Friday, September 30, 2011

Combating Autism Act Renewed

The bill reauthorizing the Combating Autism Act for another three years was signed into law today by President Obama.  This bill will provide 693 million dollars over the next three years for funding research, surveillance, and education activities related to autism.

If you are interested, there is more information about the history of the re-authorization under both the initial Senate bill S.1094 and the final House bill H.R.2005 that was passed into law.  There is also a breakdown of the costs provided by the Congressional Budget Office.

The text of what the Combating Autism Act is available here.  If you aren't familiar with what the Combating Autism Act is and isn't, you might want to take the five minutes to read what it is meant to accomplish

On a slightly infantile note, I would like thank the Autistic Self Advocacy Network (ASAN) for their hard work in opposing this important legislation. Their misunderstanding and misrepresentation of this bill came to nothing and the bill was passed in spite of their objections.

So to ASAN I would just like to say.

Nana-nana boo-boo

P.S. Yes, I understand that services and supports for adults with autism are an ever increasing and urgent need.  But did ASAN really have to campaign against badly needed research into the nature of autism and educational services for children?  Whose needs do you think that ASAN is advocating for because it sure isn't the needs of the majority of people with autism.

Wednesday, September 28, 2011

Jabberwocky of the Day : John Elder Robison on the Male Female Autism Imbalance

As was first pointed out on Autism's Gadfly, John Elder Robison is once again talking about things that he doesn't seem to have the faintest clue about.  Last time, Mr. Robison was making completely inaccurate statements about CDD.  This time, Mr. Robison is talking about the the fact that autism is far more common in males than females and coming up with some rather far fetched ideas to explain the discrepancy.

As most of you probably know, autism is about four times more common in boys than girls.  This gender skewing was first noted all the way back in the 1940s when Kanner "invented" autism and has remained a constant property of autism even as as the number of children with autism has exploded from 1 in 10,000 in the 1940s to 1 in 100 today.

What you may not know is that a similar gender skewing is commonly seen in other childhood disorders as well, such as ADHD and intellectual disability.  The exact ratio of boys to girls changes with the disorder but in general boys are more likely to have a developmental disorder than girls.  So, in reality, there doesn't seem to be anything that different about autism in this regard.

The question is then why are boys more likely than girls to have development disabilities.  In my opinion, the general answer to that question is built into the question itself.  Obviously, there is some different between males and females that either makes males more susceptible or females less susceptible to these conditions.  Either the reason is genetic, biological, social, or (most likely) some combination of the three.

The trick has always been to identify the causes of the conditions and then to work backwards to determine why males are more affected than females.  But since, when it comes to autism (and ADHD), we don't have any real clue as to what the the cause of the condition is, we don't have any real clue as to why the difference is there.

But that doesn't stop Mr. Robison from coming up with some rather, uhm, interesting ideas about why this difference exists.  He first seems to suggest that families with children on the spectrum are more prone to having boys than girls -
If we assemble a collection of families in which there is at least one autistic child, that distribution of sons and daughters is not 50/50.  It favors the males.
But I have never run across any study that has even suggested that families who have children on the spectrum are more likely to have boys than girls.  This claim would go against the generally held (and proven) idea that the chance of having a boy or a girl is roughly 50/50.

It would be a fairly simple matter to survey a large number of families who have with multiple children where at least one child has autism and see if this were true.  But I would like to think that, if this claim were true, someone would have noticed the discrepancy and published on the subject by now.

In fact, the largest autism sibling study to date that was published just this year and included data on 664 sibling showed (roughly) the expected 50/50 breakdown between the genders.

Who knows, maybe Mr. Robison's proposed relationship has been demonstrated in other studies and I just missed it.  But if so, I think he needs to show us the data and not just make unsupported statements.

