Friday, January 30, 2009

So what's the harm?

There are reasons that there is so much nonsense out there concerning autism and reasons why parents tend not to trust their pediatricians when it comes to autism. Take the study that I just finished writing about, if you read the abstract for the study is it pretty clear what the study was about, but I would like to highlight one section from the abstract :

METHODS. Children who were enrolled in an efficacy trial of pertussis vaccines in 1992–1993 were contacted in 2003. Two groups of children were identified, according to thimerosal content in vaccines assigned randomly in the first year of life (cumulative ethylmercury intake of 62.5 or 137.5 µg)

From reading that excerpt you should understand that there were two groups that differed in their level of exposure to thimerosal.

Now, keep that in mind while I digress for a moment. Apparently Dr. Lewis R. First, the new editor of Pediatrics, is writing a blog to summarize the current issue of the journal. This is a good thing since increasing distribution of scientific research makes us all more educated.

If we look at his summary of the February issue you will see what he wrote about the above article :

Finally, we get to the heart of the immunization controversy with a study by Tozzi et al. on whether or not thimerosal can influence neuropsychological performance ten years after immunization in infancy (475-482). You’ll be reassured that the results show essentially no differences between groups who did or did not get thimerosal in their vaccines—and you’ll want to know this information when talking with parents of your patients about the safety and benefits of vaccines.

This passage makes me wonder if he actually read the article in question. If you look at the abstract it is very clear what the groups are, so what gives?

I first saw the discrepancy noted in an entry on the Age of Autism blog by David Kirby. Go read the full post, it is interesting exchange. The day after the post on Age of Autism, Dr. First posted a correction to his blog clarifying his position, for which I have to commend him. From the series on e-mail of Age of Autism it did not initially look like he was going to.

The question is what to make of all of this. I would have thought that the editor of Pediatrics would have been more familiar with the contents of an article, especially if he was writing a summary of it. So what I am left with is either that it was an honest mistake or, more likely, he took the someone else's spin on the study and ran with it.

Now, you may ask why any of this matters.

Consider if you are the normal pediatrician who is very busy doing their job. If you did not have a particular interest in this topic you would pick up the news reports that yet another study shows no link between thimerosal and autism. You might pick up the short summary from the editor of the journal who you would assume would know of what they are writing. Chances are you would not read the study itself let alone the abstract. So you would be left with the impression that this study showed something that it did not.

If you are a normal parent the situation is worse. At best you will see the headline and maybe, if you really care about the issue, you may read some other blog posts giving the white washed version of the study. You will never read the abstract of the study let alone the study itself.

So, does this really matter in the end? Does this sort of misinformation do any harm? I think it does.

Tuesday, January 27, 2009

Shooting fish in a barrel or another new thimerosal study

People wonder why some stories just won't go away. Take for instance the theory that the thimerosal (mercury) in vaccines is related to autism. This seems like a simple enough question to answer via science. After all, this is the sort of thing that science is supposed to be good at.

But, to date there has been no conclusive study that disproves the relationship between mercury and autism. There have been a decent number of half baked ones that make a token attempt to answer the question. These are the ones that are normally referenced by people like Dr Paul Offit to prove their point.

So, with that in mind, there is yet another study that was published in Pediatrics recently entitled Neuropsychological Performance 10 Years After Immunization in Infancy With Thimerosal-Containing Vaccines.

This was a follow up study done for 1,403 children in Italy who participated in an earlier study of the efficacy trial of pertussis vaccines. The study looked at the two different groups of children who received different amounts mercury from the vaccines and looked to see if there was any difference in outcomes. They basically found that there was no real difference between the groups.

Now, where to start with what is wrong with the study.

First, the two groups are based on different amounts of mercury exposure. Most of the time when you are looking for side effects you would want to compare how a group that was exposured to the substance did compared to a group that wasn't exposed.

Second, the study group contained only one child with autism - so out of 1,403 there was only one child. Since the current estimation of autism is 1 in about 150 I would have thought that there would have been more children with autism found.

Third, this study is just looking at exposure to one vaccine. It does not appear that they attempted to control for other sources of mercury that the children were exposed to.

