K/Cl/cation leak channel support appears to be a promising strategy.


The science, though complex, is still in its infancy.  You do wonder if acquired channelopathy cannot be caused by epigenetic changes to the genes encoding the ion channel.



Nicotine, your genes and those of your heirs

Finally, the subject of today’s post, the research showing the epigenetic effects of nicotine. In place of nicotine you could likely substitute other environment damage such as intense air pollution in cities like Beijing.  Another example below is lead pollution. 

 First the easier to read article:-


"Our results therefore indicate that the increased disease risk associated with smoking is partly caused by epigenetic changes. A better understanding of the molecular mechanism behind diseases and reduced body function might lead to improved drugs and therapies in the future," 


Now the more interesting study that shows how the effect of nicotine is passed down the generations to non-smokers.






Multigenerational transmission of nicotine-induced effects. The diagram illustrates the experimental design and findings of Rehan et al. [4]. Pregnant dams (F0 generation) are injected with nicotine or nicotine + rosiglitazone. The lungs and gonads of both male and female offspring (F1 generation) of nicotine-treated dams exhibit epigenetic changes, and the lungs show an asthma-like functional phenotype (blue nicotine-induced changes). These nicotine effects are not seen in the offspring of animals treated with nicotine + rosiglitazone. Offspring of F1 mated pairs (F2 generation) exhibit the same nicotine-induced changes to lung function as their parents, even though they were not exposed to drug.

A recent preclinical study has shown that not only maternal smoking but also grandmaternal smoking is associated with elevated pediatric asthma risk. Using a well-established rat model of in utero nicotine exposure, Rehan et al. have now demonstrated multigenerational effects of nicotine that could explain this 'grandmother effect'. F1 offspring of nicotine-treated pregnant rats exhibited asthma-like changes to lung function and associated epigenetic changes to DNA and histones in both lungs and gonads. These alterations were blocked by co-administration of the peroxisome proliferator-activated receptor-γ agonist, rosiglitazone, implicating downregulation of this receptor in the nicotine effects. F2 offspring of F1 mated animals exhibited similar changes in lung function to that of their parents, even though they had never been exposed to nicotine. Thus epigenetic mechanisms appear to underlie the multigenerational transmission of a nicotine-induced asthma-like phenotype. These findings emphasize the need for more effective smoking cessation strategies during pregnancy, and cast further doubt on the safety of using nicotine replacement therapy to reduce tobacco use in pregnant women.


More on epigenetic changes related to heart disease.





Finally the effect down the generations of lead, a known neurotoxin.



We report that the DNA methylation profile of a child’s neonatal whole blood can be significantly influenced by his or her mother’s neonatal blood lead levels (BLL). We recruited 35 mother-infant pairs in Detroit and measured the whole blood lead (Pb) levels and DNA methylation levels at over 450,000 loci from current blood and neonatal blood from both the mother and the child. We found that mothers with high neonatal BLL correlate with altered DNA methylation at 564 loci in their children’s neonatal blood. Our results suggest that Pb exposure during pregnancy affects the DNA methylation status of the fetal germ cells, which leads to altered DNA methylation in grandchildren’s neonatal dried blood spots. This is the first demonstration that an environmental exposure in pregnant mothers can have an epigenetic effect on the DNA methylation pattern in the grandchildren.



Conclusion

As regards autism, heritable epigenetic changes could well explain the increase in strictly defined autism (SDA) that cannot be explained away in terms of widening diagnostic criteria and awareness.

With respect to many diseases it is hardly surprising that they are becoming more prevalent if we accumulate the environmental insults experienced by our ancestors, via heritable epigenetic changes.  Where this will lead in future generations?

There are further studies looking at the role of PPAR gamma agonists (the rosiglitazone given to protect the mouse from epigenetic change) and HDAC inhibitors, which together can do very clever things regarding epigenetics.