Next, Mr. Robison goes on to show an astounding ignorance of basic chance when he suggests that -
One explanation is that some parents have a son with autism and stop having children.  So the girls that might even the male/female ratio are never born.  I think that explanation may be true today, but what about the ages before modern birth control?
Frankly, I don't even understand how this could work.  It seems like Mr. Robison is suggesting that first born children are more likely to be a boy than a girl but that idea is just plain nonsense.  The chance of having either a boy or a girl in any given pregnancy is almost 50/50.  That fact is as true for the first child as it is for the last child.

Maybe he is suggesting that a first born boy is more likely to have autism than a first born girl but then the chances even out after the first child?  But that would not make any sense either.  If boys and girls both had the same chance of having autism then you would have the exact same chance of having a first born boy with autism as you would a first born girl.

Then Mr. Robison makes some rather strange claims about the "historical record" (i.e. pre 1940) of people with autism -
Critics might say that we don’t know how autism was distributed among the sexes a hundred years ago, and that’s true.  The autism diagnosis has only existed for sixty-some years.  Yet we do have strong anecdotal evidence.  Using that, some modern day people have “diagnosed” historical figures with autism based on what we know of them and their lives.  How many of those individuals are female?  Almost none.
Those “post-mortem diagnoses” are certainly subject to challenge and I’m sure some are even wrong.  That said, they can’t all be wrong and the male-female ratio in the known historical record of autism remains strikingly tilted toward the male side.
There are so many things wrong with this argument that it is hard to know where to begin.

Perhaps the worst part is the idea that a post-mortem diagnosis is evidence of anything besides someone having way too much time on their hands.  You simply cannot diagnosis someone based on little snippets of what is published about their life.

It is hard enough to diagnosis an adult with high-functioning autism who is sitting in front of you with their parents and has a complete record of their development.  When you add in a span of hundred years or so, several changes in culture, a selective report of only parts of their life, and the inability to talk directly to the person, then making an accurate diagnosis becomes next to impossible.

Then the idea that "they can't all be wrong" is just silly.  Yes, every post-mortem diagnosis can be wrong and, given the challenges in making an accurate historical diagnosis, I would be willing to bet that almost all (if not all) of them are in fact wrong.

And calling a post-mortem diagnosis "strong anecdotal evidence" does a disservice to the word "strong" as well as the word "evidence".  The idea that speculation based on extremely limited historical information is actually "anecdotal evidence" let alone "strong" is just absurd.

But, for the sake of argument, lets assume that these absurd statements are true and that the historical record does have more males than females with autism.  Does that tell us that there were more males than females in the past or does it tell us that, historically, men were much more likely to be written about than women?

Anyone with even a cursory knowledge of historical literature should know the answer to that question.

Perhaps the only intelligent thing that Mr. Robison has to say on this subject is that idea that female fetuses with autism are less likely to survive -
Geri Dawson suggested another possible explanation for the male-female imbalance.  What if girl embryos are actually more susceptible to some factor implicated in autism, but in a different way?  The factor that produces autistic baby boys might result in unsuccessful pregnancies when the fetus is female.  The result – fewer baby girls with autism are born
If this idea repeated by Mr. Robison is correct then you would expect to see a noticeably higher rate of autism in children with prenatal complications.  Having a history of miscarriages means that you have a greater chance of having complications in future pregnancies.  But the most recent study of the topic suggested that there is no such broad association.

Furthermore, in some of the known genetic causes of autism the exact opposite happens - the male child is either more effected or has a lesser chance of surviving.  A male child with Rett Syndrome is very unlikely to survive while a female can because of her double X chromosome.  And in Fragile X, a female is somewhat protected against having the symptoms of the disorder, again because of genetic differences.

So, if anything, I think this idea might be correct if it was flipped.  Rather than female fetuses not surviving, it seems more likely that being female offers some sort of protection against developing autism as well as other development disabilities.

But again, maybe there is data out there that shows a higher rate of miscarriages in mothers who children have autism.  But to me it sounds like grasping at straws.  Perhaps it would be better to have some actual concrete data to support a claim rather than just idle speculation.