Last, this study was funded in part by the CDC but done on a group in Italy. Now I have nothing against Italy but why can't the CDC fund a study that looks at the thimerosal/autism issue in the US for US based children?

I will be happy when the research is finally properly done to put this issue to bed once and for all so everyone can stop arguing about it and move on to something else. But for now it is yet another study that doesn't show what it is says it does.

From the "you are what you eat" category

There aren't too many people who are singing the praises of high fructose corn syrup these days. However, it seems like there might be another reason to avoid the stuff. According to a small pilot study published in Environmental Health journal some varieties might contain contain elemental mercury. The mercury is introduced into the product in one of the stages of manufacturing.

The punch line of the study is that since the average person consumes so much of this stuff on a daily basis there could be a problem with the amount of mercury ingested from this source. This would especially be a problem for children who would have more of a problem with it.

The study is located here. The study is open access which means that the full text is available to the public so if you are interested I suggest taking the time to read it. The Chicago Tribune also has an article about it here.

Wednesday, January 21, 2009

The press's autism boilerplate

The New York Times earlier this week published an article entitled Trying Anything and Everything for Autism. You would think that with a title like that it would be a hopeful story about parents trying to help their children on the spectrum in search of a cure.

You would be wrong.

Rather this article is one of the many boiler plate articles as of late that are attempting to sway public opinion about what autism is and how best to treat it.

It starts out like normal articles of this type talking about "the diagnosis" followed by some descriptions of treatments with a small nod to the fact that autism is not a uniform disorder :

It is also true that autism is highly variable, with periodic improvements and regressions, and most children receive several therapies at once. So it is difficult to say what makes things better or worse at a given time

which is unfortunately one of the last balanced statements in the article. From there we go straight to the FUD

We don’t know what would have happened if we had done nothing.

with a quick stop to listen to the voice of god (although in this case god has a son with autism) proclaim:

In “Defeating Autism: A Damaging Delusion” (Routledge, 2009), Dr. Michael Fitzpatrick, a general practitioner in London whose son is autistic, likened the alternative medicine approach to a return to “medicine’s dark ages.”

Every biomedical intervention, he wrote, “is supported by anecdotes and personal testimonies: it is understandable that parents want to share their experience that their child has made progress, and it is equally understandable that other parents are impressed by success stories.”

Dr. Fitzpatrick continued, “When parents have invested money, time, energy and, above all, hope into a particular treatment, it is natural to seek to attribute any improvement to that treatment.” But, he added, anecdotal examples and wishful thinking are not science.

and finishes up the the enlightenment of the one true treatment of ABA :

The one approach that has been scientifically validated to help, though by no means cure, autistic children is behavioral intervention that mimics the way normal children learn, Dr. Schreibman said.
the results are not instant, but it does work. But the earlier in a child’s life it is started, the more effective it is likely to be.

So, in a few short paragraphs we have the dark ages, wishful thinking on the parent's part, and, my favorite, anecdotal examples are not science. Followed by the one true path of ABA.

Don't get me wrong, I believe that ABA is an effective treatment to use, my own children are benefiting from it. I just don't believe it is enough on its own nor do I believe that it will work for every child.

This is the standard form for these articles now; the diagnosis, the brush with quackery, the voice of reason, followed by the use ABA and avoid the rest of that stuff.

Well, then, here is my question. Where is the science to prove or disprove how well these other treatments work? When a new drug is first introduced to treat some new disease or condition or restless legs it is normally described as "promising" and its potential to help people is played up. But when you are talking about treatments for autism they are "wasting valuable time, effort and money on remedies that lack a scientific basis and proof of effectiveness".

Autism has been around for many years in its current form and when you consider the original label was coined over fifty years you would have thought that there would have been enough time to evaluate some of these anecdotal examples.

Take for example the dietary changes that the article mentions, the gluten-free and casein-free (and sometime soy-free) diet that was mentioned. This is a very common intervention that is used by parents yet there are very few studies that have even looked at the question and none that have some so properly. Yet parent's keep doing it, so lets ask ourselves, why?

For myself I can answer that we pursue the diet for my twins who have autism because it worked - both twins showed a large improvement in eye contact and attention when their diet changed. Although in our case I believe it is mostly milk that they have an issue with.