You may recall the broccoli sprout extract being given by John Hopkins researchers to protect Beijing residents from the effects of severe air pollution.  The sulforaphane produced is an HDAC inhibitor.  

The mouse studies showed how to protect a mouse from epigenetic change occurring, what would be more interesting would be studies looking at reversing that change, once it has already occurred.

The only bad thing in the Mediterranean diet/lifestyle is smoking; just imagine how healthy the Greeks would be without smoking 2,000 cigarettes per adult per year, compared to 1,000 in the US.





26 comments:

  1. Peter, I concur with your graduate school observation. Of the 90 persons in section for my MBA program in the 90s, there is a large number of those parents with kids with autism (vs. not growing up with siblings who had autism). Also, in my community of 10K growing up there was one family whose child was disabled. Now there are many of the kids whose children are somewhere on the spectrum (and they are identifiable/observable). I am so glad that we have organizations and sites like yours to identify treatments.

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  2. If you think of all the things that have radically changed in the western lifestyle in just the past 50 years, which of course includes exposures to literally millions of different types of man made chemicals that never went under any serious scientific scrutiny as to their long-term safety, not to mention the idea of epigenetic inheritance is only around a couple decades old, you might ask why we don't have even more of a rise in neurological disorders than there are already in humans as well as wildlife and plants that have to live with the consequences of human planet domination.

    It is just fascinating how so much of what I was taught in high school science classes is now considered outdated or at the very least challenged. If I were a high school science teacher, I would not even know how to give an honest test of what is right or wrong because I could very well be instructing my students with erroneous information due to some new discovery being made a week before. I would probably have to teach science from an exclusively historical angle for it to make any sense and still be true.

    Nevertheless, scientific understanding keeps improving and some big news relevant to the work I have been doing the last several years just showed up which is also exciting for autism research studies for subjects that have problems staying still in a scanner:

    https://www.sciencedaily.com/releases/2016/10/161012183526.htm

    In effect, they were able to scan a fetus's brain and correct for motion artifacts. What this means is that these mathematical techniques likely (if they pan out in replications of the methods these researchers used) will allow non-sedated severe autistic subjects to have their brains scanned successfully.

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    1. Tyler, I agree that it is surprising how well humans cope with their environment, so well that we get upset when it goes very wrong 2 or 3% of the time.

      Epigenetic therapy is one way forward, but it is very slow because first it starts in mouse models of single gene autisms. Since many of the drugs are actually safe for humans, you do wonder why not go straight to humans, or at least ask for volunteers.

      A great deal is already known as in this paper.

      http://onlinelibrary.wiley.com/doi/10.1016/j.febslet.2011.05.007/pdf


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  3. Tyler,

    Endorsing your view about how everything that we were taught seems so questionable..there have been scientific advancements. Actually only those theories that have philosophical undertones, relativity, uncertainty seem to hold, that too not so much for the science part but the vague literally musings. Nothing seems to correlate to nothing and everyday we have pop researches coming out which seem to bunk an earlier hypothesis in a never-ending cycle of 'researcher proposes, researcher disposes'. So the era of theory is out and highly contextual best guesses is in and everybody has an opinion now. Whether that is a good or bad thing remains debatable. Although, its obviously a good thing if it improves quality of life for our species. Now what is quality of life is another open question.

    Well we were taught epigenetics. I remember I had linked possible deleterious epigenetic changes as a result of environmental toxins, to a projected decline in human reproductive potential in my ecology viva voce, much to the irritation of my ecology Prof.

    Tyler, you seem to have lot of knowledge about the human brain..it's development, structurally and functionally and where things might go wrong. Some latest rsearches on artificial intelligence have shown an almost eerie development of capacity to take independent and subjective decision, after the subjects were crammed up with information. Might research in that area hold promise for autism treatments?



