Friday, April 18, 2008

A micro history of the recent mercury autism controversy.

A commentary on: Aschner, M. (2008). Response to Article by DeSoto and Hitlan on the Rlationship Between Mercury Exposure and Autism. Journal of Child Neurology, 23(4), 463-463. DOI: 10.1177/0883073808314647

DeSoto, M.C., Hitlan, R.T. (2008). Concerning Blood Mercury Levels and Autism: A Need to Clarify. Journal of Child Neurology, 23(4), 463-465. DOI: 10.1177/0883073808314718

The latest issue of the Journal of Child Neurology includes two letters regarding the mercury-autism controversy. For most people familiar with this issue, this summary will not present anything new, but for those interested in knowing the basics of this latest controversy, here is a micro-crash course on the mercury-autism link.

In 2004 authors Ip, Wong, HO, Lee, and Wong, published an article in the Journal of Child Neurology comparing the blood and hair mercury levels of children with and without autism in order to examine if a mercury-autism link existed. The results were as follow:

There was no difference in the mean mercury levels [between the group]. The mean blood mercury levels of the autistic and control groups were 19.53 and 17.68 nmol/L, respectively (P = .15), and the mean hair mercury levels of the autistic and control groups were 2.26 and 2.07 ppm, respectively (P = .79).
The conclusion, which was supposedly inconsistent with the theory that mercury causes autism, shocked some members of the autism community. I said ‘supposedly’ because whether or not the mercury theory is correct, the manner in which the results are presented goes beyond what the data can actually say. Specifically, the authors concluded that:
Thus, the results from our cohort study with similar environmental mercury exposure indicate that there is no causal relationship between mercury as an environmental neurotoxin and autism.
The problem here is that this data only speak to concurrent levels of mercury and autism diagnosis. So it is entirely possible that in some children pre- or post-natal exposure to this toxin results in neurodevelopmental changes leading to autism symptoms. This idea does not imply that mercury levels would remain high in affected children. It only implies that that these children were exposed to this toxin. A similar example would be exposure to alcohol during pregnancy leading to fetal alcohol syndrome (FAS). Children with FAS do not have higher levels of alcohol in their blood than typically developing kids. I am not endorsing the mercury theory, but I am stating that the conclusions as stated by Ip go beyond what their data say.

But back to the Ip et al. (2004) study. In 2007, DeSoto and Hitlan published an article in the Journal of Child Neurology after they found a major mathematical mistake in the original findings reported by Ip. Specifically, they found that the non-significant differences in blood levels reported by Ip was an error and significant differences were actually observed. I did the calculations myself, and yes in fact, the kids with autism had significantly higher mercury levels than the control group (t = 2.6163; df = 135; p>.01).

Then in the latest issue of the Journal of Child Neurology, Dr. Michael Aschner published the following short correspondence:
In a recent article DeSoto and Hitlan1 reanalyzed an original data set, concluding that a relationship exists between blood mercury levels and the diagnosis of autism spectrum disorder (ASD). The conclusion is based on the reanalysis of hair to blood mercury ratios. Hair to mercury concentration ratios while informative need to be considered within the context of a temporal relationship. As elegantly demonstrated by Grandjean and colleagues, mercury levels in the hair reflect a delayed average compared to the blood mercury level averages. That is, mercury hair concentrations at hypothetical time point T reflect blood mercury levels at T minus 1 to 2 months. Chelation therapy and changes in diet and fish consumption (both more likely to occur in the ASD group) in the 2 months preceding the mercury analysis are likely to affect blood, but not hair mercury sample concentrations. The analysis by DeSoto and Hitlan, which presumes that the 2 biomarkers are equally affected, is clearly erroneous. Thus, absent appropriate corrections for the temporal fluctuations in mercury levels, the conclusions should be interpreted with utmost caution and revalidated taking the above issue into account.
This was followed by a response from DeSoto and Hitlan explaining further that their 2007 study addressed directly the error in blood sample Mean differences as reported by Ip et al in 2004. DeSoto and Hitlan re-analyzed Ip's data showing that in fact blood mercury levels in the autistic group were higher than in the control group. This finding, and the original Ip error, had nothing to do with hair-to-blood ratios as described by Dr. Aschner. Dr. Aschner criticism is much more applicable to a separate hair analysis performed by DeSoto and Hitlan showing that the autism group had lower hair mercury levels than expected based on their blood samples, which is inconsistent with the idea that chelation therapy may have affected the blood levels. I explain: blood levels reflect immediate levels of mercury while hair levels reflect levels 1 to 2 month prior to testing. Thus, if blood levels at Time 1 were 20 (I’m using random numbers as example), then hair levels at Time 2 (2 month later) should be 20. If after Time 1 the child undergoes chelation therapy, then theoretically, blood levels at time 2 (2 month later) should be lower than 20 but hair levels should remain 20. Thus at Time 2, blood levels should be lower than hair levels. This was not supported by DeSotos’ analyses. What does this mean? Simply that the differences in blood levels found between the autism and control group are unlikely to have been affected by chelation therapy in the autistic group since the hair-blood analysis was not consistent with what is expected if chelation therapy had occur. WARNING: this is not a statement supporting chelation therapy, it is just a clarification of a possible interpretation of this data.

