A Research Strategy to Discover the Environmental Causes of Autism and Neurodevelopmental Disabilities

Abstract

Vol. 120, No. 7 EditorialOpen AccessA Research Strategy to Discover the Environmental Causes of Autism and Neurodevelopmental Disabilitiesis accompanied byPrenatal Exposure to PBDEs and NeurodevelopmentResidential Proximity to Freeways and Autism in the CHARGE StudyEnvironmental Chemicals in Pregnant Women in the United States: NHANES 2003–2004Manganese Exposure from Drinking Water and Children’s Classroom Behavior in BangladeshSerum Perfluorinated Compound Concentration and Attention Deficit/Hyperactivity Disorder in Children 5–18 Years of Age Philip J. Landrigan, Luca Lambertini, and Linda S. Birnbaum Philip J. Landrigan Search for more papers by this author , Luca Lambertini Search for more papers by this author , and Linda S. Birnbaum Search for more papers by this author Published:1 July 2012https://doi.org/10.1289/ehp.1104285Cited by:163AboutSectionsPDF ToolsDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InReddit Autism, attention deficit/hyperactivity disorder (ADHD), mental retardation, dyslexia, and other biologically based disorders of brain development affect between 400,000 and 600,000 of the 4 million children born in the United States each year. The Centers for Disease Control and Prevention (CDC) has reported that autism spectrum disorder (ASD) now affects 1.13% (1 of 88) of American children (CDC 2012) and ADHD affects 14% (CDC 2005; Pastor and Reuben 2008). Treatment of these disorders is difficult; the disabilities they cause can last lifelong, and they are devastating to families. In addition, these disorders place enormous economic burdens on society (Trasande and Liu 2011).Although discovery research to identify the potentially preventable causes of neuro-develop-mental disorders (NDDs) has increased in recent years, more research is urgently needed. This research encompasses both genetic and environ-mental studies.Genetic research has received particular investment and attention (Autism Genome Project Consortium et al. 2007; Buxbaum and Hof 2011; Fernandez et al. 2012; O’Roak et al. 2011; Sakurai et al. 2011) and has demonstrated that ASD and certain other NDDs have a strong hereditary component (Buxbaum and Hof 2011; Sakurai et al. 2011). Linkage studies have identified candidate autism susceptibility genes at multiple loci, most consistently on chromosomes 7q, 15q, and 16p (Autism Genome Project Consortium et al. 2007; Sakurai et al. 2011). Exome sequencing in sporadic cases of autism has detected new mutations (O’Roak et al. 2011), and copy number variant studies have identified several hundred copy number variants putatively linked to autism (Fernandez et al. 2012). The candidate genes most strongly implicated in NDD causation encode for proteins involved in synaptic architecture, neuro-transmitter synthesis (e.g., ©-amino-butyric acid serotonin), oxytocin receptors, and cation trafficking (Sakurai et al. 2011). No single anomaly predominates. Instead, autism appears to be a family of diseases with common pheno-types linked to a series of genetic anomalies, each of which is responsible for no more than 2–3% of cases. The total fraction of ASD attributable to genetic inheri-tance may be about 30–40%.Exploration of the environmental causes of autism and other NDDs has been catalyzed by growing recognition of the exquisite sensitivity of the developing human brain to toxic chemicals (Grandjean and Landrigan 2006). This susceptibility is greatest during unique “windows of vulnerability” that open only in embryonic and fetal life and have no later counter-part (Miodovnik 2011). “Proof of the principle” that early exposures can cause autism comes from studies linking ASD to medications taken in the first trimester of pregnancy—thalidomide, misoprostol, and valproic acid—and to first-trimester rubella infection (Arndt et al. 2005; Daniels 2006).This “proof-of-principle” evidence for environmental causation is supported further by findings from prospective birth cohort epidemio-logical studies, many of them supported by the National Institute of Environmental Health Sciences (NIEHS). These studies enroll women during pregnancy, measure prenatal exposures in real time as they occur, and then follow children longitudinally with periodic direct examinations to assess growth, development, and the presence of disease. Prospective studies are powerful engines for the discovery of etiologic associations between prenatal exposures and NDDs. They