So how about some science that identifies the subset of people with autism who many have issues with certain dietary elements which them proceeds to measure the physical signs of this intolerance. Then do a controlled study were you remove the substance in question and remeasure. This isn't rocket science.

There are plenty of studies looking for the genetic smoking gun that causes autism but so far none have been found. Why not take some of the funding for these genetic studies and investigate some of the other promising areas?

When you expect the very least

Let me just saw from the beginning here that I have historically found the autism blog at to be worth reading. However, as of late, Lisa Jo Rudy seems to going down, how shall we say it, a depressing path that seems to be leading up to giving up, or "acceptance" as some groups would call it. Consider this recent string of posts:

Do we expect too much from our autistic kids?
Amazingly, I saw no concern on the part of their parents that these kids were not making eye contact. No one seemed to care that they were not conversing. There was no expectation that they'd make their own beds or meals - or even speak on their own behalf to a clerk or waitress.

Yet children in autism support classes are expected, from a very young age, to make eye contact and learn to converse with their elders in a polite and civil manner. An autistic child caught playing on his own with a Gameboy is immediately pulled away from the activity and engaged in a social interaction. Children with autism are expected and taught to make eye contact, manage daily self-help activities, and generally participate in the adult world in a manner rarely dreamed of by typical children.


Bottom line - do we expect too much from our children with autism? My sense is - in many cases - the answer is a resounding "yes!"

So we are to believe that we are pushing our children too hard to learn the skills that they lack. That "normal" children don't do the behaviors that we push our children with autism to do.

The problem is here is that these skills that are mentioned such as eye contact, self help skills and participating in an adult world - these are skills that "normal" children will pick up on their own with just a little coaching. Many children with autism simply won't learn these skills without help.

Is independent living over-rated?
I'm also finding myself increasing frustrated by the realization that the expectations placed on adults with autism (and, in fact, all adults) are, to a very large degree, the invention of the past 60 years of cultural evolution.

In short, when it comes to adults with autism (or to families in general, really) - is independent living over-rated?

This one leaves me flabbergasted. Being able to live on your own is the invention of the past 60 years and it is over-rated to hope that your children will be to take care of themselves? What happens when you are no longer around or are unable to take care of your children?

Is it really possible to teach "social skills?"
As parents of children with autism (or awkwardness, shyness, a preference for solitude, or a desire for uniqueness), how much can - or should - we press our children to learn skills that are, by their very nature, almost unteachable? If we press our children to participate in complex, subtle relationships when they're neither ready nor willing - are we doing them a favor?

Once we've taught the social life skills and the basic social graces of etiquette - have we done enough?

And we should only try to teach the basic social skills and not try for the harder skills? If your child were "normal" would you stop trying?

So, to summarize, we are expecting too much for our children for them to try and help them learn basic interpersonal skills, we shouldn't expect them to be able to live on their own, and if we somehow manage to teach them to the basics of social skills, you ask yourself "have we done enough".

I think the answer is very simple. Autism is very profound disorder which by its very nature puts your children at a huge disadvantage relative to other children. Your job as a parent to teach them and help them as much as possible so they can become the best person they can be regardless of the issues like autism that they have to deal with.

You teach them so that when they are in a restaurant and a waitress hands them a plate, they know to take the plate. Your "normal" child might not take the plate but at least they understand that is what is requested of them.

You teach them so that when they are older they will have a chance to be able to support themselves, live indepenantly, and take care of themselves. Most "normal" children will be able to do this.

You teach them so that they will have a chance to form meaningful relationships with other people and have a chance to get married and have a family of their own someday - assuming that is what they want to do. "Normal" kids do it all of the time.

You do not stop trying to help your children.