Does this mean that vaccines cause autism? Not at all. Again, although we would like to think that data can give us the entire story, data speak in morphemes rather than words, or sentences. This data only indicate that this particular group of children with autism had higher mercury levels than typically developing children. This could mean many things, such as that the children with autism have difficulty processing mercury or that the children with autism were exposed to higher levels of mercury, and these explanations in turn, may or may not have anything to do with the symptoms observed in children with autism, both in terms of symptom presentation, severity, or causes. These data simply do not give us that information.

More recent articles about the Autism and Mercury controversy and the Autism and Vaccines controversy can be found here.

ResearchBlogging.org

Wednesday, April 16, 2008

Autism and social perception: The possible role of attention

Can the difficulties in social perception in Autism be due to attention deficits?

A review of: Fine, J.G., Semrud-Clikeman, M., Butcher, B., Walkowiak, J. (2008). Brief Report: Attention Effect on a Measure of Social Perception. Journal of Autism and Developmental Disorders DOI: 10.1007/s10803-008-0570-x

The co-morbidity between autism spectrum disorders and attention disorders (ADHD or ADD) is very high, with rates ranging from 49% to 78%. Thus, a significant number of people with autism spectrum disorders also have attention difficulties. Yet, little is known about how these attention problems may contribute to the different social difficulties experienced by people with ASD. In this paper, the authors compared 37 children with ASD (no breakdown of ASD was provided), 30 children with ADHD, and 19 typically developing kids (age 6-16). All kids had IQ scores over 80. 20 of the kids in the ASD group also had a co-morbid diagnosis of ADHD. These children completed a measure of social perception: the Child and Adolescent Social Perception Measure (CASP). This measure consists of 10 video clips of children interacting with an adult. The kids could see the vingnettes but the audio of the video was modified so that the kids could hear the prosody but not the lexical content. Then the kids were asked to tell the story in their own words and then indicate how each of the characters was feeling and how they could tell how the characters felt. Additional measures of attention and cognition were also included.

The results: ASD and ADHD kids did not differ in their ability to correctly identify emotions, but both groups performed significantly worse than the typically developing group. The ASD and ADHD groups also did not differ on measures of inattention or impulsivity, but the ADHD group had higher levels of hyperactivity. Finally inattention was a significant predictor of poor performance on the CASP. Thus, for all groups, lower levels of inattention were associated with better performance on the social perception measure, suggesting that for children with austim spectrum disoder, inattention may play a key role in explaining difficulties in non-verbal social understanding.

ResearchBlogging.org

Monday, April 14, 2008

Autism Treatments: Parent-Child Interaction Therapy.

Study provides evidence of the effectiveness of the Parent-Child Interaction Therapy for children with Autism.

A review of: Solomon, M., Ono, M., Timmer, S., Goodlin-Jones, B. (2008). The Effectiveness of Parent–Child Interaction Therapy for Families of Children on the Autism Spectrum. Journal of Autism and Developmental Disorders DOI: 10.1007/s10803-008-0567-5

The authors of this ‘in press’ manuscript reported the results of a study examining the effectiveness of Parent-Child Interaction Therapy for children with autism. This intervention was first proposed by Eyberg et al in 1995 and consists of a manualized parent coaching intervention for children age 2 to 7. This intervention was not initially developed for children with autism and instead was focused on helping parents with children with behavioral disorders. The intervention consists of live coaching sessions, during which parents interact with their children inside a room with a one way mirror. Behind the mirror a parenting coach provides live feedback via a microphone that is linked to earphones provided to the parents. The goal of the sessions is to help parents provide immediate reinforcement of positive behaviors while ignoring (extinguishing) dysfunctional behaviors. This study used a waiting-list control group design. That is, families were randomly assigned to one of two groups: a treatment group receiving the intervention, or a control (waiting-list) group which would receive the intervention later. The study included 19 children with an ASD diagnosis obtained via ADI-R. Ten children were assigned to the treatment group (6 AS,6 HFA)and nine were assigned to the waiting list group (2 AS, 4 HFA, 2 PDD). The treatment lasted 12 sessions. After the intervention the children in the treatment group showed a statistically significant reduction of problem behaviors as reported by parents when compared to the control group. There was also a statistically significantly reduction of ‘atypicality’ and an increase in adaptability. Marginal significant differences were also observed in hyperactivity. Although these results are all based on parental reports, which is a methodological problem, the authors also found differences in affect display as coded from video tapes of the sessions. Specifically, the authors found an increase in positive affect by the parents and an increase in how many times child positive affect followed the parents’ positive affect. In sum, this study provides early but compelling evidence of the effectiveness of Parent-Child Interaction Therapy for children with Autism who experience behavioral problems.


ResearchBlogging.org