Wednesday, October 27, 2010

Think You Have Autism? Don't Take a Quiz.

Over in the autism area on, Lisa Jo Rudy posted something today where she talks about how taking the self-administered Autism Quotient (AQ) test might be a good first step if you think you have autism -
Of course, there is a disclaimer that these tests are not diagnostic, and they're only to be used for "genuine research." Still, for parents of children on the autism spectrum, adults wondering whether they might fall into an autism spectrum category, or anyone concerned about the symptoms of autism, these tests may be a useful first step in deciding whether or not to seek an evaluation.
This is very bad advice.

First of all, if you seriously think that you may have a disorder such as autism or any other mental disorder then you should seek professional help.  You should not try to take a test you found on the Internet to see if you might "fall into an autism spectrum category" or to give you a "hint".  None of the lists of signs symptoms on the Internet nor any of of the tests out there are going to be able to tell you whether you have autism.  Your "hint" should be that you think there is something wrong and that alone should spur you to seek a professional's opinion.

But lets say that you have decided to take Lisa's advise or that you, like many people before you, have decided that this test is an appropriate way to determine whether you have autism.   The question then becomes if you take the Autism Quotient test and score high enough, how likely are you to actually have autism?

It turns out that the answer is not very likely - the odds are about 1 in 10.

To say that the opposite way, if you had a group of ten people who all scored high (over 32), nine of them would not have autism.  So if you are claiming that you have autism based solely on a self-administered AQ test then you are most likely wrong.

To make matters worse, even if you score below that 32 number, you are still somewhat likely to have autism.  If you took a group of ten people who actually had autism, two of them would likely score below the 32 cutoff.

So either way the AQ isn't going to tell you that much.

To understand the reason the odds are so very much against you, you have to understand what the purpose of a test like the AQ is - and what it isn't.  A test like this is supposed to be used to help find people who are more likely to have a condition.  It is not supposed to be able to tell you that one specific person has the condition.

A test like this can be used as a screening tool in research to help researchers find the people who are more likely to have a condition so that they can focus on those people.  Or, if the test has been validated in earlier studies, researchers can use the results of the test to draw general conclusions about the people in their study.

In either case, to properly use the test you have to know how good of a job the test does at finding those who have a condition and eliminating those that don't.  These concepts are formally called sensitivity and specificity.  The sensitivity of a test tells you have good of a job the test does at finding the people who have the condition while the specificity tells you how good of a job the the test does at telling you which people don't have the condition.

In an ideal world, you would want every test to identify every person that has a condition (sensitivity of 100%) and exclude every person who doesn't (specificity of 100%).  But, in the real world, tests are never that accurate and we have to make do with what we can get.

When it comes the sensitivity and specificity, the AQ isn't the greatest but it isn't too bad.  According to a recent paper that I was reading, the AQ has been demonstrated to find 80% of the target group (sensitivity 80%) while only misidentifying 2% of the rest (specificity ~ 98%).

Which leads me to my next, point, what is it exactly that the AQ is supposed to be finding?  Here's a hint, it isn't what you normally think of as autism - "The Autism Spectrum Quotient (AQ) has been developed to measure the degree to which an adult with normal intelligence has autistic traits".  If you dig a little bit more, you would see that this test is meant to find adults who have "traits" of Asperger's or high-functioning autism.

Or in other words, this test is geared towards finding individuals who fall on a small portion of the autism spectrum but is not going to be very helpful in identifying the majority of people with autism.  Well, it won't be helpful  unless you believe that - all evidence to the contrary - the majority of people with autism are high functioning.

So far the AQ doesn't seem to bad - it should be capable of identifying the majority of its target audience.  But there is one last piece to the puzzle of understanding why the AQ isn't able to tell you much, and that piece is called the positive predictive value.  The idea is to take the sensitivity and specificity and put them in practical terms, and this value does that by telling you how likely it is that you have a condition if you have a positive value on the test.

This is where the AQ starts running into some serious problems - the positive predictive value is somewhere between 8% and 12%.  This means that even if you have a positive value on the test, you are only about 10% likely to have Asperger's or high-functioning autism.  The other 90% of the time the test is just wrong.

If that doesn't make any sense to you, perhaps an example would make the picture clearer.

Say you are looking at a group of 10,000 people and that we can assume that 1% of the people have any form of autism.  How many people will the AQ correctly identify, how many will it fail to identify, and how many will it falsely identify?

The first thing we need to know is how many of the cases of autism we would expect to be classified as Asperger's or high-functioning autism.  While there isn't a good answer to this question, I think it would be reasonable to assume that 25% of all of the people with autism fall into one of those two groups.  I suspect that the actual number would be less than this, but this number is good enough for this example.

So, with 10,000 people, we would expect 100 of them to have any form of autism and 25 of them to have Asperger's or high-functioning autism. Given what has been found in studies that looked at the validity of the AQ, we would expect that the AQ would correctly identity 20 of that 25 (80% sensitivity) and miss 5 out of the 25.  We would also expect that 2% of the rest of the population would be falsely identified as having Asperger's or high-functioning autism, or roughly 200 people.

If we put that all together, we would find that, out of the 220 people identified by this test, only 20 would actually be correctly identified and another 5 would be missed.  Hence the positive predictive value would be about 9.1%, which translates roughly to a 1 in 10 chance of being correctly identified.

Now, just to nitpick my own argument and be completely honest,  one possible source of error in the above analysis is what the AQ would show for the 75 other cases of autism.  Would it be able to label them as having autism or would it miss them as well?  The short answer is that we don't know because this test has never been validated in this population.  No published research has shown how well the AQ does at detecting classic autism, PDD-NOS, Retts, or CDD in a large group of people and, without that information, it is simply impossible to know how well it would perform.

But, for the sake of argument, lets assume that the AQ works the same for every person with autism rather than just the higher functioning ones.  If you use the same assumptions that I used above, you would find that a positive result in the test would give you a 1 in 3.5 chance (or about 30%) of actually having autism.

The bottom line is that even if you get a high score on the Autism Quotient you are not likely to autism.   So if you think you might have autism, don't take a random test on the Internet - go talk to a professional instead.

Saturday, October 23, 2010

The Misuse of Labels

When talking about practically any subject, we use certain words or phrases to represent another, more complex topic. If you had to fully articulate a complex subject each and every time that you wanted to talk about it, you would be unable to express any complex idea in a reasonable amount of time, which would be a bad thing (unless you are an Ent).  So these shortcut are necessary to have any sort of real conversation.

When you take this idea of shoving a series of ideas behind a single work or phrase and apply it to medicine or child development, what you get is called a label. The purpose of the label is to describe a complex condition and wrap it up in a single word that fits nicely into a sentence. That way you don't have to say a child has "impaired social interaction and communication skill, restricted and repetitive behaviors, and potential sensory issues" all of the time, you can simplify that and say that the child has autism.

But there is the problem with the labels.  They only work as long as everyone has the same idea of what they mean. If you have a group of people who start using the label to mean something else or attach their own custom meanings to the word then the entire idea breaks down and all you are left with is confusion.

