Thursday, 30 August 2018

Éric Fombonne on Sloppy Autism Statistics

The reason I have a short list of talented researchers as my Dean’s List for this blog, is because of the generally low standard of much you can read about autism, even sometimes from governmental bodies like the CDC (Centers for Disease Control and Prevention) in the in the US and NICE (National Institute for Health and Care Excellence) in the UK.

I suppose these days it’s just called Fake News

My contribution is to highlight the researchers I think are worth paying attention to.
When it comes to the prevalence of autism, Éric Fombonne is a researcher who has more than his share of common sense.  Fombonne is a French psychiatrist and epidemiologist who also worked in the UK and Canada before moving to the US.
He recently gave the interview below, which highlights glaring errors/weaknesses in reports which are picked up by the mass media and put forward as facts. 

“… the CDC does not attempt to assess everybody in a population. Instead, it looks in the medical and special education records of each child in a certain region to determine whether a child meets criteria for its surveillance definition of autism. Children with no relevant notations of social problems in their records are assumed not to have autism.”
“In a study designed to validate these, researchers found that between 20 and 40 percent of children who met the CDC definition of autism did not actually have autism”
“Another issue is that of every 100 children the CDC researchers determine to have autism, only 80 have a reference to autism specifically in their medical or school records. So, one in five 8-year-old children the CDC decides has autism had never been picked up as autistic by any professional. At age 8, how is this likely?”
“I led a team that verified autism diagnoses prior to inclusion in a neuroimaging study. Trained researchers performed independent state-of-the-art assessments of over 200 children with an existing autism diagnosis. At least 30 percent of these children turned out to not have autism. It was mind-boggling.”
“In my clinics 25 years ago, I remember explaining to parents who had no clue about autism why their child qualified for the diagnosis. Things have now reversed. Nowadays, some parents and professionals push for that diagnosis and resist a ‘not autism’ conclusion because it may come with less support.”

I did a while back do my own review of autism prevalence, based on two studies carried out by Éric Fombonne.
My conclusion then was that prevalence is about 1% and that you can split it roughly into thirds.
·      One third has severe autism, which we can also call SDA (Strictly Defined Autism), or DSM3 autism.  DSM 3 autism is what medical professionals called autism 30 years ago, when it was rare. At that time it appears that many people with autism were only given a diagnosis of mental retardation (MR), which recently became intellectual disability (ID). The number of people diagnosed with MR/ID has fallen substantially as the number of people diagnosed with autism has increased, a clear case of substitution. 
·      One third have true Asperger’s, by which I mean above average IQ, no speech delay in childhood, but with substantial issues getting on with typical people.

·      The remaining third are people without MR/ID or a high IQ, may or may not have had a speech delay, but face significant challenges interacting with the wider world.  Surprisingly many people who today hold an Asperger’s diagnosis have below average IQ.

While someone with Down Syndrome (DS) will fit the diagnostic criteria of MR/ID and quite possibly autism, I think giving multiple diagnoses is unhelpful.
It is clear from the statistics that doctors stopped diagnosing people with MR/ID and instead switched many of these people to an autism diagnosis. 
Autism really should be seen as just a catch-all observational diagnosis, pending an accurate biological diagnosis, like Rett syndrome, Mitochondrial Disease etc.

The increase in prevalence of SDA
Due to the broadening of the definition of autism from DSM3 to DSM5 and, as Fombonne highlights, the very poor application of those ever moving diagnostic guidelines, we are left unable to draw any reliable conclusions about any increase in prevalence of SDA.
I certainly cannot prove it, but I believe the prevalence of SDA has increased substantially and most likely will continue to rise as society moves further from where it came from. This takes us back to the idea of the holobiont/hologenome.

The hologenome concept of evolution, considers a human as a community, or a holobiont - the host plus all of its symbiotic microbes. The collective genomes of the holobiont form a hologenome.

This becomes very relevant in human disease because in modern life humans have become separated from part of their evolutional holobiont (symbiotic microbes).  As a result all kinds on immune disease have become more prevalent.

To reduce the incidence of future SDA, steps could be taken now, just like public health tries to reduce the incidence of future heart disease.
You cannot stop random genetic mutations that lead to features diagnosed as autism, but you can influence many of the environmental factors and very likely you could take protective measures to increase the robustness of the mother and baby’s defensive mechanisms.