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  4. Another far out there idea that I just had based on an avenue of research in autism that from my initial search seemed to not be explored:

    https://www.indiegogo.com/projects/rtx-the-pro-s-secret-to-staying-cool#/

    This is a device that I read about for the first time well over 5 years ago (if my memory serves me correctly) that cools the core body temperature of someone who puts their hand in this pressurized glove. Now, you may ask why not just put your hands in ice or jump in an ice bath. Well that will cool your body temporarily on its surface but then stimulate your body to start pumping out heat and restricting blood flow to the periphery (i.e. cooling your extremities but not your organs and your brain which your brain will fight hard to keep warm).

    Interestingly enough, I have thought about body temperature and autism for a long-time in terms of interventions but have not thought of a practical and safe way of doing achieving this because the last I heard of this device, it was in the experimental stage for a handful of American football teams. It appears now that this device should be available in a streamlined consumer version for $250 or so which is a lot more interesting than the $1000 dollar one marketed to college and professional sports teams.

    Now with respect to autism and body temperature, I dug up some stuff about a theory that Parkinson's disease might be partially caused by the physical overheating of brain cells, and one study specific to autism that suggested that oxytocin and serotonin in tandem help regulate body temperature via receptors on brown adipose tissue and that those with autism tend to have a harder time keeping themselves warm (i.e. they have cold affect). On the contrary, my son when he gets hyper gets rather warm and flush and I have never noticed him actually feeling cold to the touch, so this is where I have always had this suspicion that is cognitive ability may be dampened by a chronically high brain temperature.

    There is also of course the ongoing research exploring the fever effect in autism, but I suspect that is unrelated to core body temperature and has more to do with immune responses. In additon, there seem to be many types of sleep problems and since "cooling down" is an important natural process of phasing into sleep at night in a healthy individual, perhaps this could be an avenue of research not yet fully explored in autism.

    Last but not least, heating someone's core body temperature up temporarily is pretty easy (sit in a sauna or hot bath for a while and you heat up faster than you can sweat out the excess heat). I messed around with this on the basis of a small study that explored this idea as it relates to the "fever effect" with hot (not scalding hot of course) baths for my son and really never noticed anything profound, but seeing what happens when he is cooled down after getting hyper and beet red has not really been a possibility till now with this device because the only other way I know of doing this is to either swallow a bunch of small ice cubes (not possible with my son) or drink a whole bunch of very cold water in a short period of time (not going to work because your brain makes it harder to drink excess fluids as you ingest more which is not a great idea to do anyways if you force it, due to the threat of water poisoning).

    Just an idea for discussion. It would be a simple intervention to try (if you had one of these devices handy) and I am thinking about ordering one myself for this very purpose.

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    1. Interesting. I have always noticed that my grandson is so warm to touch.

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  5. Hi Peter,
    I am a smoker and I can feel there is something wrong with my nicotinic receptors and dopamine release because I can easily get addicted and have cravings for "rewarding" substances.
    My husband doesn't smoke, shows no such behaviours and so does my son.
    I have a feeling that my son's nicotinic receptors are also disturbed and I think his stimming behaviour as well as late onset sleep disorder has something to do with that. We also share in common very low LDL cholesterol levels which I believe is connected with a dysfunctional apolipoprotein process affecting nicotinic receptors and dopamine release. Of course I don't know which dysfunction comes in the first place.
    I have trialled nicotin patches and vitamin e and had behavioural changes I cannot evaluate extensively yet. I believe that as long as I can't combine them with something that helps low LDL I won't have a stable result.
    It's a project I am working on and doctors don't really help.

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  6. Peter, Do you think peanut butter would be as good as regular butter for short chain fatty acids production in the gut?

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    1. If you eat a diet high in fiber, the bacteria in the gut will cause it to be fermented to produce SCFAs.

      https://www.sciencedaily.com/releases/2015/09/150929070122.htm

      Butyric acid smells of rancid butter. It is contained in dairy products, particularly butter (not peanut butter).

