Mercury Exposure and Autism: Should you check for nearby power plants?

...But this study is compelling in showing an association between mercury exposure and autism rates, and scientists can not just ignore it under the basis of its imperfect design and inability to make causal links – if that is the case, then only carefully controlled laboratory studies, with poor external validity, should be published and accepted as contributors to our greater scientific knowledge.

A review of: PALMER, R., BLANCHARD, S., WOOD, R. (2008). Proximity to point sources of environmental mercury release as a predictor of autism prevalence. Health & Place DOI: 10.1016/j.healthplace.2008.02.001

This fascinating, yet bound to be controversial, study hit the news yesterday as it was made available (pre-publication) by the Journal Health & Place. The study is simple, straightforward, elegant, with some powerful findings. In fact, the findings are somewhat daunting given the simplicity of the design. The researchers reviewed the amount of mercury release reported by industrial facilities and power plants in the State of Texas in 1997 from data provided by US Environmental Protection Agency Toxics Release Inventory. They compared these data against autism rates in 1997 and 2002 as measured by schools' autism classifications provided by the Texas Education Agency. Using a specialized geographical analysis system, the authors were able to locate each source of mercury and calculate the distance between each mercury source and each school. The results:

Industrial release of mercury and distance to industrial sources independently predicted increased rates of autism. The association with industrial release of mercury was not linear, instead the statistical model fit suggested an accelerated risk. This association remained statistically significant after controlling for specific variables such as SES, urbanicity, and race.

Power plant release of mercury and distance to power plant independently predicted increased rates of autism. In this case the association was linear (not accelerated). Again, this association remained statistically significant after controlling for other variables.

It is easy to dismiss these findings as inconsequential because they are ‘correlational’ in nature, or do not really prove anything. Researchers are too often guilty of selective acceptance of research: those studies that fit the consensus are accepted while those that don’t are dismissed for their methodological flaws – even though the studies we accept are equally flawed.

In the spirit of fairness I have to say that these findings are strong. Their methodology and analytical process are not any different from what is commonly seen in social science or epidemiology research. Is it perfect? Far from it. Is it useful or informative? Definitively! The data speak very clearly: In Texas, mercury release from industrial sources and power plants in 1997, and school proximity to these sources, are associated with rates of autism in 2002 as measured by school special education classifications.

Does this mean that mercury causes autism? Not at all. In the last sentence of the previous paragraph you can not replace the words are associated with with the word cause. There is a major difference. The data, albeit strong, have limitations. For example, the most obvious (to me) alternative explanation is that mercury release and proximity to these sources is also associated with another mystery factor that is causing this apparent association and that in fact, mercury release has nothing to do with autism rates in 2002. Let’s hypothesize that these power plants and industrial sources also release another toxin – let’s call this toxin autisimic (this is a made up toxin). These sources release mercury and autisimic at the same rate, so for each pound of mercury released there is a pound of autisimic released. It is possible then that this autisimic toxin directly increases the risk for autism, and this could explain completely the strong (but now obviously inaccurate) association between mercury release and autism.

Does this study show that vaccines cause autism? Absolutely not. I know this question may sound ludicrous to some, but I pose it rhetorically because I am certain that some will make the wide leap and link these findings to the vaccine issue.

There are other problems and limitations with this study, such as how autism rates were calculated (using all children instead of only those born inor after 1997), whether the autism rates are truly climbing and not explained by other factors, whether there are other variables that could be explaining this relation, etc, etc --- and yes, this study does not prove or directly indicate that autism is caused by mercury exposure (click here for a much more critical review of this study). But this study is compelling in showing an association between mercury exposure and autism rates, and scientists can not just ignore it under the basis of its imperfect design and inability to make causal links – if that is the case, then only carefully controlled laboratory studies, with poor external validity, should be published and accepted as contributors to our greater scientific knowledge. This is study is far, far, from perfect, and many changes should have been requested prior to publication, but I can say the same of 90% of what is published today.

Autism and the gender gap

Typically developing boys score higher than girls on autism scale.

