Glyphosate Use Predicts ADHD Hospital Discharges in the Healthcare Cost and Utilization Project Net (HCUPnet): A Two-Way Fixed-Effects Analysis

Abstract

There has been considerable international study on the etiology of rising mental disorders, such as attention-deficit hyperactivity disorder (ADHD), in human populations. As glyphosate is the most commonly used herbicide in the world, we sought to test the hypothesis that glyphosate use in agriculture may be a contributing environmental factor to the rise of ADHD in human populations. State estimates for glyphosate use and nitrogen fertilizer use were obtained from the U.S. Geological Survey (USGS). We queried the Healthcare Cost and Utilization Project net (HCUPNET) for state-level hospitalization discharge data in all patients for all-listed ADHD from 2007 to 2010. We used rural-urban continuum codes from the USDA-Economic Research Service when exploring the effect of urbanization on the relationship between herbicide use and ADHD. Least squares dummy variable (LSDV) method and within method using two-way fixed effects was used to elucidate the relationship between glyphosate use and all-listed ADHD hospital discharges. We show that a one kilogram increase in glyphosate use, in particular, in one year significantly positively predicts state-level all-listed ADHD discharges, expressed as a percent of total mental disorders, the following year (coefficient = 5.54E-08, p<.01). A study on the effect of urbanization on the relationship between glyphosate and ADHD indicates that the relationship is marginally significantly positive after multiple comparison correction only in urban U.S. counties (p<.025). Furthermore, total glyphosate use is strongly positively associated with total farm use of nitrogen fertilizers from 1992 to 2006 (p<.001). We present evidence from the biomedical research literature of a plausible link among glyphosate, nitrogen dysbiosis and ADHD. Glyphosate use is a significant predictor of state hospitalizations for all-listed ADHD hospital discharges, with the effect concentrated in urban U.S. counties. This effect is seen even after controlling for individual state characteristics, strong correlations over time, and other significant associations with ADHD in the literature. We draw upon the econometric results to propose unique mechanisms, borrowing principles from soil and atmospheric sciences, for how glyphosate-based herbicides may be contributing to the rise of ADHD in all populations.

Brain Disorders and Chemical Pollutants: A Gap Junction Link?

“…Additional studies also reported a particular role of exposure to the agricultural and combustion pollutant, nitrous oxide (N 2 O), which might be a primary environmental trigger in the onset of not only ADHD but also of other neurodevelopmental disorders, such as ASD. On this particular aspect of agricultural pollutants, glyphosate could also be a factor responsible for ADHD [ 413 ].…”

Editors must be vigilant to guarantee the quality and credibility of published scientific work

“…Unfortunately, editors seem often unaware of the problem that more and more non-scientists try to publish allegedly scientific studies in scientific journals. In this context, a mistakenly published study is noteworthy that linked the most commonly used herbicide glyphosate to the rise of ADHD (Fluegge and Fluegge 2015). This paper was rejected after peer review and consultation with the editorial board of PLoS ONE (The PLoS ONE staff 2015).…”

The possible role of air pollution in the link between ADHD and obesity

“…bodies of water) in southern Minnesota (USA) have reported levels that are significantly higher than established Intergovernmental Panel on Climate Change estimates [7], suggesting that a more comprehensive reevaluation of environmental N 2 O burden is warranted. Interestingly, obesity rates are climbing significantly in states with large agricultural operations [9], and perhaps more importantly, a recent epidemiological study on ADHD (case discernment derived from inpatient psychiatric evaluation, and therefore representing possible 'severe' ADHD) indicated that the highest ADHD prevalence occurred in the states of Nebraska and Minnesota [10,11].…”

“…In accord with the literature identifying ADHD symptoms in children exposed to general anesthesia for surgery [12], it has been proposed that increasing exposure to environmental N 2 O-most especially in light of a marked reduction in other air pollutants [13]-may be the principal exposure contributing to ADHD and other neurodevelopmental pathologies, like autism spectrum disorders (ASD). [10,11,14,15] Through targeting several neural substrates, including those of the opioidergic, cholinergic, dopaminergic, and glutamatergic systems, this exposure may cumulatively induce a chronic parasympathetic state in those exposed [15], as has been shown in healthy humans exposed to inhalational N 2 O [16]. Given that environmentally relevant concentrations (i.e.…”

“…However, exposure to N 2 O may target dopaminergic activity through possible impairment of dopamine receptor 4 (DR4) via N 2 O-mediated inhibition of methionine synthase [10,11]. DR4 is a receptor that has been implicated in ADHD [38].…”