  1. Hi, I am the mother of 11 year old Adam, who has re-diagnosed childhood autism for another disintegration disorder, precisely because of the hurduous reasons. And we also have PANDAS 6 years after the active phase, we still have elevated D1 and beta tubulin levels. And now we are waiting for a diagnosis of genetics from Slovenia where we are leaving our entire exom and the doctor has suspected Nicolaides-baraitser syndrome. But these diagnoses have not only evolved in parallel with our age, but Adam's development has changed

    1. Hajnalka, the SMARCA2 gene encodes a protein required for transcriptional activation of genes normally repressed by chromatin. People with Nicolaides–Baraitser syndrome will likely therefore have low levels of all the proteins encoded by those genes.

      Anomalies in limb development and the sparsity of hair would suggest to me that Wnt signalling may be disturbed. That is just what springs to my mind, but I am no doctor.

      This syndrome is often associated with microcephaly, the opposite of most “autism”.

      Once you get a definitive diagnosis, you may want to research SMARCA2 in detail to see which genes are miss-expressed and which signalling pathways are hypo/hyper. Given the rarity of this syndrome you will have to do a lot of work yourself.

      Some parents of children with very rare disorders create a research foundation. One reader of this blog has done this for Pitt Hopkins syndrome and now there is dedicated research on this very rare condition.

  2. At least in the USA, I think you could have a more objective test for autism by now that depended on biological factors, rather than observational ones, but that would mean many doctors and psychiatrists ceding control and likely their jobs for going this route. Since medical professionals write the diagnostic manuals, it is unlikely they will ever adopt objective autism evaluations, especially those relying on machine learning algorithms. This is kind of akin to the fantasy of lawyers who are the majority of people in elected government making more efficient laws which require less lawyers to be paid to navigate them.

    Really, the only way you are going to get better and more accurate autism evaluations is for someone to come up with a private company that goes around the orthodoxy and offers a low cost service that is accurate whether it be via blood tests or something like tracking pupil movement to pictures of human faces or else a combination of many objectively measurable factors.

    Just as you cannot expect lawyer politicians to reform themselves, you cannot expect the same from doctors and psychiatrists who are loathe to adopt technology that may shrink their influence, power, income and social status.

  3. I started to write a comment on this about 3 times and stopped. I will try to add something valuable to the discussion. The whole categorization is of 0 value to anyone. I cant imagine any person specifically or a position where this would be of help. Autism is an organic problem. Its like saying cancer. Great, of which organ? What type? Imagine if blood cancer patients went to the same doctor as lung cancer patients and would have the same categorization, same code in insurance forms, same therapies, same type of disability help...that is basically a 400 year setback in medicine. Its absolutely necessary to stop the ‘autism is mental disease’ train and I will not even mention the ‘neurodiversity’ nonsense. I mean, cancer is also just cell diversity. We know that a lot of the ‘knots’ which make autism are known, there are MANY ways to test in the first 3 months, from EEG to glutathione transferase, cytokines, pupil tracking etc. There is obviously no will to do that. It would make whole systems crash. It would obviously derail the whole mandatory vaccination system, it would call for personalized medicine, it would enable doctors to delve into enviromental triggers and that would be a whole other pandoras box. We have to look at the current system of human organization and see them as they are, and to be honest, I do not see that there is enough factors to make this happen. Maybe down the road as frequency increases but I actually don’t think even then. I have my own statistics system, I had to call 30 plus kindergardens in my city to find a group that could take my daughter because they only take one autistic child per group. The groups are on average 25 kids. i did not find one. I found one which was ok with having two. I actually became desperate at one point and started scouring for newly opening kindergardens so that she would be first and even there I failed.

    1. Tatjana, modern medicine is all about being evidence based. For evidence you need statistics and for meaningful statistics you need accurate diagnosis, based on measurable biological markers.

      Autism still does not even have reliable observational diagnosis and we are many decades away from accurate biological diagnosis for the majority of autism.

      It is not just autism, many chronic diseases are not optimally treated. If you are treating a 3 year old, as opposed to an 83 year old, I think medicine could make more of an effort to translate the science into therapy. In the meantime I will do it myself, for my n=1 example.