I think the most disturbing part of all of this isn't the nonsense itself but rather Mr. Robison's position at Autism Speaks.  It doesn't really matter than he has some really strange ideas about autism or that he seems to misunderstand some basic science.  We all have areas where we are less than knowledgeable but still like to pretend we know what we are talking about.

No, I think the most disturbing part is that Mr. Robison serves on the scientific advisory board of Autism Speaks and helps select what science they will fund.  If a non-expert like myself can see the gaping holes in his ideas then what does that say about the projects he would suggest funding?

Friday, September 23, 2011


I know that this isn't autism related, but scientists with the OPERA experiment are saying that they might have observed a small particle called a neutrino traveling faster than the speed of light.  If this result is true then it will overturn much of what we think we know about how the universe operates.

As astounding as that result would be if it were found to be true what I think is more astounding is how the scientific community is responding.  Here you have something that would overturn decades of dogma and challenge everything that we think we know and yet the reactions are cautious and balanced.

I haven't seen anyone spouting off about how we "know" this result can't be true or how this question has been asked and answered already.  No one seems to be launching personal attacks against the scientists involved.  And no one seems to be overselling the result or claiming that this result "proves" that all we think we know about physics is wrong.

In short, the parties involved seem to be acting in a rational, scientific manner.  They found a result that they didn't expect and are seriously examining it to see if it is true - even though it goes against everything that they think they know about physics.

Only time well tell if the speed of light isn't the absolute limit that we though it was but scientists acting like scientists is a nice refreshing change.

Now if only the world of autism could do the same.

Thursday, September 22, 2011

Study: Immune System Disruption Implicated in Autism

There have been a couple of good studies published in recent weeks that look at the possible connection between disruptions of the immune system and autism.  But one in particular that was published just last week in PLoS One looks to be the best of the bunch.

I have not read it in depth yet so I might be getting some of the details wrong.  But in general, it looks like these researchers managed to take the many rare genetic mutations that have been seen in autism and demonstrate that many of these mutations converge on biological paths that control immune system signaling.  The researchers suggest that these disruptions have the potential to alter typical brain development and lead to the symptoms of autism.

I would normally include the abstract of the study but I think these paragraphs from the conclusion puts the findings into prospective -
Interestingly, there is also mounting evidence at the cellular and tissue levels that more in depth investigation of an immune component is warranted in ASD. For instance, multiple studies have demonstrated altered cytokine profiles in ASD patients, and altered TGF-B concentration in serum and CSF correlates with disease severity. Others have described various autoimmune phenomena including autoantibodies to neural antigens and maternal-fetal cross-reactive neural antibodies. There is also indication of altered innate cellular immunity in ASD, such as differences in gene expression and altered response to immunostimlulatory ligands in both natural killer and monocytic cells from ASD patients. Post-mortem brain tissue from ASD patients shows increased microglial density in grey matter, an activated morphology, and secretion of a cytokine profile consistent with a pro-inflammatory state, most prominent in the cerebellum. Moreover, microglia from MeCP2- null mice—a model of the Autism Spectrum Disorder Rett Syndrome—produce a conditioned media that damages synaptic connectivity via a glutamate-excitotoxicity mechanism. While all of this work provides post-hoc evidence for altered immune response in ASD, our results suggest a direct link between implicated genes in ASD and molecular pathways involved in immune signaling.
This considerable attention to the immune response in previous ASD research has resulted in two prevailing theories: one suggests exogenous factor(s) stimulate neuro-inflammation during development, while the other postulates autoimmune activation causes ASD pathology. However, it is equally possible—as our results support—that the mutations described in ASD result in aberrant signaling regulation of immune cells during neurodevelopment. This could result in cell-autonomous activation and/or improper response to otherwise nominal stimuli, such as occurs in the autoinflammatory syndromes. Alternatively, as glia are increasingly implicated in normal formation of synaptic connectivity —and we have demonstrated a significant proportion of ASD-implicated genes appear to be glial-specific—it is possible that genomic aberrations ultimately funnel through core signaling pathways of glial cells to disrupt formation of neural networks independent of an inflammatory mechanism. In support of this notion, a number of recent reports have demonstrated that these same cytokine signaling pathways are central to proper brain development. Furthermore, signaling through the NFkB pathway has been shown to be important in synaptic plasticity independent of an inflammatory mechanism.
The study is open access so go read it if you are interested in the subject.


