Journal of Toxicology. Volume 2009, Article ID 532640, 7 pages

Who were the authors of the study?

J. B. Adams, M. Baral, E. Geis, J.Mitchell, J. Ingram, A.Hensley, I. Zappia, S.Newmark, E. Gehn, R. A. Rubin, K.Mitchell, J. Bradstreet, and J.M. El-Dahr

What was the study about?

This study investigates the possible relationship of the severity of autism to the body burden of toxic metals and RBC glutathione levels. It examines the correlation between the severity of autism (assessed by the ATEC, PDD-BI, SAS, and ADOS) and the urinary excretion of toxic metals, (both before and after taking DMSA), and further with the initial glutathione (in the red blood cells). 

What previous research supports the hypotheses of the study?

Previous research found that the amount of airborne pollutants, and especially mercury, correlated with an increased risk for autism. Another study found that blood levels of mercury correlated with the diagnosis of autism. A small study found that children with autism had 2 times higher levels of mercury in their baby teeth than typical children. Finally, one study investigated an oral chelation medication approved by the FDA for treating infantile lead poisoning, and found that children with autism excreted 3.1 times as much mercury in their urine.

What were the methods used in the study?

The four tools used to assess the severity of autism were the PDD-BI, ATEC, SAS, and ADOS.

DMSA is a licensed medication for treating lead poisoning and indicated in cases meeting toxic criteria. It acts by forming sulfhydryl linkages to divalent metal cations, forming a chelated metal complex which is then excreted in the urine. It is widely used off-label for other metal exposures, for example, mercury. In this study, DMSA was administered orally in 9 doses of 10 mg/kg, 3 times daily, over 3 days. Urine was collected for approximately 8 hours prior to taking the DMSA, and for approximately 8 hours immediately after the 9th dose.

What were the findings of the study?

The correlation analysis found multiple positive correlations between the severity of autism and the urinary excretion of some toxic metals (both before and after taking DMSA). Lead (after DMSA) and antimony (at baseline) had the most consistent effect, but other metals were also important. The average of all of the 76 sample correlation coefficients was 0.14, with a P-value of less than 10−10, indicating a high overall positive correlation between the severity measures as a group and the biological measures taken as a group.

The multiple regression analysis found that variations in the severity of autism could be partially explained by the urinary excretion of toxic metals and initial glutathione, with adjusted R2 values ranging from 0.22 to 0.45, and P-values all below .005. Lead (after DMSA) and antimony (at baseline) had the most consistent effect, but other metals were also important.

How did authors ensure that their correlations represented actual relationships?

The authors used the Bonferroni approach to ensure that very few nonsignificant correlations were misrepresented as significant. They also used the False Discovery Rate (FDR) method to control the expected number of false positives among the cases declared significant. The Bonferroni approach and FDR were used to analyze the correlations between the severity of autism and the urinary excretion of toxic metals, as well as the initial glutathione levels. The regression analyses found that the variations in the severity of autism could be partially explained by the urinary excretion of toxic metals and initial glutathione, with adjusted R2 values ranging from 0.22 to 0.45, and P-values all below .005.

What conclusions were drawn from the findings of the study?

The findings suggest that there is a high overall positive correlation between the severity measures as a group and the biological measures taken as a group. There were multiple positive correlations between the severity of autism and the urinary excretion of some toxic metals (both before and after taking DMSA). Lead (after DMSA) and antimony (at baseline) had the most consistent effect, but other metals were also important. The Bonferroni approach and False Discovery Rate (FDR) analyses both suggest that there are significant correlations between the severity of autism and the urinary excretion of toxic metals.

What should future researchers study?

Future studies should research the relationship between the severity of autism and the urinary excretion of toxic metals, as well as the role of initial glutathione levels, to further explore the potential causal relationship between the two. Additionally, further research should be conducted to determine the best fit to the sample data for the selected model, taking into account the correlation among the independent variables.

What were the limitations of this study?

The ATEC assessment was competed 2-3 weeks before the children took the 3-day round of DMSA, while the PDD-BI, SAS, and ADOS assessments were done 2-4 weeks afterward. However, there was a strong correlation between the ATEC and PDD-BI.

More participants completed the ATEC assessment than the other assessments.

Can I read the full study somewhere?

Of course. Check it out here.