Increased risk of attention‐deficit/hyperactivity disorder associated with exposure to organophosphate pesticide in Taiwanese children

Yu, Ching-Jung; Du, Jung‐Chieh; Chiou, Hsien-Chih; Chung, Ming Yi; Yang, Winnie; Chen, Y.-S.; Fuh, Ming‐Ren; Chien, Ling-Chu; Hwang, Betau; Chen, M.-L.

doi:10.1111/andr.12183

Cited by 77 publications

(39 citation statements)

References 75 publications

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“…In contrast to our findings, several previous studies have reported adverse associations between OPs and various measures of executive functioning, including attention, ADHD, and working memory (Bouchard et al, 2010, 2011; Eskenazi et al, 2014; Marks et al, 2010; Rauh et al, 2011, 2006; Yu et al, 2016), although studies examining prenatal exposure originate from only two other cohorts (Bouchard et al, 2011; Marks et al, 2010; Rauh et al, 2011). In the CHAMACOS cohort, Marks et al (Marks et al, 2010) reported associations between ΣDMPs and ΣDEPs and parent-report measures of attention problems at 3.5 but not 5 years, and also associations with a performance-based measure of attention, the Kiddie Connors Performance Test (K-CPT).…”

Section: Discussioncontrasting

confidence: 99%

Prenatal exposure to organophosphorus pesticides and childhood neurodevelopmental phenotypes

Furlong

Herring²,

Buckley

et al. 2017

Environmental Research

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Prenatal exposure to organophosphorus pesticides (OPs) has been associated with different neurodevelopmental outcomes across different cohorts. A phenotypic approach may address some of these differences by incorporating information across scales and accounting for the complex correlational structure of neurodevelopmental outcomes. Additionally, Bayesian hierarchical modeling can account for confounding by collinear co-exposures. We use this framework to examine associations between prenatal exposure to OPs and behavior, executive functioning, and IQ assessed at age 6–9 years in a cohort of 404 mother/infant pairs recruited during pregnancy. We derived phenotypes of neurodevelopment with a factor analysis, and estimated associations between OP metabolites and these phenotypes in Bayesian hierarchical models for exposure mixtures. We report seven factors: 1) Impulsivity and Externalizing, 2) Executive Functioning, 3) Internalizing, 4) Perceptual Reasoning, 5) Adaptability, 6) Processing Speed, and 7) Verbal Intelligence. These, along with the Working Memory Index, were standardized and scaled so that positive values reflected positive attributes and negative values represented adverse outcomes. Standardized dimethylphosphate metabolites were negatively associated with Internalizing factor scores ( trueβ^−0.13, 95% CI − 0.26, 0.00) but positively associated with Executive Functioning factor scores ( trueβ^0.2em0.18, 95% CI 0.04, 0.31). Standardized diethylphosphate metabolites were negatively associated with the Working Memory Index ( trueβ^−0.17, 95% CI − 0.33, − 0.03). Associations with factor scores were generally stronger and more precise than associations with individual instrument-specific items. Factor analysis of outcomes may provide some advantages in etiological studies of childhood neurodevelopment by incorporating information across scales to reduce dimensionality and improve precision.

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Section: Discussioncontrasting

confidence: 99%

Prenatal exposure to organophosphorus pesticides and childhood neurodevelopmental phenotypes

Furlong

Herring²,

Buckley

et al. 2017

Environmental Research

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“…The level of dimethyl phosphate was significantly higher in the children with ADHD compared to controls. 48 Of note, this study measured concurrent pesticide levels, and while the design is case-control, there is no assurance that the concurrent pesticide levels are similar to pesticide levels during critical periods of development. A retrospective cohort study examined associations between ADHD and home residence near several environmental exposures.…”

Section: Role Of Genetics and The Environment And Genetics In Neurocomentioning

confidence: 98%

Children’s low-level pesticide exposure and associations with autism and ADHD: a review