Take for example the the label of "gifted" as it is applied to a child. This label is relatively straight forward and means that the child is very intelligent or talented or, as the National Association for Gifted Children puts it -
Students, children, or youth who give evidence of high achievement capability in areas such as intellectual, creative, artistic, or leadership capacity, or in specific academic fields, and who need services and activities not ordinarily provided by the school in order to fully develop those capabilities
The "gifted" label is not that complex idea. Yet there are those who take a relatively simple label and seem to feel the need to make it into something that it is not. A perfect example of this is an article published in the New Scientist called Prodigy psychologist: The gifted child's curse. From the first paragraph -
When children are labelled as "gifted" we like to think the world will be their oyster when they grow up. Be very careful, warns British psychologist Joan Freeman. As she explains to Alison George, her 35 years of studying children with extraordinary abilities has revealed that the label has as many negatives as positives
The rest of the article continues in the same vein, but what is missing from it is what is negative about the label "gifted". The psychologist being quoted describes many problems with how parents react to the label or how gifted children don't always go onto to be successful as an adult. All of these "negatives" describe how people's reaction to the label might be less than ideal or how having a certain high level of intelligence doesn't guarantee success.  But none of these negatives have to do with what the label represents - being "gifted" is not a negative.

I think the problem comes about because people are unable to separate the characteristics of a label from the person themselves. A label just describes one part of who a person is and is not meant to describe every facet  of a person.

Just because you are "gifted" does not mean that you are a hard worker or that everything is going to be easy for you. Nor does it mean that you will have the perfect parents who will provide the optimal learning experience to bring out your exact talents. These are larger issues that need to be dealt with in the context of being a person and are not explicitly tied to the idea of being gifted - you can still have these issues without being gifted and being gifted does not mean you will have these issues.

On the flip side, you have a label like autism where people try and take what are mostly negative attributes and make it into a positive. When you look at what goes into the label of autism, you will find a set of characteristics that everyone can have little bits and pieces of but, in autism, are taken to unhealthy extremes.  That is what the label autism means - there are issues with communication, social, and restricted interests that are severe enough to cause major problems.  None of the attributes that go along with the label "autism" are a good thing.

But just because you have a label of autism does not mean that you are just a set of negative characteristics- there is much more to a person that just a label of autism.  A person with autism can be smart, funny, loving, caring, or any of the other traits that can apply to any other person.  The autism label just describes one small part of who a person is.

However, there are a small number of people who are attempting to hijack the autism label and make it mean something completely different.  Perhaps the best known of this group are the "aspies" who are trying to turn the label Asperger's into something that it is not. Lets be clear here, the Asperger's label is part of what is know as the autism spectrum and, as such, is a form of autism.  But if you listen to what these aspies have to say, they will tell you that Asperger's is not autism.  They will tell you that Asperger's is about being highly intelligent, dispassionate, and being neurodiverse.

But that is not what the label of Asperger's means.  Having Asperger's does not means you are automatically intelligent or dispassionate and not everyone who is technologically proficient and social awkward has Asperger's. You can still be intelligent and have Asperger's but one does not means the other.

You may think this entire discussion is moot and pointless but I think it matters a great deal. As I have talked about in the past, many of those seeking to turn the label of autism into something that it is not are doing so on the backs of those who are more disabled.

The end result of this hijacking of the autism label is you have people like Ari Ne'eman talking about how "autistic people" don't want to be cured, or Michael John Carley saying that they find the idea of being lumped in with lower functioning people with autism "hard to shallow" because they sometimes have to wear adult diapers, or Hannah Fjeldsted saying it would be "an insult and a mockeryto be lumped in with the lower functioning because aspies have their pride to think about.

And this insanity is not only limited to fringe people like this, it is slowly spreading to more reputable places like WebMD -
Some traits that are typical of Asperger's syndrome, such as attention to detail and focused interests, can increase chances of university and career success. Many people with Asperger's seem to be fascinated with technology, and a common career choice is engineering. But scientific careers are by no means the only areas where people with Asperger's excel. Indeed, many respected historical figures have had symptoms of Asperger's, including Wolfgang Amadeus Mozart, Albert Einstein, Marie Curie, and Thomas Jefferson.
There are so many things wrong with the paragraph it isn't even funny. People with Asperger's aren't focused on details, they are obsessed with certain specific ones and not in a good way (Restricted repetitive and stereotyped patterns of behavior, interests, and activities anyone?). Nor is there an automatic relationship between technology and Asperger's - that is a myth. And don't even get me started on the absurdity of saying that historical figures could have had Asperger's because of certain characteristics that appear in writings about them.  All of the labels are based on a set of characteristics that appear to a greater or lesser extent in all people but having some similar characteristics does not mean you have "symptoms of Asperger's".

I have no idea when this nonsense starting appearing on WebMD but it certainly is evidence that the attempted re-branding of Asperger's and, by correlation, autism is taking hold. Unfortunately, these ideas create an image of autism that those who are more severely affected will never be able to live up to.  Maybe the solution is to remove the Asperger's label from the rest of the spectrum and let the aspies redefine it to mean what ever they think it means this week.

But regardless, the point is that when using a label you have to use it correctly.  You have to be able to separate out the characteristics that it implies from the person as a whole. Each and every person is much more than the sum of their labels and just because a person has a specific label does not mean that they are limited to being just the label. A person is a person, not a label.

Wednesday, October 20, 2010

Jaundice And Autism

Earlier this month, a study was published in Pediatrics that suggested that there might be a relationship between neonatal jaundice and autism.  After reading the study several times, I think I can best sum it up as a little weak and very confusing.

In this study, researchers examined the electronic health records of at all 733,826 children born in Denmark between 1994 and 2004 and collected data on a variety of factors.  These factors not only included whether the child had jaundice or one of several developmental disorders but also included data on their birth weight, gestational age, fetal presentation, apgar score, demographic information about the parents, and other factors.  Or, in short, they collected a lot of data.

The researchers found that almost 5% of the children in the study had a diagnosis of neonatal jaundice noted in their medical records.  As would be expected, these children were more likely to be born premature (36 weeks or earlier) by a margin of 43% to 4.4%, more likely to be underweight - 53% to 14%, and more likely to have an irregular fetal presentation - 29% to 17%.  I don't know if any of these relationships are statistically significant as the study does not say, but I don't think that really matters as none of these relationships are controversial.

Moving onto the autism side of things, the study found a total of 1,721 children who had a diagnosis "in the spectrum of disorders of psychological development".  This spectrum included disorders of speech, motor, and social development as well as autism and intellectual disability (ID).  In this group, there were 577 children that had a diagnosis that put them on the autism spectrum and 1,239 children that had intellectual disability.  There were 74 children in this group that had both intellectual disability and autism.

The researchers crunched the numbers and found some rather peculiar results.  Jaundice was found to be associated with autism but only in full term infants.  To make matters more confusing, this association partially disappeared when the children were separated out by the time of year that they were born (summer vs winter) and whether they were first born or not.  Children with jaundice who were born in the summer or who were first born did not have an increased risk of autism, while children born in the winter or were not first born did.

As I said, I find this result to be rather confusing.

