Dr. Tom Insel on Demystifying Autism

12 May

Dr. Tom Insel wears many hats, as they say. He is the director of the National Institute of Mental Health (NIMH), one of the National Institutes of Health run by the US Government. As part of his function there, he chairs the Interagency Autism Coordinating Committee (IACC). The IACC prepares the “Strategic Plan” for the government’s activities in autism research.

Dr. Insel has obviously taken autism research very seriously. He doesn’t just chair the IACC, he obviously spends a lot of time reviewing autism research. I doubt many people at the Director level at NIH would spend the amount of time Dr. Insel obviously spends on autism.

He has recently given a few talks on autism, the current state of knowledge and the directions for research. One such talk was at NIH and was titled Demystifying Autism . Another talk was given at MIT and was hosted by the Simons Foundation. (sorry, I can’t find embed code for those talks)

Dr. Insel talks about how there is a large diversity in the autism population. The “spectrum” is broad, as likely most readers to this blog will already know. In both talks, Dr. Insel uses video from Dov Shestak (son of Portia Iverson and Jon Shestak, founders of Cure Autism Now, which is now part of Autism Speaks). This is used to give an example of regression in autistics.

Of course one large section is devoted to the increasing autism prevalence. Dr. Insel mentions the epidemiological work of Peter Bearman, which shows that much of the increase in the California Department of Developmental Services autism caseload can be accounted for by diagnostic changes and social factors. But, not all of the increase has been accounted for. Dr. Insel uses the term that the burden of proof is on those who would say that the increase is not “real”. I would put it differently–that given the lack of definitive information on the causes of the rise, we should continue to look for possible environmental causes. Many use the term “environmental cause” to mean “vaccines”. That’s not what I, or it appears, Dr. Insel mean though.

Dr. Insel discusses one yet-unpublished study: the California Twin Study.

Here is his power point slide (which you can click to enlarge if you wish):

Slide showing results of yet unpublished twin study

Dr. Insel's slide on Twin Study


Narrow criteria:
monozygotic (“identical”)–80% concordance
dizygotic (“fraternal”)– 26% concordance
broad criteria
monozygotic–87% concordance
dizygotic– 39% concordance

This is consistent with a recent study from the Kennedy Kreiger Institute at Johns Hopkins. While this wasn’t discussed by Dr. Insel, I include the abstract for that study below:

OBJECTIVES: To examine patterns of autism spectrum disorder (ASD) inheritance and other features in twin pairs by zygosity, sex, and specific ASD diagnosis. DESIGN: Cross-sectional study. SETTING: Internet-based autism registry for US residents. PARTICIPANTS: Survey results from 277 twin pairs (210 dizygotic [DZ] and 67 monozygotic [MZ]) aged 18 years or younger with at least 1 affected twin. MAIN EXPOSURES: Zygosity and sex. OUTCOME MEASURES: Concordance within twin pairs of diagnosis, natural history, and results from standardized autism screening. RESULTS: Pairwise ASD concordance was 31% for DZ and 88% for MZ twins. Female and male MZ twins were 100% and 86% concordant, respectively, and DZ twin pairs with at least 1 female were less likely to be concordant (20%) than were male-male DZ twin pairs (40%). The hazard ratio for ASD diagnosis of the second twin after a first-twin diagnosis was 7.48 for MZ vs DZ twins (95% confidence interval, 3.8-14.7). Affected DZ individual twins had an earlier age at first parental concern and more frequent diagnoses of intellectual disability than did MZ twins; MZ twins had a higher prevalence of bipolar disorder and Asperger syndrome and higher concordance of the latter. Results of autism screening correlated with parent-reported ASD status in more than 90% of cases. CONCLUSIONS: Our data support greater ASD concordance in MZ vs DZ twins. Overall higher functioning, psychiatric comorbidity, and Asperger syndrome concordance among affected MZ vs DZ twins may also suggest differential heritability for different ASDs. For families in which one MZ twin is diagnosed with ASD, the second twin is unlikely to receive an ASD diagnosis after 12 months. In addition, Internet parent report of ASD status is valid.

Concordance is when one child has an ASD, does the other one? 100% concordance would mean that if one twin has an ASD, the other twin does as well. That would indicate that autism is purely genetic.

Most people will concentrate on the monozygotic concordance. Even with the broad criteria, there is 87% concordance. That would indicate that at least some fraction of the cause of autism is not genetic. This is a very complicated question, as Joseph at the Autism Natural Variation blog has discussed.

What is astounding to me is the dyzogotic concordance. Take the 39% for the broad criteria. My recollection is that the concordance for siblings is about 4% if one sibling is male, and about 10% if one sibling is female. I’m trying to find the study on this. But, is there a higher concordance for dizygotic twins than for siblings in general?

Dr. Insel spends a fair amount of time on the genetic studies involved in autism. He attributes about 15% of the current autistic population as being linked to known genetic conditions. This is a pretty common estimate in the community.

One interesting fact: the known genes associated with autism are neurodevelopmental and involved with synapses. He even titles the slide as “Autism as a synaptic disease” and proposes that synaptic function might be the unifying feature of autism.

