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Gestational Exposure to Organophosphate Pesticides and Longitudinally Assessed Behaviors Related to Attention-Deficit/Hyperactivity Disorder and Executive Function.

ABSTRACT: The brain's prefrontal cortex directs higher-order cognitive and behavioral processes that are important for attention, working memory, and inhibitory control. We investigated whether gestational exposure to organophosphate (OP) pesticides was associated with these abilities in childhood and early adolescence. Between 1999 and 2000, we enrolled pregnant women in a birth cohort drawn from an agricultural region of California. We measured dialkyl phosphate (DAP) metabolites of OP pesticides in maternal pregnancy urine samples (13 and 26 weeks) and estimated associations with behaviors related to attention-deficit/hyperactivity disorder and executive function, assessed longitudinally; 351 families provided neurodevelopmental outcome data at any point when the child was aged 7-12 years. We assessed function across multiple dimensions (e.g., working memory, attention), methods (e.g., behavior reports, child assessment), and reporters (e.g., mothers, teachers, child self-reports). Higher gestational DAP concentrations were consistently associated with behaviors related to attention-deficit/hyperactivity disorder and executive function. For example, a 10-fold increase in gestational DAP concentration was associated with poorer longitudinally assessed Behavior Rating Inventory of Executive Function scores, as reported by mothers (β = 4.0 (95% confidence interval: 2.1, 5.8); a higher score indicates more problems), and Weschler Intelligence Scale for Children-Fourth Edition Working Memory scores (a 3.8-point reduction; β = -3.8 (95% confidence interval: -6.2, -1.3)). Reducing gestational exposure to OP pesticides through public health policy is an important goal.

SUBMITTER: Sagiv SK

PROVIDER: S-EPMC8757311 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BACKGROUND:There are suggestions that patients with attention-deficit/hyperactivity disorder (ADHD) show impairment in executive attention control and emotion regulation. This study investigated emotion regulation as a function of the recruitment of executive attention in patients with ADHD. METHODS:Thirty-five healthy children/adolescents (mean age = 13.91) and twenty-six children/adolescents with ADHD (mean age = 14.53) participated in this fMRI study. They completed the affective Stroop paradigm viewing positive, neutral and negative images under varying cognitive loads. A 3-way ANOVA (diagnosis-by-condition-by-emotion) was conducted on the BOLD response data. Following this, 2 3-way ANOVAs (diagnosis-by-condition-by-emotion) were applied to context-dependent psychophysiological interaction (gPPI) analyses generated from a dorsomedial frontal cortex and an amygdala seed (identified from the BOLD response ANOVA main effects of condition and emotion respectively). RESULTS:A diagnosis-by-condition interaction within dorsomedial frontal cortex revealed reduced recruitment of dorsomedial frontal cortex as a function of increased task demands in the children/adolescents with ADHD relative to healthy children/adolescents. The level of reduction in recruitment of dorsomedial frontal cortex was significantly correlated with symptom severity (total and hyperactivity) measured by Conner's Parent Report Scale in the children/adolescents with ADHD. In addition, analysis of gPPI data from a dorsomedial frontal cortex seed revealed significant diagnosis-by-condition interactions within lateral frontal cortex; connectivity between dorsomedial frontal cortex and lateral frontal cortex was reduced in the patients with ADHD relative to comparison youth during congruent and incongruent task trials relative to view trials. There were no interactions of group, or main effect of group, within the amygdala in the BOLD response ANOVA (though children/adolescents with ADHD showed increased responses to positive images within temporal cortical regions during task trials; identified by the diagnosis-by-condition-by-emotion interaction). However, analysis of gPPI data from an amygdala seed revealed decreased connectivity between amygdala and lentiform nucleus in the presence of emotional stimuli in children/adolescents with ADHD (diagnosis-by-emotion interaction). CONCLUSION:The current study demonstrated disrupted recruitment of regions implicated in executive function and impaired connectivity within those regions in children/adolescents with ADHD. There were also indications of heightened representation of emotional stimuli in patients with ADHD. However, as the findings were specific for positive stimuli, the suggestion of a general failure in emotion regulation in ADHD was not supported.

Project description:BackgroundA growing body of literature investigated childhood exposure to environmental chemicals in association with attention-deficit/hyperactivity disorder (ADHD) symptoms, but limited studies considered urinary mixtures of multiple chemical classes. This study examined associations of concurrent exposure to non-persistent chemicals with ADHD symptoms in children diagnosed with autism spectrum disorder (ASD), developmental delay (DD), and typical development (TD).MethodsA total of 549 children aged 2-5 years from the Childhood Autism Risks from Genetics and Environment (CHARGE) case-control study were administered the Aberrant Behavior Checklist (ABC). This study focused on the ADHD/noncompliance subscale and its two subdomains (hyperactivity/impulsivity, inattention). Sixty-two chemicals from four classes (phenols/parabens, phthalates, organophosphate pesticides, trace elements) were quantified in child urine samples, and 43 chemicals detected in > 70% samples were used to investigate their associations with ADHD symptoms. Negative binomial regression was used for single-chemical analysis, and weighted quantile sum regression with repeated holdout validation was applied for mixture analysis for each chemical class and all chemicals. The mixture analyses were further stratified by diagnostic group.ResultsA phthalate metabolite mixture was associated with higher ADHD/noncompliance scores (median count ratio [CR] = 1.10; 2.5th, 97.5th percentile: 1.00, 1.21), especially hyperactivity/impulsivity (median CR = 1.09; 2.5th, 97.5th percentile: 1.00, 1.25). The possible contributors to these mixture effects were di-2-ethylhexyl phthalate (DEHP) metabolites and mono-2-heptyl phthalate (MHPP). These associations were likely driven by children with ASD as these were observed among children with ASD, but not among TD or those with DD. Additionally, among children with ASD, a mixture of all chemicals was associated with ADHD/noncompliance and hyperactivity/impulsivity, and possible contributors were 3,4-dihydroxy benzoic acid, DEHP metabolites, MHPP, mono-n-butyl phthalate, and cadmium.ConclusionsEarly childhood exposure to a phthalate mixture was associated with ADHD symptoms, particularly among children with ASD. While the diverse diagnostic profiles limited generalizability, our findings suggest a potential link between phthalate exposure and the comorbidity of ASD and ADHD.

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Gestational Exposure to Organophosphate Pesticides and Longitudinally Assessed Behaviors Related to Attention-Deficit/Hyperactivity Disorder and Executive Function.

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