The lack of association between jaundice and autism in premature children is odd.  Children with jaundice are much more likely to be premature and premature children are more likely to have autism.  The numbers found in this study bear that out - 43% of the children with jaundice were premature and prematurity is more common in the children with autism (7.8%) than the general population (6.3%, 4.4% in those without jaundice).  Intuitively it seems like there should have been a relation there, but there wasn't.

The authors try and explain away the time year effect by exposure to sunlight and hence vitamin D levels, but, while that sounds good, there is no demonstrated correlation between vitamin D and autism.  Similarly, they try to explain the order of birth effect by differences in hospital discharge policies and maternal antibodies in second and later pregnancies.  I don't find any of these reasons convincing as I like to see actual data behind assertions rather than just magical thinking.  Although, to be fair, some studies have hinted that there might be a seasonal bias with autism.

I have to question how significant the association found is.  It is one thing to say that there is an increased risk but the actual significance of the association rests on the count of cases.  So I would have liked to see the actual number of children who had autism and jaundice but the only figures provided are hazard ratios (HR).

Not to get too technical, but this hazard ratio, which is basically a relative risk, provides an estimate of how much higher the (relative) risk of the outcome (autism in this case) is if the child had exposure to what was being measured (jaundice) when compared to those who were not.  So in this case, an HR of 1 would mean equal risk while an HR of 2 would mean that the children with jaundice were twice as likely to have autism than the children who didn't have autism.

The overall unadjusted HR for all children with autism was found to be 1.84 while that number dropped to 1.56 after being adjusted for maternal smoking, apgar scores, mother's citizenship, birth weight, and congenital malformations.  So we aren't talking about a large increase of risk.  But perhaps more telling is the ranges of these values.

At the risk of getting a bit technical again, the study says that the 95% confidence intervals for these figures are 1.05 to 2.69 and 1.05 to 2.30, respectively.  This confidence interval basically means that we would be 95% certain that the "real" value of the HR would be between these values.  These values represent a rather large range - from no increased risk to about 2.5 times the risk - which suggests that the increased risk are based on relatively few cases.  A result based on a fewer cases or, more appropriately, on a a small difference in the relative number of cases, would be weaker than a result based on a larger number of cases or a larger difference.

A crude example here would be if the unexposed group had 1 case in a group of 10 while the exposed group had 2 cases in a group of ten.  In theory, the exposure group would have twice the risk but in practice that risk could shift drastically if you looked at a larger sample.

And, speaking of relatively few cases, consider the total number of children with autism in the study.  In ten years only 577 children with autism were born in Denmark?  That would equate to a rate of about 7.8 per 10,000 which is extremely low when compared to the 91 per 10,000 recently found in this country.  This isn't data from the 80s or early 90s when you would expect to see this rate of autism, this data was from the late 90s and almost halfway through the 2000's.  It it possible that the 577 number would increase over time as the children aged (the youngest children in the study would have only been a little over 3 when the data was collected), but still, if you considered all of the children found to have a disability included in this study, we are still only talking about 23.5 per 10,000.

Either there are simply fewer cases in this country or the majority of children with autism have been missed.  If it is the first reason, then I would have to wonder at how applicable these results would be the world and, more importantly, why researchers aren't trying to figure out what is different about this country.  If it is second, then the association found would likely be flawed as well.

So, as I said at the beginning, the results from this study are confusing.  If I had to guess, I would think that the association found wasn't real, but that is just my opinion.  The only way to know for certain would be to do more studies.


Maimburg RD, Bech BH, Væth M, Møller-Madsen B, Olsen J. Neonatal Jaundice, Autism, and Other Disorders of Psychological Development. Pediatrics. 2010 Oct 11. [Epub ahead of print] PubMed PMID: 20937652. doi: 10.1542/peds.2010-0052

Sunday, October 17, 2010


Today was a good day.

The day started off well, with the children sleeping through the night until their typical wake up time of about 6 AM. Twin B came in first this morning, which is a bit unusual, and asked for the TV to be turned on.  We managed to put her off for about a half hour before we gave in and turned it on for her.

You see, Twin B has this thing were she has to have constant noise (preferably electronic) in the background and she has this other thing with the word "no".  For the past few months, whenever you tell her "no" she immediately goes into full meltdown mode and tantrums for the next twenty to thirty minutes.  When you combine denying her one of her "stims" plus the word "no" you get a somewhat volatile situation.

Fortunately, we managed to avoid the meltdown this morning after using the dreaded "no" word and only had some minor crying off and on for the next 25 minutes before she finally calmed down enough that we could give her want she wanted.  In our world, this is called progress.

You might ask yourself why we would risk a meltdown at 5:30 in the morning (when we were still sleeping), and the answer is simple.  My daughter has autism and we have to do everything possible to help her get past it.  We don't have the choice of trying to help her get past the problems some of the time and not others - consistency is one of the keys to overcoming the obsessions of autism.  And before you say that it doesn't matter, it does.  She has to be able to accept the someone telling her "no" and she can't assume that every if there is a TV in the same room as her that it will be on.  She has to be able to function in the world even if it isn't exactly to her liking.

The rest of the morning was fairly uneventful, with only a few hiccups.  The twins did their typical trick of only grazing on  breakfast while Baby C showed some (cough, cough) "spirit" in an attempt to get my cup of coffee.  For some reason, she really likes coffee but, while that isn't too bad, dealing with a three year old strung out of coffee isn't my idea of a fun morning.  I let her have a few sips before cutting her off and being treated to her trademark "try again".

That last bit takes a little explaining.  While my youngest is higher functioning than her older sisters, she is still somewhat limited in her ability to communicate and much of her speech is scripted.  She tends to reuse phrases that she has heard other people use, although she does use them in an appropriate manner.  Since she has heard the "try again" many times from her therapists when she gives an incorrect response, she has decided that that is the appropriate way to answer us when we give her an answer that she doesn't like.

So when I say "no more coffee", she replies with "try again".

It might not be the typical parent/child interaction, but hey, its communication.

A little later on in the morning, Twin A started getting upset for some reason.  It took about fifteen minutes and a small tantrum before my wife's mind reading abilities kicked in and she was able to figure out what was wrong -  the child was bored and wanted something to do.  So we got out the paints and some other art supplies and let her go to town.  Problem solved (except I am going to have to clean the paint off the walls later on tonight).

You might ask why Twin A didn't just ask to paint, and the reason is again simple.  While the twins definitely have the basic communication skills to ask for something when they know what they want, they aren't to the point yet were they are able to express an abstract though or idea such as "I want to do something but I don't know what".  Hence the agitation and the small tantrum.  Irresistible desire to express, meet (almost) immovable communication block known as my daughter's form of autism.

After lunch came the highlight of the day.  We took an outing as a family to not one but two novel places.

First we went to a fish store to buy some supplies for the fish tank and to let the kids look at the fish - they all love fish (no idea why).  That part of the trip went relatively smoothly with only a few bumps transitioning into the store.  The twins were a little stressed by the new environment - we could tell because they were walking around with their hands over their ears - but soon enough they were jumping and waving their arms in front of the fish tanks.