Ziats MN, Rennert OM. Expression Profiling of Autism Candidate Genes during Human Brain Development Implicates Central Immune Signaling Pathways. PLoS One. 2011;6(9):e24691. Epub 2011 Sep 15.
PubMed PMID: 21935439. DOI: 10.1371/journal.pone.0024691

Friday, September 16, 2011

Treating Autism : The First Five Years

This summer and fall has been somewhat of a transition time for my family.  The twins, after a year delay, have finally left the early intervention system and are now in kindergarten.

It might be too early to call it, but it seems like the twins have made the transition from the one on one supports that they have been receiving for years to the public school system without too many problems.  They are still receiving special educations services and spend at least half of their time in a support classroom but they are also spending a great deal of time in the mainstream classroom as well.

Baby C, even though she two years younger than her sisters (OK, she really isn't a baby anymore), will be following her sisters into kindergarten next year.  I expect that Baby C will be able to make the same sort of graceful transition next year that her sisters did, although that is certainly not a given.  She is higher functioning but has more behaviors to contend with than her sisters do.  But that is a story for another time.

It has taken the twins and us five long years of work to get to this point and, while we had once hoped that they would be "recovered" from their autism by now, they certainly have come a very long way.  If you compared what they looked like and how they acted back them to what they do now you might not even think they are the same children.

Six years ago, the twins were normal babies.  They were developing at the typical speed and meeting all of their milestones at the appropriate time.  Or I should say that they were meeting all of the milestones at the appropriate times for twins, twins do develop differently than single babies.  We had no reason to think that anything was wrong.

About six months after that they started to change.  Their development stalled (for a lack of a better word) and they started slowly developing the symptoms of autism.  I talked about this period in their lives a few months back, so I am not going to rehash it now.

Five years ago when they received their autism diagnosis, they were very different than they were just six months earlier.

They did not look at people, they did not point, they did not understand or show emotion, nor did they respond to voices or any other sounds.  For a while there we (and several audiologists) though that they had gone deaf.  You could walk up behind them and scream at the top of your lungs and they would not show any sort of reaction whatsoever.  They certainly weren't responding to either verbal or non-verbal communication.  Nor could they talk or imitate any sort of sounds.

Interestingly enough, at this point they had very few rigidities or restricted interests.  They did a little bit of stimming but that much more than a "typical" child does.  Their rigidities and restricted interests didn't really become noticeable until a few years later.

They also had some health problems.  They both had almost constant runny noises and were sick quite frequently.  They had almost constant eczema.  They had an extremely limited diet and, not to be gross, their stools were not what they should be.

If you look at the twins now, they do make eye contact and can read emotions from people's faces.  They still can't talk very well (one to two words at a time) but their verbal and non-verbal communication skills have developed.  On a good day they are only a year or two behind where they should be in receptive communication.

They don't have the social skills that they should but they do interact with adults and children as best as they can.  Even better, they are showing an interest in other people and sometimes are trying to be social.  Over the summer, one of the twins walked up to a peer and said "Hi" to them completely independently.

To those of you who don't deal with moderate to severe autism that might seem like a trivial thing, but to those of us who do, something like that makes your entire week.  Not to go off on a tangent but I think that is one of the reasons that adult self-advocates drive me to distraction.  They are out there pontification about how autism is just a neurological different and not a disability and here we are (and many families like us)  just happy that our children made an attempt to talk to another child.  It is two completely different worlds.

