According to a new study in Pediatrics, there might be a relationship between exposure to certain pesticides and ADHD. The study found that children who had a higher level of organophosphate pesticide by-products in their urine were significantly more likely to have a diagnosis of ADHD.
The study is freely available, so if you are interested I suggest you read it from yourself.
The first question that came to mind when I read this study is exactly what is an organophosphate pesticide. An organophosphate pesticide is a type of insecticide that is widely used in agriculture, the home, gardens, an veterinary practice. These pesticides work by disrupting the normal function of the nervous system and affect people as well as insects (some organophosphates were used in World War II as nerve agents). However, these chemicals do not persist for long in the environment so are thought to be safer than the chemicals that they replaced (such as DDT).
In this study there were a total of 1,139 children between the ages of 8 and 15. Of these children, 119 met strict criteria for ADHD while an additional 30 children did not currently met the criteria but were on medications for ADHD. Since ADHD, like autism, is behavioral based diagnosis you need to consider those children whose behaviors are currently being controlled by medication and don't currently appear to have ADHD. The prevalence of ADHD in these children was about 12.1% percent which is slightly higher than the national average but isn't too far out of line.
Think about that number for a minute - one out of every ten children has a form of ADHD. You may be one of those people who think that this diagnosis is overused or that this is just an excuse for misbehaving children, and I am sure that there is some of that going on. But ADHD, like autism, is a large problem in this country and awareness and/or other social factors cannot account for the scope and magnitude of the growth.
All of the children in the study had a urine sample collected and these samples were analyzed to try to determine exposure to a organophosphate pesticides. Since these chemicals are broken down by the body, the researchers could not directly measure the exposure level in the urine. Instead the researchers looked at the levels of 6 different metabolites (by-products). The majority of children (94%) had a detectable level of at least one of the metabolites, meaning that the majority had at least some exposure to these pesticides.
The researchers found that children with a higher levels of these metabolites had a greatly increased chance of having ADHD, even after taking into account gender, race, income level, body mass index (BMI), blood lead level, maternal age at birth, and maternal smoking during pregnancy. The exact risks varied from depending on the metabolite in question and varied from a low of 20% greater chance (odds ratio 1.21) all the way to a 100% greater chance (odds ratio 2.09).
The interesting thing to me is that these children had what would be considered an "average" level of exposure to these pesticides. The majority of the exposure in these children is thought to be from dietary sources and residential usage. Or in other words, most children in the US would have a similar level of exposure.
On the flip side, there are some potential problems with the study.
The result is based on a single urine sample and measures exposure at a specific point in time. Since these chemicals are thought to be cleared from the body in a matter of days, this sample would only measure short term exposure and does not mean that the at-risk children had a continuing higher exposure.
The other problem is that this study does not establish what the nature of the relationship is - it does not say that higher exposure to pesticides causes ADHD. It is possible that children with ADHD have behaviors that give them a higher exposure, perhaps by favoring a certain type of food. Or perhaps the relationship is just a fluke of the data set.
Regardless, this is definitely something that needs to be researched further.
References
1: Bouchard MF, Bellinger DC, Wright RO, Weisskopf MG.
Attention-Deficit/Hyperactivity Disorder and Urinary Metabolites of Organophosphate Pesticides. Pediatrics. 2010 May 17. [Epub ahead of print] PubMed PMID: 20478945.
Study text
Hi MJ
ReplyDeleteThis manuscript is totally related to how susceptible individuals may have problems with the metabolisms of xenobiotics, here OPs..
Psychiatry Res. 2010 May 18.
Decreased serum arylesterase activity in autism spectrum disorders.
Gaita L, Manzi B, Sacco R, Lintas C, Altieri L, Lombardi F, Pawlowski TL, Redman M, Craig DW, Huentelman MJ, Ober-Reynolds S, Brautigam S, Melmed R, Smith CJ, Marsillach J, Camps J, Curatolo P, Persico AM.
Laboratory of Molecular Psychiatry and Neurogenetics, University Campus Bio-Medico, Rome, Italy; Department of Experimental Neurosciences, IRCCS "Fondazione Santa Lucia", Rome, Italy.
Abstract
The PON1 gene, previously found associated with autism spectrum disorders (ASDs), encodes a serum protein responsible for the detoxification of organophosphates (OPs) and able to exert several enzymatic activities. PON1 arylesterase, but not diazoxonase activity, was significantly decreased in 174 ASD patients compared to 175 first-degree relatives and 144 controls (P=2.65x10(-)(16)). First degree relatives displayed intermediate activities, closer to patient than to control levels. Differences between patients, first-degree relatives and controls were especially evident among 164 Italians compared to 329 Caucasian-Americans, because arylesterase activity was significantly higher in Italian controls, compared to Caucasian-American controls (P=2.84x10(-)(16)). Arylesterase activity and PON protein concentrations were not significantly correlated, supporting a functional inhibition of arylesterase activity in ASD patients over quantitative changes in protein amounts. Serum arylesterase activity, in combination with PON1 genotypes at two single nucleotide polymorphisms (SNPs) known to influence protein amounts (rs705379: C-108T) and substrate specificity (rs662: Q192R), was able to discriminate ASD patients from controls with elevated sensitivity and specificity, depending on genotype and ethnic group. Serum arylesterase activity and genotyping at these two SNPs could thus represent an informative biochemical/genetic test, able to aid clinicians in estimating autism risk in ethnic groups with higher baseline arylesterase activity levels.