As an aside, if you have never seen two children jumping and hopping through a store while holding their hands over their ears and flapping their elbows, you have to see it.  While most of the people in the store glared and seemed to want to say "what is wrong with those children", we have to laugh because of how much fun they are having and how cute they look.  Besides, it wasn't all that long ago that they refused to even walk on their own while out in public, so hopping is progress.

Anyway, we stayed in the store for a good fifteen minutes before we noticed the tell-tale signs of increasing agitation and took that as our cue that it was time to go.  It got a bit touchy as Twin A wasn't quite ready to leave but her sisters were more than ready.  As we headed to the door, she did her typical bit of dropping to the ground and shouting and I had to resort to picking her up and carrying her out of the store.

The second trip was to a restaurant that we had never been to before.  It is very hard to find any restaurant that not only has food that the twins can have - they have food intolerances - but that also has food that they are willing to eat.  They are picky eaters and are adverse to trying anything new (yet another thing that we are working on).

Baby C is easier because she does not have any food intolerances and she is typically happy to try new food.  However, today she decided that she wanted nothing to do with new food or with a new restaurant and felt the need to share her displeasure with the entire restaurant.  She started crying the minute that we were seated and finally managed to calm down shortly after we placed our orders.  After that, the rest of the meal went well and, much to our surprise, the twins actually ate what we ordered for them.

After the restaurant we even managed to take a short walk around town before returning to the car and returning home.  I guess that actually make three novel environments for the kids today - a new family record.

As I said, today was a good day.  Today we helped our daughters deal with their obsessions, communicate a little better, and cope with the stress of the unknown.  Or, in short, today we helped them overcome just a little bit more of their autism.

Today we all had a good day and enjoyed ourselves in the process.

But today was not a day without autism.  I don't know if we will ever again have a day without autism.  Almost every single thing that we did today was carefully laid out and planned with autism firmly in mind.  With three children on the spectrum, we do not have the luxury of ever forgetting for a moment that our children have special needs because if we do, the day will not go so well.

But such is the life of an autism parent.  As much as I wish that my children did not have to struggle with autism they do, and there is nothing that I can do to change that fact.    My children have autism and I, like many other autism parents, will do whatever it takes to help our children get past the difficulties that autism can cause.  We will give up our ambitions and goals and completely change our lives in the hope of making a better future for our children.  We do this not because we are trying to make our children into something that they are not but rather because we want them to have the best chance possible of overcoming their autism.

By now, you must be wondering what the point of this entire post is, so here it is.

Being an autism parent can be a tough - and sometimes thankless - job, far more so than being a parent to a "typical" child.  If you are lucky, your efforts will be rewarded when your child is able to function on their own in spite of having a disability like autism.  If you aren't, then you worry about who will take care of your children once you are no longer able.

As I said, it is what it is.  But, given all of that, there are people out there who seem hell bent on making our job harder.  I am talking about people like Suvi-Tuuli Allan who don't seem to know what they are talking about and say things like this -
@TannersDad: We can save more children if we cure the parents. #autism
and this -
@TannersDad: I was being sarcastic. WTF is a profound autism anyways?
and this -
Finding a cure for #autism is all about parents trying to make their kids "normal" so they can be proud of their productive little NT kids.
The first time I ran across people like this,  I was flabbergasted.  Lately, I have just been getting annoyed with their ignorance.  So let me just make this simple for all of the children like Ms. Allan who seem to think that they understand exactly what being an autism parent is like.

Shut up until you manage to grow up and learn what the hell you are talking about.

Sunday, October 10, 2010

A Critical Look at Social Demographic Change and Autism

Last week I wrote a somewhat critical post about a paper entitled "Social Demographic Change and Autism"1.  I suggested that calling a conclusion based on estimated data a "major discovery" might not be warranted.

My primary objection at the time was that if you are basing a conclusion on the differences between identical and fraternal twins that perhaps you should be able to tell which twins are identical and which are fraternal. However, a commenter suggested that perhaps I was being a little too hard on the study, so I spent a little bit of time and gathered some data to see if I had the right or wrong idea.  After taking a closer look, I think I had the right idea and I am going to explain why below.

The paper in question used data from the California Department of Developmental Services (DDS) to support the following three conclusions -
First, the estimated heritability of autism has been dramatically overstated. Second, heritability estimates can change over remarkably short periods of time because of increases in germ cell mutations. Third, social demographic change can yield genetic changes that, at the population level, combine to contribute to the increased prevalence of autism.
These conclusions are based on two primary observations from the data.

The first observation is that the generally accepted concordance rates of autism in twins are wrong and that there is not a large difference between in concordance between identical and fraternal twins.  The second observation is that as the average parental age went up that the concordance among all same sex twins went up as the concordance among opposite sex twins went down.  The authors then use these facts to suggest that there is a relationship between parental age and de novo mutations, specifically copy number variations, that could explain these facts. They conclude that increasing parental age could be a large factor in the increased prevalence of autism.

After reading the paper a few times and spending some time gathering and analyzing data, it is my opinion that the data in the paper do not support the conclusions.  I am going to start with the idea that copy number variations (CNVs) can lead to an increased risks of autism and work backwards from there.

The first problem I see is that this paper has no direct measurement of any CNVs in the children with autism nor any data showing that they are more common in the older parents included in this study.  While in general I would agree that other research has shown that CNVs can vary as a function of parental age, it does not follow that that the specific children included in this study had an unusual amount of CNVs or that these CNVs played a causal role in causing these children's autism.

There have been a large number of studies in the recent past that have looked for CNVs in children with autism and the overall conclusions are mixed.  On one hand, you have studies2 that actually looked for CNVs in a sizable group of children with autism and found significant ones in only 7% of the population and on the other3 you have studies that found that CNVs as a whole aren't more common in children with autism, just "rare" ones are.  In both cases, the majority of the child had their own (almost) unique mutations that were specific to them and not shared by other children.

So this begs the question of how can these CNVs can be responsible for the increased risk of autism?  Even if we accept the facts that they are more common in children with autism and become more common as the parents get older, how can a large number of almost unique mutations lead to the same condition?  You can't simply suggest that CNVs are the reason, there has to be an actual process that goes from the CNV to a diagnosis of autism.  The paper suggests no such mechanism.

As an aside, CNVs have also been found in other, possibly related, conditions such as schizophrenia4 and ADHD.  In one recent study5, CNVs were found in 16% of children with ADHD but were also found in 8% of the typical controls.  Based on results like this, I have to wonder how common CNVs are in the general population and how much autism-specific risk can be assigned to an arbitrary CNV.

The next problem with CNVs is the presumed relationship between the type of twin and the presence or absence of a CNV -
Recall that because MZ twins are developed from a single pair of matched egg and sperm cells, any de novo mutations will be found in both twins. In contrast, DZ twins develop from two distinct pairs of egg and sperm cells. Because de novo mutations are rare events, the chance that both DZ twins will share the same de novo mutation is extremely low.
The problem with this presumption is that is isn't necessarily true - identical twins do not always share the same CNV.  While this idea seems counterintuitive, it has been demonstrated by studies6 and I have personally seen this result (my identical twin daughters have different CNVs).  I don't have any hard facts on the flip side of the relationship, that fraternal twins are unlikely to share CNVs, but I have some doubts that that statement is true.