A review of: Williams, J.G., Allison, C., Scott, F.J., Bolton, P.F., Baron-Cohen, S., Matthews, F.E., Brayne, C. (2008). The Childhood Autism Spectrum Test (CAST): Sex Differences. Journal of Autism and Developmental Disorders DOI: 10.1007/s10803-008-0558-6

This large-scale study examined gender differences in the Childhood Spectrum Test, a parental report of autism symptoms for use in primary schools. The test consists of 37 questions covering communication, social behaviors, and other symptoms of Autism Spectrum Disorder, but more specifically Asperger’s syndrome. A score of 15 or above is considered to be in the clinical range suggesting the presence of an ASD. The test was completed by 3,334 parents of typically developing kids attending elementary schools in England. There were equal number of boys and girls. The results were compelling. Boys had a statistically higher median score than girls (5 vs. 4, p < .001). But most notable, 103 kids (3%) had scores in the borderline range (12-14). This group was composed of 75 boys (73%) and 28 girls (27%). In addition, 102 kids (3%) had scores in the clinical range (>14). As you may expect, 79% (81) of these were boys.

Is the gender gap observed in the parental responses to this particular scale a reflection of true gender differences in the rate of ASDs – as predicted by the Extreme Male theory of Autism? Or do these results tell us more about a possible fundamental bias in our view of expected behaviors as they relate to ASDs? That is, gender differences may exist in communication styles, play preferences, and social behaviors, which are often view as ‘soft’ signs of autism spectrum disorders. Unfortunately this particular study will not give us the answer, for the results are consistent with both theories. It is also possible that both positions are not unique, or orthogonal, since the gender differences in communication styles, etc, may result from the underlying mechanisms proposed by the Extreme Male theory: a male tendency for systematizing and an impairment in empathizing.

Autism and Cerebellar Differences?

Study finds no differences in cerebellar volume in people with autism after controlling for macrocephaly, IQ, and age.

A review of: CLEAVINGER, H.B., BIGLER, E.D., JOHNSON, J.L., LU, J., McMAHON, W., LAINHART, J.E. (2008). Quantitative magnetic resonance image analysis of the cerebellum in macrocephalic and normocephalic children and adults with autism. Journal of the International Neuropsychological Society, 14(03) DOI: 10.1017/S1355617708080594

As I do my weekly literature search on Autism Research for Translating Autism, I noticed a number of forthcoming manuscripts about the role of the cerebellum in Autism. I will likely review some of these new studies and decided to start with Cleavinger et al (2008) MRI examination of cerebellum in children and adults with autism.

The cerebellum is located on the lower back region of the brain and traditionally it has been implicated in the integration of sensory information and the coordination of movement. However, more recent investigations have determined that the cerebellum is also active in various higher-order functions such as language, emotion, and cognition. In the past, studies looking at differences in the cerebellum of people with and without autism have provide mixed results with some showing increased volume in people with autism, while others show no difference, or decreased volume. One possible explanation for these conflicting findings is that people with autism often vary in degree of macrocephaly (large head size) which may affect the results if the samples studied included individuals with and without macrocephaly. To address this question the authors of this study examined 4 groups: a) people with autism and macrocephaly (N=13) b) people without autism and macrocephaly (N=8) c) people with autism and without macrocephaly (N=28) and c) people without autism and without macrocephaly (N=16). In general, after controlling for macrocephaly, age, and IQ, no statistically significant differences in cerebellar volume were found, although a trend was observed in that people with autism who also had macrocephaly showed smaller cerebellar volume as compared to similar macrocephalic individuals without autism. This trend is important because the ‘non-significant’ differences reported here are likely due to the small sample size and unequal group size, which affects the statistical power of the analysis (making it more difficult to show statistical significant differences even when such differences actually exist). But even if the 'non-differences' result is replicated and in fact no differences in cerebellar volume exist between these groups, does this mean that the cerebellum is not implicated in autism? Not at all. Here again I touch the issue of how we should avoid reaching conclusions that go beyond what the data tell us. These results only speak to the size of the cerebellum, suggesting no apparent morphological differences. These results however, do not speak to possible anomalies in the functioning of the cerebellum, which may or may not be present in autism.