I'm not trained as a public health scientist, but I've learned how to decipher epidemiology studies since I started working at PAN — and a good thing, too, because this stuff is interesting.

Case in point: A new study reports that when developing mice are exposed to a pyrethroid insecticide called deltamethrin, it results in impacts on brain chemistry and changes in behavior similar to what's observed in attention deficit hyperactivity (ADHD). Like I said, interesting stuff.

We know that increasing amounts of pyrethroid pesticide metabolites have been found in children's urine, raising concerns over potential neurodevelopmental effects. These researchers also analyzed data from the National Health and Nutrition Examination Survey (NHANES), and found that children with elevated metabolites of pyrethroid pesticides in their urine were more likely to be diagnosed with ADHD.

Why does ADHD exist?

It's been difficult for ADHD researchers to establish a strong “single gene effect” for ADHD, suggesting a couple of potential alternatives: 1) ADHD is caused by multiple genes; or 2) environmental factors or gene-environment interactions may contribute to ADHD. “Candidate” genes that make “small but significant contributions” to likelihood of ADHD have been identified.

Associations between ADHD and maternal exposure to environmental contaminants during pregnancy have been identified in past epidemiologic studies. In past studies, increased risk for diagnosis with ADHD has been associated with a number of potential indicators: lead exposure, low birth weight, and maternal nicotine use are a few.

This wide range of exposures does, however, have a likely biological mechanism in common — the catecholaminergic system. Catecholamines are chemicals produced by nerve tissue, and include neurotransmitters and hormones. One well-known catecholamine hormone is adrenaline, also known as epinephrine.

While this hypothesis is still being investigated, the study authors present the idea that a potential mechanism for ADHD is via disruption of catecholamines, and probably via dopamine. Dopamine is among several neurotransmitters used by neuronal cells to regulate groups of neurons.

“Features reminiscent of ADHD”

Here's what the researchers did: Pregnant female mice were given oral doses of deltamethrin every three days. The doses chosen fell within a range that was lower than the “no observable adverse effect level” or NOAEL, which is used to set an allowable range for human exposure by EPA. The purpose of choosing this range of doses was to mimic common exposure levels in the population.

They then examined the offspring (exposed in utero) of these pregnant mice, using a number of markers of behavior and neurochemistry that are characteristics associated with ADHD.

So what did they find? Let me just say that the findings are not simple to explain. Among the results reported: exposure to deltamethrin during development resulted in increased dopamine transporter (DAT) levels in the brain, deficits in working memory and attention, and impulsive-like behaviors. These are “features reminiscent of ADHD.”

The authors flagged that the role DAT may play in ADHD is still controversial, since studies report conflicting results. What to make of this? We do know that mice that have the DAT “knocked out,” or not expressed, are hyperactive.

The authors' hypothesis for these conflicting results is that the differences may lie in variation in DAT expression in different regions of the brain, depending on the animal models used. Regardless, the researchers in this study did find an effect on DAT.

To top it all off, a little epidemiology…

NHANES data from 1999-2002 were used for this analysis. The researchers found that urinary pyrethroid metabolites were associated with increased risk of ADHD diagnosis, as reported by parents of the children surveyed in NHANES. 

Parents reported ADHD in 503, or 9.2% of the 5,849 children ages 6-15 who were included in the analysis from the NHANES survey. Of those 5,489, 2,123 of those children had pyrethroid pesticide urinary metabolite data that was used for this analysis.

A statistically significant association between pyrethroid metabolites found in urine and diagnosis of ADHD was found. This study was a case-control study, with the comparison being made between those children who had any detectable level of pyrethroid metabolites in their urine and those who did not.

I've learned from reading about epidemiology that establishing a direct cause for a given disease is very difficult. The science of epidemiology is about studying disease patterns in a population and determining whether or not a Potential Cause X is associated with Disease Y.

This area of study also directly translates into making informed policy decisions for preventing disease. When associations with increased risk are found, we should be listening very carefully.





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