      You need SCFAs, but too much can be bad. The best idea is probably to eat a diet rich in fiber.

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    2. Peter is right about all of this.

      The mix of prebiotic fiber I use is a 50/50 mixture of raw (uncooked) potator starch and barley flour plus inulin (a very well known prebiotic). One nice thing I have found accidentally is that if you just use potato starch in a smoothy or protein shake, it clumps together and has a pasty texture. If you just use barley flour in a protein shake or smoothy, then you get this grainy texture that can be offputting. But for whatever reason if you mix them both up in equal amounts in a separate container, you get this nice mix that plays nicely in liquid beverages. No genius involved in figuring this out, just something I noticed by accident. The inulin is sticky and tastes like sugar (because it is a long-chain sugar) and I put that in separately. So for a standard protein shake, I might do 4 tablespoons of the potato starch/barley flour mix and 2 scoops (10 grams) of the inulin.

      Potato starch is good for SCFA production, and barley flour has a polysaccharide in abundance called "beta-glucans" which has been shown to have many positive effects in gut health as well as glucose control and immune function.

      Ideally, SCFA's are produced in the large intestine, but some people seem to process prebiotic fiber (as well as excess fructose) earlier in the small intestine and it is thought that many of these SCFA's get drained via the portal vein straight to the liver which then converts the SCFA's to medium chain and long chain fatty acids for fat storage. That being said, the vast majority of people on western diets get only a small fraction of the prebiotic fiber they probably need to maintain optimal health with regards to the gut and immune system.

      Its a big area of research right now since obesity keeps rising worldwide and causing bigger and bigger economic and social problems with each year in western societies especially so don't take my opinions here too strongly and read about it yourself.

      The brands I use are Bob's Red Mill Potato Starch and Bob's Red Mill Barley Flour (I get it on Amazon) and then I get the Inulin from Swansons (but you can get it anywhere). Don't cook the potato starch or else it will break down the long-chain sugars and will be processed as carbs just like bread (one advantage of humans discovering fire and how to cook).

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    3. Thank you Tyler for this information but as you can understand, even if I found a way to do this, my son wouldn't eat it.
      Bete glucans can be obtained from some special crackers and he might eat them. I could also give him some soya lecithin as fiber source, which is good for liver.
      I can see that he has yeast on his scalp and it's smelly. I suspect that the ratio among SCFA's could be problematic. I did topical treatment with chamomile and drunk some with green tea. Is it easy to measure it?

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    4. My nephew, also with regressive Asperger's, showed GI problems from the beginning of his life, remaining unsolved.
      In my son's case things are not pesented as clear as my nephew's.
      Doctor's advised on high fiber and mumerous special diets with fruit, vegetables, legumes and all that healthy stuff but they didn't work.
      Then another doctor told her to forget about special diets, feed him on whatever other kids eat and use castor oil with tanilas laxatives.
      As I read tanilas (macrogol) has polyethylene glycol, a therapeutic agent which targets immunogenicity and antigenicity, affectinf B and T cells. It is also used for Parkinson's disease.
      Hardly ever does he show extreme GI problems after the therapy, which was stopped after a reasonable while.

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    5. Tyler - I for one appreciate the many informative comments you have left on this blog. I am wondering if you ever got around to posting your full treatment regimen, as was discussed awhile back I believe in response to Ali's suggestions about Bio Gaia. I have looked for it but perhaps missed it. I would be very interested to read what drugs/supplements/foods you believe are helpful.

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  7. I'd like to add my personal feeling, which is not far from the stereotypical depiction, that we Greeks maintain our extrovert temperament because we are in fact dopamine seekers and it would be interesting to know how the mediterranean diet adds to that "pathology".

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  8. Let me add these two links to the discussion,that were the first things I thought of when I saw this post.