And more
ReplyDeleteJ Cell Mol Med. 2010 Mar;14(3):600-7. Epub 2009 Jun 28.
Paraoxonase 1 activities and polymorphisms in autism spectrum disorders.
Paşca SP et al
Department of Medical Biochemistry, Faculty of Medicine, Iuliu HaTieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania.
... Recent studies suggested a possible implication of the high-density lipoprotein associated esterase/lactonase paraoxonase 1 (PON1) in ASD. In the present study, we aimed at investigating the PON1 status in a group of 50 children with ASD as compared to healthy age and sex matched control participants. We evaluated PON1 bioavailability (i.e. arylesterase activity) and catalytic activity (i.e. paraoxonase activity) in plasma using spectrophotometric methods and the two common polymorphisms in the PON1 coding region (Q192R, L55M) by employing Light Cycler real-time PCR. We found that both PON1 arylesterase and PON1 paraoxonase activities were decreased in autistic patients (respectively, P < 0.001, P < 0.05), but no association with less active variants of the PON1 gene was found. The PON1 phenotype, inferred from the two-dimensional enzyme analysis, had a similar distribution in the ASD group and the control group. In conclusion, both the bioavailability and the catalytic activity of PON1 are impaired in ASD, despite no association with the Q192R and L55M polymorphisms in the PON1 gene and a normal distribution of the PON1 phenotype.
Biomarkers. 2003 Jan-Feb;8(1):1-12.
Paraoxonase (PON 1) as a biomarker of susceptibility for organophosphate toxicity.
Costa LG, Richter RJ, Li WF, Cole T, Guizzetti M, Furlong CE.
Paraoxonase (PON1) is an A-esterase capable of hydrolysing the active metabolites (oxons) of a number of organophosphorus (OP) insecticides such as parathion, diazinon and chlorpyrifos. PON1 activity is highest in liver and plasma, and among animal species significant differences exist, with birds and rabbits displaying very low and high activity, respectively. Human PON1 has two polymorphisms in the coding region (Q192R and L55M) and five polymorphisms in the promoter region. The Q192R polymorphism imparts different catalytic activity toward some OP substrates, while the polymorphism at position -108 (C/T) is the major contributor to differences in the level of PON1 expression. Animal studies have shown that PON1 is an important determinant of OP toxicity, with animal species with a low PON1 activity having an increased sensitivity to OPs. Administration of exogenous PON1 to rats or mice protects them from the toxicity of OPs. PON1 knockout mice display a high sensitivity to the toxicity of diazoxon and chlorpyrifos oxon, but not paraoxon. In vitro assayed catalytic efficiencies of purified PON(192) isoforms for hydrolysis of specific oxon substrates accurately predict the degree of in vivo protection afforded by each isoform. Low PON1 activity may also contribute to the higher sensitivity of newborns to OP toxicity.
AND the role of xenobiotics management genetics in ASD has been presented at least since 5 years ago
J Child Neurol. 2004 Jun;19(6):413-7.
Polymorphisms in xenobiotic metabolism genes and autism.
Serajee FJ, Nabi R, Zhong H, Huq M.
... We performed family-based association studies of polymorphisms in metal-regulatory transcription factor 1(MTF1), a multispecific organic anion transporter (ABCC1), proton-coupled divalent metal ion transporters (SLC11A3 and SLC11A2), paraoxonase 1 (PON1), and glutathione S-transferase (GSTP1) genes in 196 autistic disorder families. There was deviation from the expected pattern of transmission for polymorphisms in MTF1 (Single nucleotide polymorphism database reference identification number, dbSNP rs3790625, P = .02) and divalent metal ion transporter SLC11A3 (dbSNP rs2304704, P = .07) genes. Although these results might represent chance finding, further investigations of genetic variations of metal metabolism in autism are warranted.
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ReplyDeleteThanks Maria, I will have to take a look at these.
ReplyDeleteWell, the methodological controls leave a lot to be desired. Regardless, I thought it was an interesting study. Let's see where replication takes us.
ReplyDeleteAlso, if it does turn out that pesticides caused (are a cause of) ADHD, are we going to start blaming Big farma?
Interverbal,
ReplyDeleteWhere do you think the controls were lacking? I didn't see anything that immediately jumped out at me, but then again, I wasn't looking as closely at that level of details.
As for what we do if it turns out there is a relation, well, I think we (attempt to) ban this type of chemical and replace it with a (safer) alternative. I don't think we need to blame the chemical companies for it.
I do see a few areas bias could creep in.
ReplyDelete-Utilized a survey based executive database that may be open to random and systematic statistical errors (in my experience they often are).
-Parent based interview used as diagnostic ascertainment (reliability and validity checks for this procedure?)
-Not sure how they did their adjustment statistics. This is not so much a problem as it is a point of inquiry.
That being said, I am cautious about this study, but not necessarily unfriendly to it. I would expect higher quality replications in the future though.
As far as Big Farma, meh… just hunting for a bad pun.
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