Friday, January 16, 2009

Study Watch : Immune to studies

A few studies came out at once. I have yet to read any of the actual studies but they look interesting:

Serum anti-nuclear antibodies as a marker of autoimmunity in egyptian autistic children.
Autism may involve an autoimmune pathogenesis in a subgroup of patients. The frequency of anti-nuclear antibodies in 80 autistic children and their relationship to a family history of autoimmunity were studied, compared with 80 healthy, matched children. Children with autism had a significantly higher percent seropositivity of anti-nuclear antibodies (20%) than healthy children (2.5%; P < 0.01). Fifty percent of anti-nuclear antibody-seropositive autistic children had an anti-nuclear antibody titer of >/=1:640 (very high positive); 25%, >/=1:160 (high positive); and the remaining 25%, 1:80. All anti-nuclear antibody-seropositive healthy children had anti-nuclear antibody titers of 1:80. A family history of autoimmunity was significantly higher in autistic children (47.5%) than healthy controls (8.8%; P < 0.001). Anti-nuclear antibody seropositivity was significantly higher in autistic children with a family history of autoimmunity than those without such history (36.8% and 5%, respectively; P < 0.001). Anti-nuclear antibody seropositivity had significant positive associations with disease severity, mental retardation and electroencephalogram abnormalities. Autoimmunity may play a role in a subgroup of children with autism. Further studies are warranted to assess anti-nuclear antibody seropositivity, other markers of autoimmunity (e.g., brain-specific autoantibodies), and the role of immunotherapy in children with autism.

Immune involvement in schizophrenia and autism: Etiology, pathology and animal models.
There is increasing evidence of immune involvement in both schizophrenia and autism. Of particular interest are striking abnormalities in the expression of immune-related molecules such as cytokines in the brain and cerebral spinal fluid (CSF). It is proposed that this represents a permanent state of brain immune dysregulation, which begins during early development. One possibility is that maternal infection, a known risk factor for schizophrenia and autism, sets this immune activation in motion. Several animal models are being used to investigate this hypothesis. There is also recent evidence that, among schizophrenic subjects, those associated with maternal infection display a distinctive pathology, which suggests that diverse causes for this disorder may explain some of its heterogeneity. The human and animal results related to immune involvement suggest novel therapeutic avenues based on immune interventions.
Increased IgG4 levels in children with autism disorder.
Accumulating evidence indicates that immune dysfunction is associated with autism disorders in a significant subset of children. Previous reports have shown abnormal immunoglobulin (Ig) levels, including an increased presence of autoreactive antibodies in the circulation of individuals with autism. As IgG is the predominant antibody isotype in circulation, we expected that an altered immune response could result in an abnormal IgG subclass profile in children with autism. We examined circulating plasma levels of IgG1, IgG2, IgG3, and IgG4 in 241 children from the CHARGE (Childhood Autism Risks from Genetics and the Environment) study, a large epidemiologic case-control investigation, including 114 children who meet full criteria for autism disorder (AU), 96 typically developing control children (TD) from a randomly selected sample of the general population, and 31 children with developmental delays (DD). We report significantly increased levels of the IgG4 subclass in children with AU compared with TD control children (p=0.016) and compared with DD controls (p=0.041). These results may suggest an underlying immunological abnormality in AU subjects resulting in elevated IgG4 production. Further investigation is necessary to elucidate the relationship between immunological findings and behavioral impairments in autism.

Study Watch : Systematic review of early intensive behavioral interventions for children with autism.

Systematic review of early intensive behavioral interventions for children with autism.
Recent reviews highlight limitations in the evidence base for early interventions for children with autism. We conducted a systematic review of controlled studies of early intensive behavioral interventions (EIBI) for young children with autism. Eleven studies met inclusion criteria (including two randomized controlled trials). At group level, EIBI resulted in improved outcomes (primarily measured by IQ) compared to comparison groups. At an individual level, however, there was considerable variability in outcome, with some evidence that initial IQ (but not age) was related to progress. This review provides evidence for the effectiveness of EIBI for some, but not all, preschool children with autism.
Or to paraphrase, we reviewed other studies and it looks like it works on the whole but we don't know why it works or doesn't work on an individual level. I need to read this one.

For homework, read the study

I have been reading the autism blog at for a while now. It started out as a decent enough site with a fairly balanced take on the issues and concerns of the autism world. As of late it has taken a turn for the worse.

Take this sequence of posts on a new study that was conducted by the MIND institute in California.

Rise in autism prevalence in CA likely due to environmental issues, suggests UC Davis study

The first post was published on a Friday when the initial press releases came out. Lisa Jo Rudy, the blog author, starts out by expressing her doubts about the study and quotes the press release. OK, fair enough.