The argument here would come down to what is causing the CNV and when these mutations occur.  The authors assume that CNVs are present in parents' egg or sperm but I am not sure that is always the case.  If identical twins can have different CNVs then that implies that mutations can happen after fertilization which means that the mutations are not always in the parent's genetic material.  And if that is the case, then it should be possible for fraternal twins to both have their own CNVs.  The question would just be how often this happens, but I have not seen any studies that looked specifically at this issue.

When you combine the above problems with the fact that there is no direct data on the actual CNVs in the paper, I would suggest that the conclusion that suggests older parents have move CNVs which in turn caused more autism might not be supportable.

Next,  lets look at the twin specific findings of this paper.  Before I get into the details, I wanted to talk a little bit about the properties of the different types of twins.  For the purposes of this discussion, I am going to talk in generalities and gloss over some of the rare types of twins and higher order multiples as these will just confuse the issue.  Just be aware that the discussion below isn't the entire picture when it comes to multiple births.

Identical, or monozygotic (MZ), twins are the result of a single fertilized egg splitting into two parts.  MZ twins are basically a random event and the rate of MZ twinning does not vary by region, race, maternal age, fertility treatments, or time period.  MZ twins are not hereditary and cannot be "passed down" through generations.  The rate of MZ twinning is basically a constant worldwide and has been for the measurable past7 - about 1 in 250 pregnancies.

Fraternal, or dizygotic (DZ), twins are the result of multiple eggs being fertilized at once or, as is more common as of late, fertility treatments.  The rate of DZ twinning does vary by region, race, maternal age, fertility treatments, and time periods.  Natural DZ twinning is hereditary and can be passed down to children (although it is the mother's family history that matters, not the father's).  The rate of DZ twinning is not a constant and changes over time and the number of DZ twins have been growing rather rapidly since the 1980s

All types of twins have a substantially greater risk for having prenatal complications or for being born premature than do non-twins8.  MZ twins are more likely than DZ twins to have complications because they are more likely to share resources, such as the placenta, in the womb.  Also, there are certain prenatal complications that are only happen to MZ twins, such as twin-to-twin transfusion syndrome.

It has been demonstrated that prematurity and other prenatal complications come with an increased risk of autism, so while I don't have any exact figures I think it safe to say that twins of all types would run a greater chance of having autism than non-twins.  I would also suggest that MZ twins could have a greater risk of autism than DZ twins if only because of their increased prenatal risks.  (Although as a side note, I would also ague for an increased risk based on the fact that they would be more likely to share the same genetic and environmental vulnerabilities that might lead to autism).

So, back to the paper.  As I talked about last week, the data in this paper does not distinguish between identical and fraternal twins, so to arrive at the breakdown between the different types of twins the authors had to estimate.  The estimate that they used was based on the facts that all opposite sex twins are DZ twins and that the chance of a set of DZ twins being the opposite sex are the same as them being the same sex.  Based on those assumptions and data about the total number of twin births in California,  they arrived at the result that 55% of all of the same sex twins in the paper's data were MZ twins.

There are a few problems with this method of estimating.

Lets start with the fact that the proportion of same sex twins that are MZ twins is not a constant and changes significantly even over the study period (1992 to 2000).  To show this, I used national birth data from a few different sources as well as birth data from California from the CDC9, 10, 11.  The following are estimates based on the total number of twins born, the number of births per year, and the fact that MZ twins occur at a constant rate of about 1 in 250.

First, lets look at the breakdown of twin births in the US from 1980 to 2000.  As you can see from the chart below, the overall number of sets of twins has been growing rapidly but most of this growth comes from an increased number of DZ and not MZ twins.

Second, consider the following California specific twin data.  While I could only find complete birth data from 1995 onwards, I believe this data is sufficient to show the skewing in the proportion of twins.  For the following chart, I used the authors' figure for identical twinning in California (4.4 per 1,000) which is slightly higher than the accepted figure (1 in 250).  As you can see, the number of DZ twins increased every year while the number of MZ twins decrease slightly as the general birth date decreased.

I also replicated the calculation for the percentage of same sex twins that are identical and that is labeled R in the chart below.  As you an see, from 1995 to 2000 the value for R changed from 55.4% to 49.5%.  As a side note, if you take the rate of MZ twins to be slightly lower (1 in 250), the value for R changes from  51.7% in 1995 to 46% in 2000.  Or in other words, this proportion is very highly sensitive to the actual breakdown of twins and is quite volatile.

The third problem is that the distribution of twins by parental age is also changing over the study period.  In general, the total number of births in California from 1995 to 2000 fell but the average age of the mother was going up.  This increase in the maternal age was mostly caused by younger women having less children and older women having more.  For example, in 1995 there were 478,125 children born to mothers under 35 while 73,920 were born to mothers 35 and older but by 2000, the under 35 crowd had decreased to 446,594 while the older mothers increased to 85,365.

Now, the authors acknowledged this general shift in maternal age in the paper and talked about it.   However, what they left out was that the average age for mothers of twins was also going up at the same time and that it was rising faster.

The difference between these two lines are all DZ twins.  Remember, the chance of having MZ twins does not vary by age but the chance of DZ twins does (older age leads to a higher risk of DZ twins).  As a result, the age of the mothers of MZ twins can only increase the same amount as all mothers, not more as is shown in the chart above.

As a result, not only does the relationship between the number of MZ and DZ twins change with time, it also changes with the mother's age.  When you look at mothers older than 35, they will have more DZ twins and proportionately less MZ twins (lower R) than do mothers that are younger.

There are other potential biases other than the ones above, such as race.  I did not take the time to chart these as I think the general idea is clear - the relationship between the number of DZ and MZ twins is not simple and cannot be represented as a single number over any significant length of time.

When you combine the above problems you can see that getting the breakdown between MZ and DZ twins is not a simple thing and is related to several factors.  None of these factors were controlled for in the study.

Now ignore all of that for the moment and consider the twins that were included in the study.  Out of the 56,631 sets of twins born in California between 1992 and 2000, only 503 were included - less than 1% of all of the twins.  The authors make the assumption that relationships that hold for the entire population will also hold for this specific subset.  If this selection of twins were random, I would agree that the relationships should hold.

But, we are not talking about a random selection, we are talking about a very specific selection - twins were at least one twin had a diagnosis of autism - and that is not a random process.  If all types of twin were at the same risk and had the same relation to the other risk factors for autism then the relationship might hold.  But we know that the prevalence of autism varies by race, parental age, and with prenatal complications and we know that the breakdown of twins vary by these factors as well.  As a result, I think that even if the R value that the authors calculated from the entire population was a valid number, it would not necessarily apply to the group of twins included in the study.

The only way to get at the actual breakdown of twins would have been to do an actual count of the different types of twins.  Without this breakdown, one of the major points of the paper - the idea that the heritability of autism is overstated - is completely unsupported by the data.