    2. I thought long and hard, answering this. I believe that this blog, which is so very rich in content, mentions only about 40% of the current, accurate and reproducible knowledge about biological markers in autism. A person who would really love to make a panel that could predicr autism in babies about 6 months old, could very well do so. As far as problems with observational diagnosis go, that is one thing which I fail to understand. I can spot autism with a glance over my shoulder. I once saw a child sitting still and without any special markers on his dads shoulder behind us in the airport and I knew. I once sat next to the pool in the holidays reading a book and a dad was playing with his 2 year old in the pool, and I knew. I saw a woman give her child a snack at the supermarket checkout and I knew. I even once saw a teenager sit content on a bench and was inexplicably drawn to him, thought that he had a special energy, and was very beautiful as a person. When I walked back, past that bench again, he was hand flapping. Most of these people I befriended. And if I can spot autism from a mile away, what is wrong with the people who are supposed to give an observational diagnosis? are they scared? I can tell you that in Israel, observational diagnosis happens between 6-9 months and early intervention starts straight away. Apparently, its possible. Everything is already possible. It will just not happen, because humanity is not really awesome.

    3. Tatjana, I also wonder how people make diagnosing autism so hard, but I am thinking about severe autism. The developmental paediatrician in London who diagnosed my son, gave us 2 options, just her for one price and a multi-disciplinary team assessment for twice the price. She said that she could diagnose autism based on a questionnaire and meeting the child once and not to waste your money. She was totally correct. I find it very odd that some people need multiple consultations over months/years.

      In reality people keep going back until they get the diagnosis they want, which these days is autism. Then some of the older people almost celebrate their diagnosis, as if a burden has lifted. You are still the same person.

      I think people are now often diagnosing borderline/trivial autism. Do you tell the parents their child is just a bit quirky/introverted, or give them a "medical" diagnosis? It is like getting antibiotics for a cold, some private doctors give them because the parent almost demands them.

      The big change is that in Anglo-Saxon countries in particular, parents actually want their child given an autism label. In many other countries doctors even pretend severe cases are not autism, "it is dysphasia and just wait until the child gets older".

      A crazy world.

    4. Hi Peter, I agree, my son was diagnosed at 2 years and a half in one our, during our first visit to the child psychiatrist, She wrote a note to the neurologist which i still have and said:"I saw Francisco who has ASD , he impressed me as intelligent and with potential for work"

    5. A small confession - I am one of those undiagnosed aspie girls. I just realized it when working through the topic with my child. Its a great plus because I understand her so well. The reason I am saying this is, yes, Peter, its a crazy world. I constantly get told that my child needs ‘more socialization’ in a world in which most people are crazy by my standards yet appear, compared to my daughter, well socialized. Its a big problem for me because it puts me in a spot where I have no idea who to trust - my instincts or them. I think a lot of the ‘strange’ things she does are completely normal. For example, she will not imitate a strange unknown person she sees for the first time. They always ask me ‘will she imitate on command’ and I say ‘if she wants to, if she knows you’ and they say ‘well that not on command’. As far as I am aware, when strange people come up to you and say ‘wave like this’, people mostly would not do it. But a child aplarently has to.

    6. Tatjana, if you look hard enough you will see mild traits of Asperger's in all intelligent people. The import thing is to be able to understand different types of people and to be able to accept different views, people who cannot do this will find life a struggle and annoy everyone else.

    7. I agree, being very rational at one point makes you go into the aspie zone. but I was a mensa member and honestly, everyone who thinks intelligence and education are THE thing should go to a few mensa meetings to meet some really messed up people. A LOT comes down to personality, morality, ethics, ability to self evaluate of the distinct ‘aspie’ memories from my childhood was 1. whenever adults told me ‘why dont you go do X, all the other kids are doing it’ I would look at them and fervently avait the BIG REVEAL, why other kids doing it had anything to do with me doing it. I honestly thought there was some adult reasoning behund it which I did not get. 2. I was put into school ar 6 since I was way ahead, and my kindergarden teacher was shocked because my social behaviour in the kindergarden was so closed off that she thought I had a development problem (not the one I had, a more severe one).

  4. Peter,

    I fully agree with you, as a kid I was first diagnosed with PDD-NOS, then later on Aspergers, and now Im diagnosed with Aspergers and ADHD.

    I dont get why genetic data is not allready properly recognized by doctors. I showed a replacement doctor a few weeks ago that I have a high chance of developing arthritis (in fact I allready have a lot of the symptoms, painfull joints when exercising and such) and he basically shrugged and told me it was no evidence at all.
    Its a joke, doctors are both too arrogant and dont see the accuracy with diagnosing that ONLY genetic information can give. This is purely arrogance on the side of doctors, you know the type... they like to be the one that knows it all and figured it all out.