But enough about that, the real point here is how we got from where we were five years ago to how we got here.

Over the past five years, we have gone from denial to hope for a quick cure to the understanding that helping a child deal with autism isn't a sprint to the finish line.  It is a long drawn out affair that will take dedication, years of work, and no small amount of luck.  And even after all of that, there is no guarantee that anything you do will make the slightest dent in the autism.

Over the past five years we have waged a constant war against obsessions and rigidities that had appeared and threatened our girl's ability to function on their own.  After we let one or two obsessions develop to the point that they became real problems in everyday life (anyone else have a child who refused to walk in public for a year straight?) we learned that we had to act quickly when the behaviors first appeared and stop them from becoming a problem.  You can't - and shouldn't - break all of the behaviors, but you certainly have to break the ones that interfere with their ability to function.

We also spent three long winters tackling extreme mood swings and self-injurious behaviors in one of the twins until we finally understood that she had something like seasonal depression and treated it as such.  All it took (and still takes) to "cure" these problems is a little while sitting in front of a really bright light in the morning and a small dose of melatonin in the evening.

But probably the most important thing that we did was accept the fact that "mainstream" (pediatric) medicine doesn't have a lot to offer children on the spectrum.  Don't get me wrong here, I am a very firm believer in following the science and actually having something substantial and real behind what you do (as you should be able to tell from the other posts here).

But, when it comes to autism, mainstream medicine tells you exactly two things.  First, it tells you that there is no possible relation between autism and vaccines.  Second, it says that some ambiguous thing called early intervention is the key to a better future.  But it certainly doesn't define exactly what this early intervention is or what forms of early intervention will work best for your children.

Five years ago, we walked out a well known children's development center with a shiny new diagnosis and a stack of papers with phone numbers.  The good people at the center were kind enough to inform us that our twins had autism and give us a stack of scripts for doing some standard tests.  They did not help us pick which specific therapies would be appropriate for our children nor did they even tell us which of the many providers on the stacks were any good.

Making these difficult choices was left completely up to us.  Even though neither my wife nor I knew the first thing about picking a style of behavioral therapy, occupational/physical therapy, or speech therapy, we were left completely on our own to find our own way.

Luckily for us (and even more luckily for the twins), we had an extensive support network that we could draw on to help us find our way through the process and select appropriate therapies for our children.  But even with that we have had some good experiences and some bad.

And that is as far as the mainstream took us - behavioral therapy (ABA), speech, and OT.  Although the OT has been less than helpful for most of the time and the speech wasn't much better for the first three years.

I have to say though that without the ABA the twins would not be entering kindergarten the way they are now.

But if we had left it at that they twins would not be were they are today either.  We took it a step further and found people who helped us deal with the other biological issues that twins had.  We have used treatments that some would label as quackery or woo.  Some of them of worked, some of them haven't, but there was a specific reason that we tried each and every one of them.

We have used three biomedical treatments that I believe have played a large role in allowing the twins to progress as far as they have - the gluten-free, casein-free diet, zinc supplements, and melatonin.  There are a slew of other things that they have taken and still take that help to a greater or lesser degree but those are the big three.  If you take one one of those three away, the twins would probably not be where they are today.

This is one area were the "science" based crowd drives me nuts.  They are out there saying that there is "no evidence" that these things work and therefore they don't work and you shouldn't try them.  While it is true that these treatment are not supported by large scale trials and don't have proof" that they are an effective treatment for autism, this lack of evidence does not mean that they can't or don't work.

Like so many other things when it comes to autism, the answer for whether something will work for your child is it depends.  It depends on the specific symptoms of autism that your child has and whatever biological problems they have going on.