    This blog post from Jill Escher about smoking in grandmothers,and epigenetic changes that can lead to autism.

    http://www.germlineexposures.org/blog/is-grandmaternal-smoking-the-primary-force-behind-the-autism-surge

    And this JAMA Network article that was linked the other day,on Paul Whitely's Facebook and Twitter feeds.

    http://jamanetwork.com/journals/jama/article-abstract/2553337

    Basically it says what I,and others,have been saying for years.That there very likely is an increase in autism and ADHD,but much of it looks like it can be traced to neurotoxic chemicals babies have been exposed to in the womb,and in the first year or so of life,that babies were not being exposed to decades ago.

    http://jamanetwork.com/journals/jama/article-abstract/2553337

    JAMA is putting a call out "for increased monitoring, assessment, and reduction of neurotoxic chemicals".

    As you have said before,up until maybe the 1980s or so,children with more severe autism were put away in institutions,where they did not live very long.My mother was one of the rare exceptions to this rule.

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    1. Interesting blog post about grandmaternal smoking. I will be sure to bring this discussion up with my mother in law this weekend. If you don't hear from me on this blog ever again, well then you will know why.

      On second thought, maybe I will wait for the formal research on this matter to come out before risking my marriage, kids, and maybe even my life (-:

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  9. My mother and her mother were bodily clean individuals..most Indian women are, including me!

    I am sure my son's autism came from my husband..what with him, an almost middle aged man with a Ph D watching endless reruns of 'Pirates of the Carribean'.

    My paternal grandmother did the hookah and chewed tobacco and betel nut, so did her mother and mother in-law. My husband's grandmothers from both sides did traditional versions of drugs and smoke and this has been going on since generations. And they had huge broods with no sign of neurological disorders in any.

    We cannot solve problems with the same level of thinking that we used to create them..quoting Einstein.

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  10. Hello Peter,

    Do you really think autism rates have increased..I do not know what to believe. Sometimes I feel that strict impositions of Western concepts of developmental milestones have lead to inclusion of many higher functioning kids whose disabilities, particularly in areas of language and socialization would not have become as limiting or conspicuous in societies where visual learning and physical engagements were more prevalent.

    Transition of society from that of silent doers to one of those ideating, opining and communicating more might suddenly bring out deficits in lot of individuals. The more severe ones, I feel were just not counted, shunned in western societies and absorbed in not very judgemental eastern ones.

    And coming to autism treatment on lines of cancer therapies, a discouraging study has shown that we are not winning the battle against cancer. Death rates have remain largely unchanged while incidences of many cancers have increased. Now, what would have been helpful here was an age wise measure of increase, as greater longevity could be one reason behind an observed rise in many diseases apart from better diagnosis.

    So it's all very confusing. More the things change, more they seem to remain the same.

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    1. Kritika, I originally thought what was happening was just a huge increase in people with very mild autism getting a diagnosis. There are also people who before had an MR/ID diagnosis who now have an autism one as well.

      There is no reliable data to prove any point of view, but it looks to me that there has been a rise in the severe kind of autism that would have been diagnosed as autism even 30 years ago. This does make sense because it is a disease with clear auto-immune connections. All auto-immune disease is on the increase and this is supported by solid data.

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    2. In that case, we should look for something that has altered in all populations affected by such maladies and immediately quality of environment stands out as a common variable that seems to have deteriorated in multiple ways..the food we eat, the air we breathe, the water we drink and our sensory inputs. In developing world, this change has unfurled quite dramatically and the air does not smell like it used to even ten years back. Everybody laments fruits and vegetables have,become tasteless and when it rains neither can we hear the frogs croak nor can I smell the wet soil, the sweet smell produced by cyanobacteria.

      And this is only ten fifteen years I am talking about..all of us have not suddenly started smoking nor have suddenly started consuming unhealthy foods and it is not a fantastical lament about the loss of a way of life.

      If indeed there has been a statistically significant rise in autoimmune disorders and related pathologies, then environmental activism does seem to have a point. A potent increase in toxic overload and absence of natural protective cover to buffer the impact.