  5. I guess this article was cited somewhere here before, but I can't remember seeing it:

    Neuronal Chloride Regulation via KCC2 Is Modulated through a GABAB Receptor Protein Complex.
    "We describe a novel association between the GABABR and the potassium-chloride cotransporter protein, KCC2. This association is significant because KCC2 sets the intracellular chloride concentration found in mature neurons and thereby establishes the driving force for the chloride-permeable GABAAR. We demonstrate that GABABR activation can regulate KCC2 at the cell surface in a manner that alters intracellular chloride and the reversal potential for the GABAAR."
    "we show that activation of GABAB receptors results in a decrease in KCC2 function"


    1. Ling, you are keeping busy.

      That paper is quite recent and is interesting. It shows how interrelated everything is. As the paper comments:

      "These findings reveal a novel “crosstalk” between the GABA receptor systems, which has important implications for the regulation of inhibitory synaptic transmission."

      In theory a brain-specific GABAb antagonist could be helpful for people with high levels of chloride inside their neurons. This would be the opposite of (ar)baclofen.

      But baclofen also stimulates growth hormones and for some people with autism this would be beneficial and this is why IGF-1 injections can be therapeutic in some types of autism.

    2. Very interesting paper Ling.

      I had to read the entire paper to make sure that was not a typo on their part. This is quite interesting because GABAB receptor activation is typically associated with inhibition, especially with regard to drugs that bind to the receptor as Peter already mentioned, but that it seems to act as a counterweight to GABAA receptors (according to this paper) would make sense in order to prevent excessive hyperpolarization of the cell membrane. One could envisage that drugs like Baclofen might work by desensitizing the GABAB receptors at a high enough concentration (this is just me hypothesizing as I have never read of any evidence of this before).

      Another thing that was interesting in this paper was the hypothesized signaling pathways relying on G-Protein receptors. A new paper on dopamine signaling where they were able to dissociate functions of the D2R receptor using this method might be applicable to GABAB receptors here:

      Press Release:


      With respect to dopamine, this is obviously important as D2R antipsychotics like risperidone are dirty drugs that affect all 4 major dopamine pathways in the brain (mesolimbic, mesocortical, nigrostriatal, tuberoinfundibular), so being able to segregate their downstream functionality at each part of the brain for very specific cells is highly desirable for developing drugs that do more good than harm.

      Last but not least, in this study the researchers only looked at GABAB receptors in the CA3 region of the hippocampus. As per the previous dopamine study mentioned, what GABAB is doing intracellularly in one type of neuron might be somewhat different than what it does intracellularly in another type of neuron, not to mention there are different subtypes and subunits of GABAB receptors.

    3. I have an old note of mine where GABAb is pictured as an inhibitor of cAMP and PKA, but I don't have the source for that left. Anyways, it looks like you are right Peter, GABAb antagonist are good for memory, at least in some models:

      "Data from this study indicated that intra-hippocampal microinjection of the GABAB receptor antagonist counteracts the learning, memory, and cognitive impairments induced by amyloid β."

      "the observed cognitive enhancement following CGP35348 (a GABAB receptor antagonist) in STZ-infused rats clearly indicates involvement of GABAB receptors in cognitive deterioration. Our results suggesting that the blockade of GABAB receptor would be a novel strategy to ameliorate cognitive dysfunction associated with neurodegenerative pathologies such as AD."

      "Together, the data agree that proper functioning of GABAB receptors is crucial for numerous learning and memory tasks and that targeting this system via pharmaceuticals may benefit several clinical populations"

      Unfortunately, I haven't found any obvious GABAb antagonist candidates for a DYI trial.


    4. Ling, apparently Ginseng is a GABAb antagonist.

    5. Peter, you are a star! :-)


    6. Supplementation of Korean Red Ginseng improves behavior deviations in animal models of autism

  6. I just finished reading "Imprinted Brain" by Christopher Badcock. It offers an alternate hypothesis of what may be causing the apparent increase of autism. It basically hypothesizes that autism is the mirror opposite of psychosis and that since famine increases the incidence of schizophrenia, then improved standards of living (higher birth weight) will cause increased autism. I personally hope this hypothesis is wrong since I think it'll be harder to treat/prevent autism, if it turns out to be true. A summary is here:

    1. In one of my fb groups a mom studied the SNPs of 20 people who have inflammatory conditions such as autism, pans, ms, mast cell issues etc. She came to the conclusion that they have what she calls ‘Famine Storage - High Inflammation’ type of altered genes. is the link for the video. I have not looked at it and it can be utter rubbish, I just found it interesting enough to mark into my ‘to see and evaluate’ pile.


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