Exposure to non-persistent pesticides, BDNF, and behavioral function in adolescent males: Exploring a novel effect biomarker approach
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AuthorRodríguez Carrillo, Andrea; Mustieles Miralles, Vicente; Suárez, Beatriz; Peinado, Francisco; Artacho Cordón, Francisco; López García, Luis Carlos; Arrebola Moreno, Juan Pedro; Olea Serrano, Nicolás; Fernández Cabrera, Mariana Fátima; Freire, Carmen
BDNFNon-persistent pesticidesHBM4EUBehaviorEffect biomarkersAdolescents
Andrea Rodríguez-Carrillo... [et al.]. Exposure to non-persistent pesticides, BDNF, and behavioral function in adolescent males: Exploring a novel effect biomarker approach, Environmental Research, Volume 211, 2022, 113115, ISSN 0013-9351, [https://doi.org/10.1016/j.envres.2022.113115]
SponsorshipEuropean Union's Horizon 2020 research and innovation program HBM4EU 733032; Instituto de Salud Carlos III CP16/00085 FIS 17/01526; Human Genotyping Laboratory at the Spanish National Cancer Research Center (CeGen-PRB3); Biomedical Research Networking Center-CIBER de Epidemiologia y Salud Publica (CIBERESP); University of Granada UCE-PP2017-06; Spanish Government FPU 16/03011; Miguel Servet Type I program of the ISCIII "Fondo Europeo de Desarrollo Regional" (ISCIII/FEDER) MS16/00085
Background: Numerous contemporary non-persistent pesticides may elicit neurodevelopmental impairments. Brain-derived neurotrophic factor (BDNF) has been proposed as a novel effect biomarker of neurological function that could help to understand the biological responses of some environmental exposures. Objectives: To investigate the relationship between exposure to various non-persistent pesticides, BDNF, and behavioral functioning among adolescents. Methods: The concentrations of organophosphate (OP) insecticide metabolites 3,5,6-trichloro-2-pyridinol (TCPy), 2-isopropyl-4-methyl-6-hydroxypyrimidine (IMPy), malathion diacid (MDA), and diethyl thiophosphate (DETP); metabolites of pyrethroids 3-phenoxybenzoic acid (3-PBA) and dimethylcyclopropane carboxylic acid (DCCA), the metabolite of insecticide carbaryl 1-naphthol (1-N), and the metabolite of ethylene-bis-dithiocarbamate fungicides ethylene thiourea (ETU) were measured in spot urine samples, as well as serum BDNF protein levels and blood DNA methylation of Exon IV of BDNF gene in 15–17-year-old boys from the INMA-Granada cohort in Spain. Adolescents’ behavior was reported by parents using the Child Behavior Check List (CBCL/ 6–18). This study included 140 adolescents of whom 118 had data on BDNF gene DNA methylation. Multivariable linear regression, weighted quantile sum (WQS) for mixture effects, and mediation models were fit. Results: IMPy, MDA, DCCA, and ETU were detected in more than 70% of urine samples, DETP in 53%, and TCPy, 3-PBA, and 1-N in less than 50% of samples. Higher levels of IMPy, TCPy, and ETU were significantly associated with more behavioral problems as social, thought problems, and rule-breaking symptoms. IMPy, MDA, DETP, and 1-N were significantly associated with decreased serum BDNF levels, while MDA, 3-PBA, and ETU were associated with higher DNA methylation percentages at several CpGs. WQS models suggest a mixture effect on more behavioral problems and BDNF DNA methylation at several CpGs. A mediated effect of serum BDNF within IMPy-thought and IMPy-rule breaking associations was suggested. Conclusion: BDNF biomarkers measured at different levels of biological complexity provided novel information regarding the potential disruption of behavioral function due to contemporary pesticides, highlighting exposure to diazinon (IMPy) and the combined effect of IMPy, MDA, DCCA, and ETU. However, further research is warranted.