Another study, published recently in PLoS One, fails to show a correlation between mercury and autism. This was a study of mercury excretion in the urine, comparing subjects with autism to their siblings as well as controls without autism spectrum disorder (ASD), both in mainstream and special schools. They found no significant difference among the groups, even controlling for kidney function (creatinine clearance), age, gender, and amalgam fillings.

To put this study into context – there are those who claim that mercury toxicity is what causes ASD, and in fact ASD is simply misdiagnosed mercury toxicity. There is no question that mercury is indeed a neurotoxin, but toxicity is all about dose, so the question is are children being exposed to mercury in high enough dose to cause toxicity. Further, it is difficult to extrapolate from preclinical studies (in test tubes and petri dishes) to living organisms. We need to further know what happens to the toxin in the body, and how the body handles it.

With regard to the forms of mercury found in some vaccines (although much less than in previous years) and tuna fish, the body seems to rid itself of the mercury sufficiently quickly to prevent build up to toxic levels. Of course, this remains a hot topic because of the persistent claims by the anti-vaccine movement that vaccine cause ASD, and some who cling to the discredited notion that it is mercury in vaccines that is the culprit. There are also the so-called “mercury militia” who blame environmental mercury (from vaccine and elsewhere) on all human illness, not just autism.

As further background, it’s helpful to note the chain of argument that has occurred with respect to the role of mercury in autism. Studies have consistently found no correlation between mercury exposure and the risk of ASD. Proponents of the mercury hypothesis have therefore argued that there is a subpopulation of vulnerable children who metabolize and excrete mercury differently than the general population, and it is within this subpopulation that mercury causes ASD.

Logically this may be true, but the argument is little more than special pleading, although a common one. Scientists are familiar with the usual list of special pleading arguments made to dismiss negative evidence. These include: that the dose studied was too low, the treatment duration was too short, the placebo or comparison treatment was also effective, or the looked-for effect only exists in a subpopulation. Each one of these arguments is logically consistent – if true they would explain the negative results without meaning that the phenomenon is not true. They may even be true in specific cases. What makes them special pleading is when they are invoked ad hoc to explain negative evidence without good justification.

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Autism is a spectrum of neurological disorders that involve, primarily, reduced social aptitude. People with autism tend to make less eye contact, they have less of a response to viewing a human face, and they are less verbal. Half a century ago autism was blamed on bad parenting, but that view is now considered outdated and even cruel. Autism is a brain disorder. Neuroscientists are learning more and more about what is different about autistic brains from more typical brains. One feature seems to be reduced communication among neurons in the brain.

Autism is diagnosed clinically. It is usually first recognized by the parents, who then bring their child to medical attention and after an evaluation the diagnosis is made. At present there are no supporting laboratory tests – we don’t diagnose autism by an MRI scan, EEG, or blood test. It is diagnosed by clinical observation and some standardized questionnaires and cognitive tests. At the more subtle end of the spectrum the diagnosis may not be made right away, not until the child is a bit older and can be more thoroughly evaluated.

The median age at diagnosis was 4.4 years in 1992. This has steadily decreased, to less than 3.4 years by 2001. This effect is greater in higher socioeconomic status (SES) groups. Low SES children are diagnosed later than higher SES children, and this gap has widened in the last 20 years.

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The recent issue of Neuron has a series of articles providing more information about the genetics of autism spectrum disorder (ASD). ASD is characterized by decreased social ability as a core feature, with other clinical features being variable. It is also not a single disease or disorder, and not just because of the spectrum of clinical features. Like many clinical entities, there can be many underlying causes that result is similar-looking clinical effects.

While debate rages as to possible environmental triggers or even causes of ASD, researchers have been slowly building a picture of ASD as a complex genetic syndrome. Literally hundreds of genes have been potentially implicated. Many of the genes linked to ASD are involved with brain proteins or brain organization.

The recent studies in Neuron look specifically at families with a single child with ASD. In families with multiple children, or with a parent and child on the spectrum, the disorder is likely inherited. But what of families with only one child with ASD, and at least one child without, with no affected parent? Such a pattern can also be consistent with an inherited disorder, if it is recessive or X-linked. In a recessive disorder both parents can be unaffected carriers, and 25% of children will be affected – so having a single affected child is not unusual. However, ASD genes tend to be dominant, which means at least one parent should be affected along with at least 50% of children.

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Over the last 20 years the prevalence of autism (now part of autism spectrum disorder, ASD) has been increasing. The medical community is largely agreed that this increase is mostly due to expanding the diagnostic category and greater efforts at surveillance. There remains some controversy over whether or not these factors explain all of the measured increase, or if there is a small real increase hidden in there as well. But largely – we are finding more children with ASD because we are casting a wider net with smaller holes.

If this is true, then we do not yet know what the true prevalence of ASD is. There must be a pool of undiagnosed children out there. Eventually the measured prevalence will hit the ceiling of the true prevalence (unless, of course, we expand the definition further) – but where is the ceiling?

That is the question researchers recently set out to answer, and they did so with a comprehensive 5 year study conducted in South Korea. The results surprised even them:
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I have been following the literature on autism diagnosis both because of my general interest as a neurologist, but also because it is at the center of the vaccine-autism myth. There is no question that autism diagnoses have been on the increase over the last 20 years. There are some who assume that this increase in the number of diagnoses being made represents a true increase in the incidence of the disorder – hence an autism “epidemic”.