As a further blow to this conclusion, consider that the authors only included data for twins that both had a diagnosis of autism - not Asperger's, CDD, Retts, or even PDD-NOS.  So if one twin had a diagnosis of autism and the other had PDD-NOS, they would have been counted as non-concordant.  But as has been shown elsewhere12, twins - even identical ones - are not always concordant for severity.  There are many twins were one has diagnosis of autism and the other with PDD-NOS, or one is autism and the other is Asperger's.  As a result, the current paper would likely underestimate the concordance for all types of twins.

But lets assume that none of the above applies and that all twins have the identical risk of having at least one twin with autism, that the relationship between MZ and DZ twins is a constant for the study period, and that said relationship could be used for the study population without an issue.  There would still be a problem with the breakdown because the concordance of the different types of twins was determined using a "simple linear transformation".  That can't work unless you are already assuming that MZ and DZ twins should have a similar breakdown.

Let me give an example.  Assume that you have 10 sets of male-male twins of and that you know that 6 of them both have autism.  Further assume that you know that 5 of the twins are MZ and 5 are DZ.  If you use a simple linear breakdown based on the fact that 50% of the twins are MZ, you could conclude that 3 of the 5 are MZ twins that both have autism and 3 of the 5 are DZ twins that both have autism.   But given the same data,  you could just as easily concluded that 4 of 5 MZ twins have autism while only 1 of 5 DZ twins do, or anything in between.  The difference in the concordance rates would be significant - 60% for both MZ and DZ in the first and 80% for MZ and 20% for DZ in the second.  I am not saying that the paper used this exact simple split, but it wasn't much more complex than that.

The point is that a linear transformation is going to skew the results if there is a grouping with low concordance combined with a group of high concordance.  The lower group would appear to be much higher that it should be while the higher group would appear to be much lower.

That last point is probably the most important because that is exactly what this paper showed - that DZ have a higher concordance than previously thought and MZ have a much lower concordance.  The authors are claiming this result even though almost every other paper on this subject has found something different - that DZ twins have a much lower concordance than do MZ twins.  So, I would have to conclude that the breakdown of the data in this study is flawed.  Especially considering the fact that the other studies on the subject12 were able to properly split out MZ and DZ twins.

As for the last idea about parental age being associated with a greater risk of autism in same sex twins, that could be explained by other factors.  And when it comes down to the numbers, the increase in the average age is rather small (1.5 years, from 30.6 to 32) and only slightly larger than the general increase in maternal age across all children.

As I mentioned above, older mothers in California were becoming more common among all children and especially for DZ twins.  In the general population in California, the average maternal age from 1995 to 2000 went from approximately 27.2 to 27.8 while in mothers of twins it went from 29 to 30.  So is an increase in parental age of 1.5 years significant when the population as a whole is showing about the same increase?

The other thing I would point out, and this may just be me nitpicking, is that the authors knew that the specific data set they used had already been used to establish a relationship between parental age and risk of autism.  One the first page of the paper, the authors talk about how another study found a relationship between parental age and autism and acknowledge that the other study used the same data set as they did.  I don't think it can be considered a surprise (or major discovery) if you find a relationship that others have already shown in the same data set.

Whew.  If you have managed to read all the way down to here, I have to commend you.  You will be receiving a gold jabberwocky sticker as a reward.  Now, to wrap this all up.

It is my opinion that the conclusions of the paper aren't supported by the data that is in the study.  The breakdown between identical and non-identical twins is likely flawed, the association with parental age could be an artifact of a general trend in the data, the specific type of mutations (CNVs) are relatively rare and unique even when seen in people with autism, and there is no known mechanism for these disparate CNVs to all lead to autism.

All this is not to say that the entire paper is worthless.  I actually found this paper to be very interesting.  I believe it is likely that a social demographic change could account for some of the increase in autism prevalence and I would agree that the wrong conclusion has been drawn from earlier twin studies.  Also, the raw data that is published in the paper actually fits in quite nicely with the data from other recent studies and helps fill out the overall picture (that is a subject for another time).

But, my beliefs about the ideas in the paper notwithstanding, I don't think that the conclusions of this paper are supported by the data included.


1. Liu, K., Zerubavel, N., & Bearman, P. (2010). Social demographic change and autism. Demography, 47(2), 327-43. Retrieved from

2. Shen, Y., Dies, K. A., Holm, I. A., Bridgemohan, C., Sobeih, M. M., Caronna, E. B., et al. (2010). Clinical Genetic Testing for Patients With Autism Spectrum Disorders. Pediatrics. doi: 10.1542/peds.2009-1684.

3. Pinto, D., Pagnamenta, A. T., Klei, L., Anney, R., Merico, D., Regan, R., et al. (2010). Functional impact of global rare copy number variation in autism spectrum disorders. Nature, 1-5. Nature Publishing Group. doi: 10.1038/nature09146.


5. Williams, N. M., Zaharieva, I., Martin, A., Langley, K., Mantripragada, K., Fossdal, R., et al. (2010). Rare chromosomal deletions and duplications in attention-deficit hyperactivity disorder: a genome-wide analysis. The Lancet. doi: 10.1016/S0140-6736(10)61109-9.

6. Bruder, C. E., Piotrowski, A., Gijsbers, A. A., Andersson, R., Erickson, S., de Ståhl, T. D., et al. (2008). Phenotypically concordant and discordant monozygotic twins display different DNA copy-number-variation profiles. American journal of human genetics, 82(3), 763-71. doi: 10.1016/j.ajhg.2007.12.011.

7. Bortolus, R., Parazzini, F., Chatenoud, L., Benzi, G., Bianchi, M. M., Marini, a., et al. (1999). The epidemiology of multiple births. Human reproduction update, 5(2), 179-87. Retrieved from

8. Deutsches Aerzteblatt International (2010, October 8). Risks in multiple pregnancies. ScienceDaily. Retrieved October 9, 2010, from

9. Martin, J. a., & Park, M. M. (1999). Trends in twin and triplet births: 1980-97. National vital statistics reports : from the Centers for Disease Control and Prevention, National Center for Health Statistics, National Vital Statistics System, 47(24), 1-16. Retrieved from


11. United States Department of Health and Human Services (US DHHS), Centers for Disease Control and Prevention (CDC), National Center for Health Statistics (NCHS), Division of Vital Statistics, Natality public-use data 1995-2002, on CDC WONDER On-line Database, November 2005. Accessed at on Oct 8, 2010

12. Rosenberg, R. E., Law, J. K., Yenokyan, G., McGready, J., Kaufmann, W. E., Law, P. A., et al. (2009). Characteristics and concordance of autism spectrum disorders among 277 twin pairs. Archives of pediatrics & adolescent medicine, 163(10), 907-14. doi: 10.1001/archpediatrics.2009.98.

Thursday, October 7, 2010

Bruesewitz v. Wyeth : Amicus Timor

As I talked about earlier this week, the US Supreme Court is going to hear arguments in Bruesewitz v. Wyeth next week. This case has to do with whether vaccine manufacturers are directly liable for damages cause by their products.