2018

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Pesticides are chemicals that are designed specifically for the purpose of killing or suppressing another living organism. Human toxicity is possible with any pesticide, and a growing body of literature has investigated possible associations with neurodevelopmental disorders. Attention deficit disorder with or without hyperactivity (ADHD) and autism spectrum disorder (ASD) are two of these specific disorders that have garnered particular interest. Exposure to toxic chemicals during critical windows of brain development is a biologically plausible mechanism. This review describes the basic laboratory science including controlled pesticide dosing experiments in animals that supports a mechanistic relationship in the development of ADHD and/or ASD. Epidemiological relationships are also described for low-level pesticide exposure and ADHD and/or ASD. The available evidence supports the hypothesis that pesticide exposure at levels that do not cause acute toxicity may be among the multifactorial causes of ADHD and ASD, though further study is needed, especially for some of the newer pesticides.

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“…For other SNPs: rs7395429, rs3758653, rs11246228, rs752306 [49][50][51] ; rs4646984 52 ; rs916457 53 ; rs936465 54 , nometa-analyses can be performed, because very few studies were available (minimum three studies), considering that Yu and colleagues 49,50 and Chang and colleagues 51 studied the same population.…”

Section: Newcastle-ottawa Scalementioning

confidence: 99%

DRD4 48 bp multiallelic variants as age-population-specific biomarkers in attention-deficit/hyperactivity disorder

et al. 2020

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The identification of biomarkers to support the diagnosis and prediction of treatment response for attention-deficit/ hyperactivity disorder (ADHD) is still a challenge. Our previous works highlighted the DRD4 (dopamine receptor D4) as the best potential genetic marker for childhood diagnosis and methylphenidate (MPH) response. Here, we aimed to provide additional evidence on biomarkers for ADHD diagnosis and treatment response, by using more specific approaches such as meta-analytic and bioinformatics tools. Via meta-analytic approaches including over 3000 cases and 16,000 controls, we demonstrated that, among the different variants studied in DRD4 gene, the 48-base pair, Variable Tandem Repeat Polymorphism, VNTR in exon 3 showed an age/population-specificity and an allelic heterogeneity. In particular, the 7R/"long" allele was identified as an ADHD risk factor in European-Caucasian populations (d = 1.31, 95%CI: 1.17-1.47, Z = 4.70/d = 1.36, 95%CI: 1.20-1.55, Z = 4.78, respectively), also, from the results of last meta-analysis, linked to the poor MPH efficacy. The 4R/"short" allele was a protective factor in European-Caucasian and South American populations (d = 0.83, 95%CI: 0.75-0.92, Z = 3.58), and was also associated to positive MPH response. These results refer to children with ADHD. No evidence of such associations was detected for adults with persistent ADHD (data from the last meta-analysis). Moreover, we found evidence that the 4R allele leads to higher receptor expression and increased sensitivity to dopamine, as compared with the 7R allele (d = 1.20, 95%CI: 0.71-1.69, Z = 4.81), and this is consistent with the ADHD protection/susceptibility effects of the respective alleles. Using bioinformatics tools, based on the latest genome-wide association (GWAS) meta-analysis of the Psychiatry Genomic Consortium (PGC), we demonstrated that the 48 bp VNTR is not in Linkage Disequilibrium with the DRD4 SNPs (Single Nucleotide Polymorphisms), which were not found to be associated with ADHD. Moreover, a DRD4 expression downregulation was found in ADHD specific brain regions (Putamen, Z score = −3.02, P = 0.00252). Overall, our results suggest that DRD4 48 bp VNTR variants should be considered as biomarkers to support the diagnosis of ADHD and to predict MPH response, although the accuracy of such a biomarker remains to be further elucidated.

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Increased risk of attention‐deficit/hyperactivity disorder associated with exposure to organophosphate pesticide in Taiwanese children

Cited by 77 publications

References 75 publications

Prenatal exposure to organophosphorus pesticides and childhood neurodevelopmental phenotypes

Prenatal exposure to organophosphorus pesticides and childhood neurodevelopmental phenotypes

Children’s low-level pesticide exposure and associations with autism and ADHD: a review

DRD4 48 bp multiallelic variants as age-population-specific biomarkers in attention-deficit/hyperactivity disorder

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