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    3. Certainly autism rate is increasing. I took my grandson to a pediatrican in my hometown when he was 11 months old. All through the 11 months he had excessive crying, poor sleep and poor feeding. He was the first one who suggested to check the milestones because problems in self regulation during infancy has high correlation with autism and ADHD. He also told that "as for as I know autism rate is increasing in the western countries. A good number of my doctor friends who settled in the western countries have children with autism. Here it is a rare disorder. I don't know what is going on there". My hometown has a population of 30,00,000 and he has a very busy practice for nearly 15 years. Even in India there are autism forums. Parents participate are educated upper middle and higher classes and city based. XY Clinic for autism of Dubai has opened a clinic in Bangalore. We have 2 Medmap
      doctors in India. In the lower middle and lower classes as well as rural and small town areas autism is rarely talked about. We have good number of malnourished children with poor health care in India. we have high number congenital deformities vitamin defeciency and anemia but less autoimmune disorder. But cancer rate is certainly increasing. I think along with environmental factors parents age and contraceptives are also causing something in autism.

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    4. At least five family members, all in their forties, have been diagnosed with idiopathic auto immune disorders and they are not related through blood ties so it's not exactly a genetic link. Although all are from upper middle class, highly educated, urban backgrounds, were not exposed to. Very high level of toxic overload during most part of their growing up years. There has been some sinister modification in urban environments in the last ten-fifyeen years, if we dismiss better diagnosis as a reason. The generation now in their forties in India were conceived when their parents were young and environmental conditions were not so pitiable. Clear and present danger!

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    5. A new study blames endocrine disruptors for many diseases as well as a lot of autism and ADHD:

      https://www.sciencedaily.com/releases/2016/10/161018103657.htm

      They claimed to use conservative numbers in their assessments. It would be interesting if there was some sort of biomarker related to endocrine disruptor chemicals that you could test for in already exposed pregnant mothers and children (the endocrine disruptors likely have long been flushed out of the body whereas heavy metals tend to accumulate so you would need an indirect method).

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  11. Peter,
    People who have low cholesterol may not have enough pregnenolone to produce progesterone. Do you think higher dietary cholesterol intake would do any good? Eggs for example, don't make you fat but they give cholesterol.
    Chromosome 3q29 is linked to both autism/learning difficulties and exceptional mathematical ability. Is there research concluding to anything useful?

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  12. I know oxytocin has been covered a lot so far on this blog, but a new research paper gives a possible twist in explaining sex-specific actions oxytocin might be having with regards to autism:

    https://www.sciencedaily.com/releases/2016/10/161014153212.htm

    One of the strains in Biogaia Gastrus specifically is supposed to help raise oxytocin levels in the body and brain and at least in my son I believe it has helped a bit with his anxiety (which if left unchecked seems to cause SIB, aggression if disturbed, etc.). In males (mice) oxytocin administration seemed to relieve anxiety, but in females it did nothing in this regard, though it did improve social behavior in females.

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  13. I know this was covered several pages back, but Dr. Frye just got a double-blind placebo controlled trial on high dose folinic acid for improving autism symptoms.

    http://www.nature.com/mp/journal/vaop/ncurrent/full/mp2016168a.html

    The paper is in Nature which is one of the most prestigious science journals and what I found interesting with regards to folinic acid supplementation in my son is the levels they used in this study which maxed out at 50mg per day. I only supplement 800mcg per day which is still 200% the RDA. I know in studies on pregnancy, there is research showing negative developmental outcomes if folate is low high in the mother's blood as well as negative developmental outcomes if the folate levels are too high (suggesting a Goldilocks zone for pregnant mothers).

    In children and adults, I have little knowledge of the pros and cons of megadosing folinic acid. Perhaps Roger Kulp could chime in since he seems to be the resident expert here on folate matters.

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