The issues in the case aren't really about vaccines, the vaccine program in this country, or even autism but rather center on what the National Childhood Vaccine Injury Act of 1986 was meant to do. Was the intent of Congress to protect vaccine manufacturers from virtually all claims of defects or wasn't it?

But, that hasn't stopped certain parties from filing a friend of the court brief with the Supreme Court saying that overturning the status quo would lead to massive harm to the country, the return of all of the banished childhood diseases, and cause puppies everywhere to spontaneously jump of the nearest bridge.

OK, I made that last one up, but the brief is full of fear, uncertainty, and doubt. It has nothing to do with the legal issues at hand and everything to do with making the justices fearful of upsetting the status quo.  You don't even need to read the entire brief to get the point, the titles of the sections are quite enough to get the point across -

I. Vaccine Development Is One Of The Greatest Public Health Achievements Of The Twentieth Century

II. Congress Enacted The Vaccine Act To Provide Adequate Compensation To Children Injured By Vaccines And To Safeguard The Nation’S Vaccine Supply

A. The Costs Of Vaccine-Related Litigation Had Threatened To Halt Vaccine Production In The United States

B. The Tort System Had Failed To Provide Adequate Compensation For Children Injured By Vaccines

C. The Vaccine Act Provides Adequate Compensation To Children Injured By Vaccines And Ensures The Stability Of The Vaccine Market And The Nation’S Vaccine Supply

III. Petitioners’ Interpretation Of The Vaccine Act Poses A Threat To The Future Production And Development Of Vaccines

A. Unpredictable Litigation Costs Could Once Again Force Vaccine Manufacturers To Abandon Or Consider Abandoning The Vaccine Market

B. The Progress That Has Been Made In Vaccine Development Since The Passage Of The Vaccine Act Could Come To A Halt

It really is a shame that the American Academy of Pediatrics and twenty one other medical organizations are so threatened by possible change that they feel the need to resort to sowing fear.  I expected better from them.

Wednesday, October 6, 2010

Jabberwocky Of The Day : Estimates Are Not Major Discoveries

Earlier this year, a paper was released entitled "Social Demographic Change And Autism" that attempted to explain the part of the rise in the rate of autism.  The authors arrived at three "major discoveries" that were supposed to change our thinking about autism.

While the ideas in the paper have some merit, I can't resist pointing out one of the flaws in one of the "major discoveries".  The discovery that I am talking about is this one -
First, the estimated heritability of autism has been dramatically overstated.
In very rough terms, this statement is basically saying that autism is not something that your parent's pass down to you but rather something that is caused by something else.  The paper goes into some specific about what this could be, but I am going to focus on this one point for now.

To prove this point, the researchers analyzed some data  -
To anticipate the main results of this article, we first demonstrate that autism heritability — defined in the narrow sense as the difference in concordance for autism between monozygotic (MZ) and dizygotic (DZ) twins is not as significant as typically believed.
Of course, it always comes back to twins.  Most other studies have shown that identical twins are more than twice as likely as fraternal twins to both have a form of autism.   But here, the researchers are basically saying that this is not true - that identical twins are not much more likely to both have autism than fraternal twins.

If this result were true, it would signal a a major change in how we think about autism.  But, as I was looking through the paper to see what numbers that the authors arrived at, I ran across this statement -
The administrative data we work with do not have a direct measure of zygosity, so we do not know from these data whether twins are MZ or DZ, which is central to the estimation of genetic influence.
Wait, what?

One of the major findings of the paper is based on the difference between identical and fraternal twins but the data in the study does not have the ability to tell you which twins are identical and which aren't?  So, how can any conclusion be reached about the differences between the two groups when you don't know what the groups are?
A simple and well-established rule that has been shown to give robust zygosity estimates has been developed for this purpose and has been widely used in research on twinning rates and a range of other research questions.
So one of the "major discoveries" of the paper - one that disagrees with most other twin studies out there - is not based on actual data but a guess of what the data might look like?

It is a good thing that the proportion of twins that are identical is a constant (oh wait, it isn't) and that factors influencing twin births weren't changing drastically during the study period (oops, they were) and that we know that identical twins aren't more likely than fraternal twins to have autism in the first place (no clue).

There are so many unknowns and possible other factors involved that without this one little, tiny yet fundamental piece of information - whether a set of twins were identical or fraternal - the conclusion based on that data becomes nothing more than a educated guess.

Conclusions should be based on data, not guesses.

Tuesday, October 5, 2010

Bruesewitz v. Wyeth : Coming Next Week

Flickr Photo by dbking
A week from today, the US Supreme Court is going to hear arguments in Bruesewitz v. Wyeth, a case about vaccine injury. At issue in this case is whether vaccine manufacturers can be directly sued in a normal court for injuries that are caused by their products.

In you are interested in the details of the case or actual filing in the case, I recommend this excellent resource which is maintained by SCOTUS blog.

As matters stand now, almost all claims of vaccine injuries must be filed with the National Vaccine Injury Compensation Program, more commonly known as vaccine court. This is a special venue that was created by the National Childhood Vaccine Injury Act of 1986 and was meant to be a no-fault, swift, flexible, and less adversarial alternative to the traditional court system. But this venue is not a the traditional court system and the rules it operates under can be quite different.

When you submit a claim with this program, the vaccine manufacturer is not the defendant (or respondent) but rather the federal government. And if you win your claim, it is not the vaccine manufacturers that pays for the damages but rather other people like you. Let me explain that last part as it can be a little confusing.  Every time a vaccine is administered, a surcharge is added to the cost of the vaccine and is paid by whoever is paying the medical bill (such as an insurance company). These surcharges are then collected by the government and any awards made by the vaccine compensation program are paid using these funds.

Or to put this in simple terms, a vaccine manufacturer cannot be sued for harm caused by their product nor are they financially liable for damages. Regardless of where you stand on the possible link between autism and vaccines, I think we can all agree that absolving an entire industry of liability is not the best of ideas and is just asking for problems.

There might have been valid reasons for setting up this situation back in 1986 when the supply of vaccines were very much in doubt. Back then, vaccine manufacturers were facing a large number of law suits (although very few of them successful) and were threatening to pull out of the market entirely. Fast forward to today and the vaccine market is considered a growth market, with billions in dollars of revenue (e.g. Merck alone booked almost 1.4 billion dollars in revenue from the sale of vaccines in 2009).

When you file a claim with the so-called vaccine court, your claim is handled in several different ways, depending on the exact nature of the injury. If the injury is a commonly accepted one (i.e table injury) then your claim will be awarded quickly. If it is not, your case is heard by a special master and you have to prove that the vaccine caused the injury.

After following the the doings of the vaccine court for several years, I think I can safely say that the program is not living up to what it was supposed to be. Rather than the program being a swift alternative to the traditional courts, claims filed with this program can take many years to resolve - even for simple claims. And, as anyone who followed the autism omnibus proceedings can tell you, the process in the court is anything but "less adversarial".

This so-called court also seems to have a major aversion to using the word "autism" and vaccine together.  If you claim that your child has a vaccine injury as well as autism, the chance of you winning your claim is almost non-existent.