Questioning the new MIND study on prevalence of autism

The second post is published the next day on Saturday. Lisa is noting an article in Scientific American about the new study. She includes some of the text from the article and expresses her doubts about it again.

What does the MIND study on autism prevelance really say?

The third post is published on the Sunday. In this post Lisa is comparing the press release and the abstract for the study and, surprise, expressing her doubts about the study again. She goes on to compare and contrast the abstract of the study with the press release for the study and points out the inconsistencies between the two.

Here is a thought. If you are going to be reviewing a study and are going to be writing multiple blog posts on the subject, wouldn't it be worth the time and effort to actually read the study that you are writing about?

When you consider the title of the third post we are getting into ironic territory.

Notes from MIND researcher Dr. Irva Hertz-Picciotto

For the final post on this topic which comes on Tuesday, five days after she has started writing about the study. To give Lisa credit she has finally done some more research on the study and talked to one of the authors of the study about what it says instead of reading press releases, news stories, and abstracts.

However, it does not appear that she has actually read the study yet.

I would suggest that if you are going to take the time to write so much about a study that you take the time to read it first.

For those interested, the study is available to non-subscribers for a cost of $35 from the publisher's site.

Correlation, Causation, and non-sense

I have seen this argument a lot as of late. It normally runs the standard course of correlation does not imply causation with a good implication of just because there is a correlation does not imply a relationship.

Unfortunately it isn't really true.

It is true that a correlation between two variables, say for example the weather and autism rates, does not imply that one causes the other. But it does not rule it out either.

So making a statement about implying a lack of causation is as wrong as saying that there is causal relationship - there simply is not enough data from a correlation to say either way. Actually, for causation there first has to be a correlation, but I digress. In reality the best you can do is make a neutral statement.

However, a correlation does say that these two variables have a relationship where they change in tandem, ie they are not independent. This means that the variable are related in some way or there is some other factor to which they both respond.

So at that point you either a) have bad data b) have a spurious correlation or c) there is a relationship between the variables.

For a better explanation of this I suggest reading the below

So going back to the ice cream and murder from the post that I linked to, the correlation between the two apparently unrelated items does show that they both can sometimes be related to some outside factor, in this case the weather can effect both. So while ice cream sales and murder don't cause one another they do have a causal factor in common, the weather. Not that this implies that the weather is the only factor driving both, it simply implies that it is a factor.

Or, while we are talking about the weather, if you have studies showing a correlation between autism rates and the weather while it does not follow that the weather causes autism or cause autism to be diagnosed, it does follow that there is some common factor between the two (assuming that there is not some problem with the data or the study). Which implies that there is something related to the environment that can effect autism. And for a disorder that is taken to be strictly genetic that would be a bit of pickle.

But I guess that is the real issue anyway. As a parent, if I see a therapy change the behavior of my child with autism, authors like the above would have me doubt that the therapy worked. Or if I change my child's diet and see drastic improvements in attention and eye contact, that might have just happened anyway with out the diet change.

After all, just because B follows A doesn't mean that there is a relationship. Taken to the extreme, just because I turn the door handle on a door and the door opens, it does not follow that me turning the handle opened the door, right?

Only it turns out that once you start down that road you can't really prove a relationship between any two events at all. I push the key on the keyboard and a letter appears on the screen of the computer - what evidence do I have that the two have any real correlation let alone a causal one?

It is a good thing that people have the ability to reason. After all, you might have identical twin girls who both get a shot on the same day, both develop a fever within the next 24 hours and spend the next month sick and mostly non-responsive. And after the end of the month you give them another shot because everyone knows they are perfectly safe and the doctor is saying that you should do it. And then you spend the next six months wondering if they can still hear when they answered to their names before but now don't respond to any sounds. Then the diagnosis.

Could it have happened anyway? Of course. Was there any relationship between the shots and the regression? There is no way to know for certain. Would it have happened regardless of the shots? Again, that isn't knowable. But, given the fact that they are genetically identical yet separate people and they both had the same reaction and the same time (illness) it makes it less like likely to be just chance and more likely to be a potential factor in the equation, just like the hot weather helps to sell ice cream.

But I am guessing this will be just another one of those meaningless correlations for some people. Just because it happened to one, oops, I mean two, people the same way at the same time means nothing.