This study will assess neurodevelopment and blood biomarkers in a cohort of 200 Latino migrant children and young people 12-24 years of age before and after the EPA revokes all tolerances for the heavily used organophosphate pesticide chlorpyrifos, slated for December 2016. This policy change creates a unique and time limited opportunity to collect baseline blood, urine and neurodevelopmental measures before the end of the 2016 growing season and again in the following year to test the general hypothesis that lower exposure to chlorpyrifos will improve neurodevelopmental endpoints in eastern stream Latino migrant children who work in agriculture or reside nearby. Here we propose a population-based case control study that will assess ADHD, ASD, and tremor, exposure to individual pesticides, herbicides, and heavy metals through urinary profiling, and blood gene expression signatures specific to high levels of chlorpyrifos to determine if reduced exposure to chlorpyrifos will improve neurodevelopmental endpoints and restore function in axonal guidance pathways.
Aim 1 will examine whether frequency of neurodevelopmental deficits, assayed by screens for ADHD, ASD and tremor, correlates with increased levels of specific urinary pesticide metabolites and metals. ADHD will be screened using the Conners 3-SR Scale in participants ages 12-17 and the Conners' Adult ADHD Rating Scale (CARRS)-SR will be used in participants ages 18-24. ASD will be scored using the Social Responsiveness Scale (SRS-2) in ages 18-24. Resting tremor will be scored using the Fahn-Tolosa-Marin Tremor Rating (FTM) Scale. Environmental exposures will be determined by levels of urinary pesticide metabolites for the organophosphates (chlorpyrifos, diazinon, malathion, parathion, pirimphos-methyl), pyrethroids, carbamates, herbicides (2,4-D, atrazine, glyphosate) and total metals including V, Cr, Mn, Fe, Cu, Zn, As, Se, Sr, Cd, Sn, Sb, Pb, and U. Reduced levels of chlorpyrifos and any compensatory increases in other pesticides will be confirmed in year 2 and association studies conducted between neurodevelopmental scores and levels of individual pesticides and metals.
Aim 2 will determine the relationship between neurodevelopmental deficits and differential expression in key genes of the axonal guidance pathway specific to farmwork and pesticide exposure which include EPHA2, EPHA7, EFNA3, EFNA4, SLA, MAPT, MAP4K4, and GNAS. Expression signatures will be correlated with levels of individual pesticides, herbicides and metals. Bayesian sparse factor regression approaches will model neurodevelopment scores, gene expression and exposure data. Our molecular epidemiological approach will allow association studies between scores on assessments for ADHD, ASD and tremor with blood-derived gene expression in the same cohort for the first time and will determine immediate impact of chlorpyrifos revocation on Latino migrant children's health.
Strategies to protect neurodevelopment in eastern stream Latino migrant children will be identified in a case control study that compares measures of neurodevelopment, molecular function in axonal guidance pathways and exposure to the widely used neurotoxic organophosphate pesticide chlorpyrifos, before and after all uses are canceled in late 2016. Neurodevelopmental screens for attention deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD), and tremor will be followed up with clinical diagnoses and treatment plans in this underserved population.