Even worse, in the few cases were the court has awarded damages when autism is involved, they have gone well out of their way to avoid making it seems like there could be any possible relation. For example, in the Hannah Polling case, the documents make reference to "features of autism" rather than autism directly. And even more telling, in the case of Bailey Banks, the special master actually created a new condition - "non-autistic" PDD-NOS.

 For anyone who has half a brain and understands the terminology involved, that phrase is like saying "non-wet" water or a non-automobile car.  PDD-NOS is, by definition, a form of autism and you cannot simply say that it isn't autism because we happen to know what caused it.

Just as a side note, while I don't think that vaccines leading to autism is all that common, if you don't think it is possible at all, go look at the Hannah Poling case.  Done?  Ok, save the "yes, buts" and just accept the fact that it can happen.  Even if we are only talking about this happening to 0.1 % of all children with autism, that would still be 40 children per year in this country alone.

The vaccine compensation program is operating without much oversight from the traditional court system and is basically being run by the same governmental organizations that are responsible for promoting vaccine use.  This arrangement gives the phrase "conflict of interest" a whole new meaning.  And, if you thing that the Special Master made any factual errors in the case or didn't consider the evidence properly, you are pretty much out of luck. As the US Court of Appeals for the Federal Circuit said in their recent ruling in the Cedillo case (starting on page 10)-
We review the Special Master’s factual findings using an “arbitrary or capricious” standard. We “do not sit to reweigh the evidence. [If] the Special Master’s conclusion [is] based on evidence in the record that [is] not wholly implausible, we are compelled to uphold that finding as not being arbitrary or capricious.” Our role is not to “second guess the Special Master[’]s fact-intensive conclusions” particularly in cases “in which the medical evidence of causation is in dispute.”
It will be interesting to see where this case goes. I suspect that the Supreme Court is going to uphold how the law is currently being interpreted, which means that it would be up to Congress to make any needed changes in how the program operates.

Time will tell.

Monday, October 4, 2010

Media Bias and The Pertussis "Epidemic"

I am constantly amazed at the inaccurate reporting that appears in major media sources, especially ones that are science oriented. In some cases it seems like there is a message that they want to get out and the facts are either ignored or forced into fitting the message.

Take for example the rhetoric about the pertussis (whooping cough) outbreak this year in parts of the country. If you were to follow what major media outlets are saying, you would believe that this is the worst outbreak in 50 years and that the reason for the outbreak is parents who are refusing vaccinations.

But, as I have talked about ad nauseum, the reality of the situation seems to be different.  It is true that parts of the country are experiencing outbreaks but, for the country as a whole, this is nowhere near the worst epidemic in 50 years. And more importantly, declining vaccination rates are only one possible explanation for the outbreak.

More likely reasons include the facts that pertussis outbreaks follow a cyclical pattern and happen every three to five years, that the number of pertussis cases have been on the rise since the 1980s, that the protection from the vaccine only lasts 10 years, or that there is evidence that the bacteria is changing the the vaccine simply isn't working as well. If you are interested in the details behind the facts, I would refer you to some of the earlier posts that I have written.

But none of these reasons seem to matter to the New Scientist in an article that they published a little over a week ago. The title of the article is "Whooping cough epidemic suggests bacteria are adapting" but the very first paragraph is as follows -
NINE babies have died in California, and four in Australia, so far, in the worst epidemic of whooping cough in rich countries since vaccination became widespread in the 1950s. The main cause is a lack of re-vaccination, but the bacterium may also be adapting to beat vaccines.
While the rest of the short article plays lip service to the idea that the there could be something else going on, the main theme is that the failure of people to use vaccines aggressively are behind the epidemic. Take for example the following statement -
Vaccination protects babies - these recent deaths have been in babies not yet vaccinated - but immunity wanes with age, so older children and adults can be unwittingly infected with whooping cough and infect unvaccinated babies.
While that statement is factually accurate, it leaves out one very important detail. The children who died didn't receive the vaccine because they were too young - not because their parents refused them. But this sort of nuance is completely absent from the reporting and has been replaced with an overriding "take your vaccines" message.

As for the assertion that this is "the worst epidemic of whooping cough in rich countries since vaccination became widespread in the 1950s", well I leave you with a pretty picture to dispell that notion.

The numbers on this chart are from the data published by the CDC and represent total number of cases week by week for the years 2004, 2005, 2009 and 2010. As you can see two years in very recent history have had far more cases at this point in the year.

Sunday, October 3, 2010

ADHD Is Now "Genetic"

According to a new study just published a few days ago in The Lancet, Attention-Deficit Hyperactivity Disorder (ADHD) might be a genetic disorder rather than just a social one.  I have not read the entire study yet, but I think what it is saying is rather straightforward.

The researchers looked at 366 children with ADHD and 1,156 unrelated adults and found that the children with ADHD were far more likely to have large, rare Copy number variants (CNVs) than the adult control group.  About 15% of the children with ADHD had one of these CNVs while only about 7% of the control group.  Based on this finding, the the researchers are suggesting that ADHD is a "genetic disease and that the brains of children with this condition develop differently to those of other children"

Although it is not completely clear in the abstract, I think that the CNVs found were mostly unique in each child, although there might have been several children in the ADHD that had a duplication on 16p13.11.  And yet, these mostly unique mutations are thought to help cause ADHD.

The similarities between this finding and what has been found in children with autism are striking.

These large, rare CNVs have been found to be more common in children with autism than the typical population.  But more than that, children with autism also show many different CNVs with very little overlap.  It is like each child has an almost unique mutation but yet these mutations are taken to have caused or contributed to the underlying disorder.  And, at least in children with autism, most of the time these mutations are not inherited from the parents but rather are "de novo" (i.e random) mutations.

The similarities between ADHD and autism don't end there -
  • Both conditions have historically been blamed on bad parenting.
  • Both conditions are more common in boys than girls. 
  • Both conditions have become significantly more common over the past 30 years but the cause of the increase or whether there has been an actual increase is disputed.
  • Both conditions are more common in some areas than others.
  • Both conditions involve difficulties with social situations.
  • Both conditions involve difficulties in being able to focus or pay attention to the outside world.
Even more interesting, at least to me, is that modern medicine has had very little luck in figuring out what is behind either condition.  Although in the case of ADHD, there are more treatment options available and several drugs that can help overcome the symptoms of the disorder.

Anyone want to make a bet that ADHD and autism will be found to have similar causes?


Rare chromosomal deletions and duplications in attention-deficit hyperactivity disorder: a genome-wide analysis
Dr Nigel M Williams PhD,Irina Zaharieva BSc,Andrew Martin BSc,Kate Langley PhD,Kiran Mantripragada PhD,Ragnheidur Fossdal PhD,Hreinn Stefansson PhD,Kari Stefansson MD,Pall Magnusson MD,Olafur O Gudmundsson MD,Omar Gustafsson PhD,Prof Peter Holmans PhD,Prof Michael J Owen MD,Prof Michael O'Donovan MD,Prof Anita Thapar MD
The Lancet - 30 September 2010
DOI: 10.1016/S0140-6736(10)61109-9