If we had listened to the "science" people then our children would not be were they are today.  My opinion is that if you have a solid reason for trying something (and not just because so and so suggested it), understand the possible benefits as well as the risks, and are can try it safely, then don't limit yourself to what "mainstream" medicine thinks is true.  And don't listen to the "no evidence" crowd either.  Instead, spend some time learning about the subject, talk to some people who actually understand the subject, and make and informed decision about whether it is appropriate for your child.

Over the past five years we have also tried to accommodate the twin's sensory needs.  The idea that children with autism have broken sensory mechanisms is something that mainstream medicine is finally now beginning to wrap their heads around.  It will be another ten or fifteen years before there are any real options "evidence-based" sensory treatments.

In the meantime, parents will continue to try anything and everything to help their children regulate better.  For the twins, their big sensory need (right now) is to be immersed in water.  They love taking a bath every day and they absolutely love being able to go swimming everyday (just don't tell they we are going to have to close the pool in a few more weeks).  We only hit on this need for water last summer but the effect is rather amazing.  If you give them 30 minutes a day in water then they are more relaxed an are better able to concentrate.

Along the way to finding this need for water we tried the weighted vests, weighted blankets, lights, sounds, lack of light, lack of sound, deep pressure, etc, etc, etc.  Some of these things worked, some worked for a time, and some did absolutely nothing.

And of course, probably the most important element in the twins growth is their willingness to work.  If they were not willing to apply themselves them no amount of therapy, biomedical treatments, or sensory help would be able to do anything.

Looking back over the past five years, I think the thing that has made the most difference is the willingness to try new things and to adapt to the every changing challenges of autism.  While five years ago I might have wished for my children to be "typical" by now, I am very proud of all of the things they have been able to accomplish in spite of having the disability called autism.  I only hope that in another five years I can say that they are still making the same sort of progress.

Saturday, September 10, 2011

Induced Autism

I ran across a recently published paper the other day that had a long title that didn't make much at first glance - "Prenatal exposure to ß2-adrenergic receptor agonists and risk of autism spectrum disorders".  According to the abstract1, this paper looked at exposure to ß2 adrenergic receptor agonists during the prenatal period and found that, in general, they did not increase the risk of having a child with autism.

So at first I though it was simply yet another paper ruling out a relationship between a type of drug and autism.  But then there was this little line that caught my attention -
However, terbutaline exposure for > 2 days during the third trimester was associated with more than a fourfold increased risk for ASDs independent of indication although the limited sample size resulted in an imprecise and nonsignificant effect estimate (OR(adj) = 4.4; 95% confidence interval, 0.8-24.6).
I didn't know what terbutaline was (or for that matter what a ß2 adrenergic receptor agonists was) but a four fold increase of autism is nothing to sneeze at.  So I exercised my google Phd and went and found out that, in general, ß2 adrenergic receptor agonists are a class of drugs that are used to treat asthma and other lung problems and that terbutaline is just the name of a specific drug of this type.

But it turns out that terbutaline is/was also used, off-label, to delay preterm labor.  So here you have a drug that has been used to delay preterm labor that might greatly increase the risk of autism.  That definitely isn't good.

On the flip side, this result is based on a small number of cases so can't just assume that the relationship is going to be the same in the general population.  But then again, this isn't the first study to suggest that neonatal exposure to terbutaline might increase the risk of autism.

Other studies have found that fraternal twins who were exposed to terbutaline for longer than two weeks had an increased chance of both having autism2, that rats who were exposed to a large dose of terbutaline showed signs of neuroinflammation3, and that certain forms of genes related to the beta2-adrenergic receptor might be more common in people with autism4.

So while there is some room for doubt, I think it is safe to say that the risk is real.  Prolonged prenatal exposure to terbutaline probably does increase the risk of autism.  The good news is (if any of this can be good) that the FDA issued a warning earlier this year about prolonged use of terbutaline for treating preterm labor -
The U.S. Food and Drug Administration is warning that terbutaline administered by injection or through an infusion pump should not be used in pregnant women for prevention or prolonged (beyond 48-72 hours) treatment of preterm labor due to the potential for serious maternal heart problems and death. In addition, oral terbutaline tablets should not be used for prevention or treatment of preterm labor. The FDA is requiring the addition of a Boxed Warning and Contraindication to the drug prescribing information (labeling) to warn against these uses.
Hopefully the medical community will get the message.