Dr. Insel notes that there are many chemicals whose neurotoxicity have not been determined. He also notes that there are some known chemicals which increase the risk of autism–valproic acid, Thalidomide and misoprostal. For all of these there is a critical window of time–in the first or early second trimester of pregnancy–where the autism risk is increased. Thalidomide, for example, is considered to be causal in a short period of time–from 20 to 24 days gestation.

If you want to see the direction Dr. Insel may take autism research in the future, these talks are worth listening to. I think it safe to say that autism research will continue to look for causes, genetic and environmental. Environmental cause research will likely focus on prenatal exposures. Study will continue on the physical structure of the brain, the “circuitry” to help define what autism is and what the phenotypes may be. Study will continue on interventions, with a look towards earlier interventions (before age 1, possibly before symptoms are visible). Intervention research will look to be tailored to the individual, which will require some way to phenotype autism.

As I noted above, I think Dr. Insel is taking a close interest in autism. He doesn’t dictate the goals for autism research, but I think listening to what he has to say gives in interesting insight into the directions it may be going.

9 Responses to “Dr. Tom Insel on Demystifying Autism”

  1. passionlessDrone May 12, 2010 at 14:48 #

    Hi Sullivan –

    Nice posting.

    Regarding the discordant findings between twins, I would recommend you check out a series of papers by Valerie Hu and others that performed genetic expression analysis on identical twins that were discordant for autism severity and found differences in which genes were being expressed. They have several papers on this, with Global methylation profiling of lymphoblastoid cell lines reveals epigenetic contributions to autism spectrum disorders and a novel autism candidate gene, RORA, whose protein product is reduced in autistic brain being the most recent.

    It is really cool stuff. The paper I linked to above has the additional coolness factor in that they used cells from the periphery as proxies to perform targeted analysis for genetic expression in autistic brain tissue.

    – pD

  2. Carlos Useche May 12, 2010 at 14:48 #

    In reference to a new drug designed to fix the molecular defects in fragile X helps some patients.

    “Just three years ago, I would have said that mental retardation is a disability needing rehab, not a disorder needing medication,” Dr. Thomas R. Insel, director of the National Institute of Mental Health, told the NYT. “Any positive results from clinical trials will be amazingly hopeful.”


  3. daedalus2u May 12, 2010 at 17:19 #

    Here is a link to the MIT talk. I was there in the audience and the talk was excellent. I especially liked where he says he thinks that the human microbiome is involved and that the increase in childhood allergies is the only thing that parallels the increase in autism.


    I think both are caused by low NO due to the loss of the bacteria I am working with.

  4. daedalus2u May 12, 2010 at 17:25 #

    The thing that fraternal twins share that siblings do not is an in utero environment. To me, this clearly points to the in utero environment as a major factor in autism.

    Identical twins share an in utero environment too. To me, that means that some of the concordence in identical twins is not from their shared genetics, but from their shared in utero environment (see fraternal twin excess).

  5. Joseph May 12, 2010 at 18:29 #

    What is astounding to me is the dyzogotic concordance. Take the 39% for the broad criteria. My recollection is that the concordance for siblings is about 4% if one sibling is male, and about 10% if one sibling is female.

    That was also my impression from older studies: very low DZ concordance, and high MZ concordance. The implication was that autism couldn’t be explained by a single allele, otherwise you’d expect close to 50% DZ concordance.

  6. Ian MacGregor May 13, 2010 at 14:25 #

    Does anyone know if Dov Shestak typing skills have been validated? The communication looks facilitated as the keyboard itself is being moved. However, if this is an example of FC, the technique is quite different from the facilitator guiding the person’s hand.

    Dr. Insel fully accepts this ability, and uses it as an example of how a person with autism had his intelligence misjudged due to his inability to speak.

  7. Carlos Useche May 15, 2010 at 15:44 #

    Check this out: Genetics of Autism, Prof. Matthew State

  8. Katie May 16, 2010 at 14:38 #

    While I’m certainly interested in this research and very glad to see that the iacc isn’t devoting funds to prove for the thousandth time that it ain’t the vaccines, I’d still like to see less money go to causation and much more be devoted to research that can actually help autistic people who are here now. Try justifying this research to An autistic child who is abused in school or an adult who sits at home because no services are available. Try telling a person who can’t commnicate because there are no appropriate AAC devices for him, ” good news! We now know what the autism concordance rate for monozigotic twins is 80%!”
    I certainly don’t mean to belittle this research (honest science is always better than quackery), I just can’t justify so much of it when people alive now are suffering and so little research is being done that will have a practical and positive impact on their lives.


  1. Tweets that mention Autism Blog - Dr. Tom Insel on Demystifying Autism « Left Brain/Right Brain -- Topsy.com - May 12, 2010

    […] This post was mentioned on Twitter by Kev, shannonrosa. shannonrosa said: Dr. Tom Insel proposes that synaptic function might be the unifying feature of #autism. http://bit.ly/blvjqf via @kevleitch […]

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