Glyphosate Use Predicts Healthcare Utilization for ADHD 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 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 increase in healthcare utilization among individuals with diagnosed ADHD.State estimates for glyphosate use and nitrogen fertilizer use were obtained from the USGS. We queried the Healthcare Cost and Utilization Project net (HCUPNET) for state-level hospitalization discharge diagnosis data on all patients for all-listed ADHD cases from 2007 to 2010. The least squares dummy variable (LSDV) method and within the method using two-way fixed effects was used to elucidate the relationship between glyphosate use and all-listed ADHD hospital discharge diagnoses.A 1-kg increase in glyphosate use in one year positively predicts state-level all-listed ADHD discharge diagnoses the following year (coefficient = 5.54E-08, p<.01). A study of the effects of urbanization on the relationship between glyphosate use and ADHD indicates that the relationship is marginally significantly positive in urban U.S. counties (p<.025). Furthermore, total glyphosate use is strongly associated with total farm use of nitrogen fertilizers from 1992 to 2006 (p<.001).Glyphosate use is a significant predictor of state healthcare utilization for ADHD, with the effect concentrated in urban U.S. counties. We draw upon the econometric results to propose unique and exploratory mechanisms, borrowing principles from soil and atmospheric sciences, for how glyphosate-based herbicides may be contributing to the rise of ADHD in all populations.

Air pollution and risk of hospitalization for epilepsy: the role of farm use of nitrogen fertilizers and emissions of the agricultural air pollutant, nitrous oxide

“…We rationalize this hypothesis by emphasizing prior clinical reports and animal studies indicating a N 2 O-induced suppression of epileptiform activity. Coupled with our prior conclusions, this hypothesis, if supported, may support the co-morbid link between epilepsy and other neurodevelopmental disorders by suggesting both are related to exposure to (i.e., ADHD and ASD) or withdrawal from (i.e., epilepsy) environmental N 2 O 6,7,8,9,17 .…”

“…For years 1997 to 2006, inclusive, we have gathered data on the state sum totals of farm use of nitrogen fertilizers (in kilograms) 20 , described in the authors' prior epidemiological studies 7,9 . Although the United States Geological Survey of the U.S. Department of the Interior states that "no warranty expressed or implied is made by the U.S. Geological Survey as to the accuracy of the data, " we believe the use of county data on a state aggregated level is consistent with the recommendations of the United States Geological Survey 20,21 .…”

“…Moreover, other government agencies, like the Environmental Protection Agency, make similar disclaimers regarding data contained on their organization's website . Our dependent condition of interest is hospitalization for both all-listed and principal diagnoses of epilepsy, derived from data using the Healthcare Cost and Utilization Project (HCUPnet) 25 , as has been performed previously 7,9 . We conducted a Poisson regression methodology including two-way fixed effects.…”

“…Increasing x k by one log-unit multiplies the mean by a factor exp{b 1k }. All regression analyses and related diagnostics were performed using R (packages ggplot2 and sandwich with robust standard errors), as we have described previously 7,9 . Although we are unable to directly replicate the methodology of Cakmak et al 2 , we believe the strength of our two-way fixed effects Poisson statistical approach lies in the fact that we have both accounted for individual state-level heterogeneity among a greater number of locations (30 selected HCUP states versus seven Chilean urban centers) and controlled for correlations across a longer time…”

“…One specific recommendation made by the expert panel was to incorporate aspects of climate change in the future study of the human health effects of air pollution. Consistent with these stated goals, we have recently proposed, through empirical investigation and review, that exposure to air pollution and specifically the pervasive air pollutant and greenhouse gas, nitrous oxide (N 2 O), may provoke susceptibility to neurodevelopmental disorders, like attention-deficit hyperactivity disorder (ADHD) and autism spectrum disorders (ASD) 6,7,8,9 . Epilepsy is a recognized comorbidity in both ADHD and ASD 10,11,12 .…”