However, careful analysis reveals that the increase in diagnosis is largely explained (perhaps completely explained – but a small real increase cannot be ruled out) by increased awareness of autism and an expanded diagnosis. (See my earlier posts for a full explanation.)

A recent study sheds further light on this issue. The study was not addressing the broader question of the causes of the increase in autism diagnosis, but rather was focusing on socioeconomic disparities in diagnosis. The results, however, do lend support to the conclusion that the rising autism diagnoses was largely due to increased awareness, rather than a true increase.

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We can add one more study to the pile of evidence showing no association between exposure to thimerosal (a mercury-based vaccine preservative) and autism. The article: Prenatal and Infant Exposure to Thimerosal From Vaccines and Immunoglobulins and Risk of Autism, is published in the latest issue of Pediatrics, and shows no association between prenatal and infant exposure to thimerosal and three forms of autism – autism, autism spectrum disorder, and regressive autism.

No one study can ever be definitive, but now we have a large body of evidence from multiple studies showing a lack of association between thimerosal and autism. This won’t stop the dedicated anti-vaccinationists and mercury militia from continuing their anti-vaccine propaganda, but hopefully it will further reassure those who actually care about the science.

Background

This has been a long and complex story, so let me review some of the background. Diagnosis rates of ASD have been climbing for the last 20 years, prompting some to search for an environmental cause. The existing anti-vaccine community, not surprisingly, blamed vaccines. This was given a tremendous boost by the now-discredited study by Andrew Wakefield concerning MMR (which never contained thimerosal) and autism. When the evidence was going against MMR as a cause, attention turned to thimerosal in some vaccines. This notion was popularized by journalist David Kirby in his book, Evidence of Harm.

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This is a quick update on the Autism Omnibus hearings – representative cases heard before a special court to decide if there is any credible evidence to conclude that autism may be a vaccine injury. After hearing exhaustive testimony by all sides, the special masters determined that the evidence does not support a link between autism and vaccines.

One of the cases heard was the Cedillo case, which was used as the test case for the theory that the MMR vaccine plus exposure to thimerosal can trigger brain damage that looks clinically like autism. In February of 2009 the court rejected the claim that Michelle Cedillo’s autism was caused by vaccines. No only was the theory of causation without scientific backing, evidence was presented to show that Michelle Cedillo demonstrated early symptoms of autism prior to ever receiving the MMR vaccine.

In fact the Cedillo case is representative of a fact that scientific research is increasingly demonstrating – that subtle signs of autism are present prior to parents noticing that there is a problem and long before formal diagnosis. The consensus of evidence is that signs of autism appear between 6-12 months of age, and maybe earlier in some cases. Meanwhile, the first MMR vaccine is given at 12 months. Since causes must precede effects, this fact alone is fatal to the MMR-autism hypothesis.

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In order to teach science to the public it is better to tell a story about how questions are resolved in science, rather than simply to teach authoritatively the current findings of science. The process is interesting – often more so than the facts.

One such story is the true cause of the increasing autism prevalence over the last 20 years. There is no question that the number of people being diagnosed with autism is increasing. There are various theories as to why, the best, in my opinion, is that the increasing numbers are an artifact of broadening the diagnosis and increased surveillance. Meanwhile, a true increase may also be hiding in the numbers, and that would present an interesting (and important) mystery to solve.

I have written about this before (here and here on SBM, and again here on NeuroLogica). Now there is a new study which may shed some light on the question, but to quickly summarize where the evidence is: There are several ways to address the question of whether or not there is a true increase in autism numbers. One is to assess autism prevalence at various age groups. If true autism incidence is increasing, that younger age groups should have more diagnoses of autism than older age groups – when the same diagnostic criteria are applied. When this kind of analysis is done it appears that autism incidence is stable over time, which is powerful evidence against a true increase.

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It has been a slow blogging week for me. I have been far busier than I thought completing my project – which I will be happy to tell you all about once I have the green light to promote it.

Meanwhile, here is an excellent article by Trine Tsouderos regarding OSR#1, which is an oral chelator being used by some to treat their kids with autism. The marketing of OSR#1 represents many of the problems that I and others have been blogging about for years.

OSR#1 was originally developed as a chelating agent to be used in industry – not for medical use. It binds to heavy metals, like mercury, and therefore those in the anti-vaccine community who still cling to the discredited notion that autism is a form of mercury toxicity believe it can be used to treat autism.

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I am out of town this week on a special project – more details will follow when I have the green light to start promoting it. So my posting will be a bit erratic this week.

Just a quick post for today. I want to point out that Age of Autism, the anti-vaccine propaganda blog of Generation Rescue, has really gone over the top in their witch hunt against anyone who dares try to educate the public about vaccines and correct the constant flow of misinformation that comes from the anti-vaccine ideologues. Their chosen method of attack is alleged conflicts of interest – and it is truly a witch hunt.

The core features of a witch hunt are that the accusation of guilt is treated as being equal to guilt, and that the rules of evidence of so fluid and vague that even “spectral” evidence is accepted – anything that creates even the impression of guilt.

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