1. Croen LA, Connors SL, Matevia M, Qian Y, Newschaffer C, Zimmerman AW. Prenatal exposure to ß2-adrenergic receptor agonists and risk of autism spectrum disorders. J Neurodev Disord. 2011 Aug 27. [Epub ahead of print]
PubMed PMID: 21874331 DOI: 10.1007/s11689-011-9093-4 (Open Access)

2. Connors SL, Crowell DE, Eberhart CG, Copeland J, Newschaffer CJ, Spence SJ, Zimmerman AW. beta2-adrenergic receptor activation and genetic polymorphisms in autism: data from dizygotic twins. J Child Neurol. 2005 Nov;20(11):876-84.
PubMed PMID: 16417856

3. Zerrate MC, Pletnikov M, Connors SL, Vargas DL, Seidler FJ, Zimmerman AW, Slotkin TA, Pardo CA. Neuroinflammation and behavioral abnormalities after neonatal terbutaline treatment in rats: implications for autism. J Pharmacol Exp  Ther. 2007 Jul;322(1):16-22. Epub 2007 Mar 30.
PubMed PMID: 17400887 DOI: jpet.107.121483 (Open Access)

4. Cheslack-Postava K, Fallin MD, Avramopoulos D, Connors SL, Zimmerman AW, Eberhart CG, Newschaffer CJ. beta2-Adrenergic receptor gene variants and risk for autism in the AGRE cohort. Mol Psychiatry. 2007 Mar;12(3):283-91. Epub 2007 Jan 2.
PubMed PMID: 17199132 DOI:

Friday, September 2, 2011

Study : Are thyroid hormone concentrations at birth associated with subsequent autism diagnosis?

Thyroid problems at birth might be associated with an increased risk of autism.  Can anyone say endocrine disrupting chemicals?

For more details about what can disrupt the endocrine system and what the results might be, I would suggest reading this statement on endocrine disrupting chemicals from The Endrocine Society.

Are thyroid hormone concentrations at birth associated with subsequent autism diagnosis?
Autism Res. 2011 Aug 31.
Hoshiko S, Grether JK, Windham GC, Smith D, Fessel K.

Environmental Health Investigations Branch, California Department of Public Health, Richmond, California.

Thyroid hormones substantially influence central nervous system development during gestation. We hypothesized that perturbations of early thyroid profiles may contribute to the development of autism spectrum disorders (ASD). Thyroid pathways could provide a mechanism by which environmental factors that affect the thyroid system may impact autism occurrence or phenotypic expression. We investigated whether thyroxine (T4) levels at birth are associated with subsequent ASD, using two existing California study groups in multivariate analysis. One study group included children born in the San Francisco Bay Area in 1994, with cases identified through the California Department of Developmental Services (DDS) and/or the Kaiser Permanente Medical Care Program of Northern California (244 cases, 266 controls); the other included children born in California in 1995, with cases identified through DDS (310 cases, 518 controls).  Matched controls were selected from birth certificate records. This exploratory analysis suggested that infants with very low T4 (<3rd percentile) may have higher ASD risk, although results reached statistical significance only for the 1995 study group (1995: OR = 2.74 (95% CI 1.30-5.75; 1994: OR = 1.71 (95% CI 0.57-5.19). A variety of alternate analyses were conducted with available data, without further resolution of the difference between the two study groups. The results of our study indicate that further studies are warranted to investigate whether thyroid hormone perturbations play a role in the development of ASD by evaluating additional potential confounders and genotype or phenotype in larger studies.

PMID: 21882364
DOI: 10.1002/aur.219.