Associations of Acetylcholinesterase Inhibition Between Pesticide Spray Seasons with Depression and Anxiety Symptoms in Adolescents, and the Role of Sex and Adrenal Hormones on Gender Moderation

Cholinesterase inhibitor pesticides, especially organophosphates, are endocrine disruptors and a few existing studies have linked self-reports of exposure with increased depression and anxiety. Some evidence suggests that associations may be stronger in women, but the mechanism of this gender difference is unclear. We assessed whether acetylcholinesterase (AChE) inhibition between 2 time points (reflecting greater cholinesterase inhibitor exposure) during different agricultural seasons in the year was associated with anxiety/depression symptoms. We examined 300 adolescents (ages 11–17 years, 51% female) living near agricultural settings in Ecuador (ESPINA study) twice in 2016: April and July–October. We assessed AChE activity (finger stick), estradiol, testosterone, dehydroepiandrosterone, cortisol (saliva) and anxiety and depression scales (CDI-2 and MASC-2). The mean (SD) depression and anxiety scores were 52.8 (9.3) and 58.1 (9.6), respectively. The median (25th, 75th percentile) AChE change (July–October vs April) was − 3.94% (− 10.45%, 5.13%). For every 10% decrease in AChE activity, there was a 0.96 unit (95% CI 0.01, 1.90) increase in depression symptoms and an OR of elevated depression score of 1.67 (1.04, 2.66). These associations were stronger in girls (OR = 2.72 [1.23, 6.00]) than boys (1.18 [0.59, 2.37]). Adjustment for cortisol, testosterone and dehydroepiandrosterone reduced gender differences by 18–62%. No associations were observed with anxiety. Inhibition of AChE activity at 2 points in time during different pesticide spray periods was associated with greater depression symptoms, affecting girls more than boys. Gender differences may be partly explained by endocrine disruption. These findings suggest that AChE inhibition may transiently affect the mood of adolescents.