have linked autistic behaviors with prenatal exposures to the organophosphate insecticide chlorpyrifos (Eskenazi et al. 2007) and also with prenatal exposures to phthalates (Miodovnik et al. 2011). Additional prospective studies have linked loss of cognition (IQ), dyslexia, and ADHD to lead (Jusko et al. 2008), methyl-mercury (Oken et al. 2008), organophosphate insecticides (London et al. 2012), organo-chlorine insecticides (Eskenazi et al. 2008), polychlorinated biphenyls (Winneke 2011), arsenic (Wasserman et al. 2007), manganese (Khan et al. 2011), polycyclic aromatic hydrocarbons (Perera et al. 2009), bisphenol A (Braun et al. 2011), brominated flame retardants (Herbstman et al. 2010), and perfluorinated compounds (Stein and Savitz 2011).Toxic chemicals likely cause injury to the developing human brain either through direct toxicity or inter-actions with the genome. An expert committee convened by the U.S. National Academy of Sciences (NAS) estimated that 3% of neuro-behavioral disorders are caused directly by toxic environ-mental exposures and that another 25% are caused by inter-actions between environmental factors, defined broadly, and inherited susceptibilities (National Research Council 2000). Epigenetic modification of gene expression by toxic chemicals that results in DNA methyla-tion, histone modification, or changes in activity levels of non-protein-coding RNA (ncRNAs) may be a mechanism of such gene–environment interaction (Grafodatskaya et al. 2010). Epigenetic “marks” have been shown to be able to influence gene expression and alter high-order DNA structure (Anway and Skinner 2006; Waterland and Jirtle 2004).A major unanswered question is whether there are still undiscovered environ-mental causes of autism or other NDDs among the thousands of chemicals currently in wide use in the United States. In the past 50 years, > 80,000 new synthetic chemicals have been developed (Landrigan and Goldman 2011). The U.S. Environmental Protection Agency has identified 3,000 “high production volume” (HPV) chemicals that are in widest use and thus pose greatest potential for human exposure (Goldman 1998). These HPV chemicals are used today in millions of consumer products. Children and pregnant women are exposed extensively to them, and CDC surveys detect quantifiable levels of nearly 200 HPV chemicals in the bodies of virtually all Americans, including pregnant women (Woodruff et al. 2011).The significance of early chemical exposures for children’s health is not yet fully understood. A great concern is that a large number of the chemicals in widest use have not undergone even minimal assessment of potential toxicity, and only about 20% have been screened for potential toxicity during early development (Landrigan and Goldman 2011). Unless studies specifically examine develop-mental consequences of early exposures to untested chemicals, sub-clinical dysfunction caused by these exposures can go unrecognized for years. One example is the “silent epidemic” of childhood lead poisoning: From the 1940s to the 1980s, millions of American children were exposed to excessive levels of lead from paint and gasoline, resulting in reduced average intelligence by 2–5 IQ points (Grosse et al. 2002). The late David Rall, former director of NIEHS, once observed that “If thalidomide had caused a 10-point loss of IQ instead of birth defects of the limbs, it would likely still be on the market” (Weiss 1982).To begin formulation of a systematic strategy for discovery of potentially preventable environmental causes of autism and other NDDs, the Mount Sinai Children’s Environmental Health Center, with the support of the NIEHS and Autism Speaks, convened a workshop on “Exploring the Environmental Causes of Autism and Learning Disabilities.” This workshop produced a series of papers by leading researchers, some of which are published in this issue of Environmental Health Perspectives. It also generated a list of 10 chemi-cals and mixtures widely distributed in the environment that are already suspected of causing develop-mental neuro-toxicity:Lead (Jusko et al. 2008)Methylmercury (Oken et al. 2008)Polychlorinated biphenyls (Winneke 2011)Organophosphate pesticides (Eskenazi et al. 2007; London et al. 2012)Organochlorine pesticides (Eskenazi et al. 2008)Endocrine disruptors (Braun et al. 2011; Miodovnik et al. 2011)Automotive exhaust (Volk et al. 2011)Polycyclic aromatic hydrocarbons (Perera et al. 2009)Brominated flame retardants (Herbstman et al. 2010)Perfluorinated compounds (Stein and Savitz 2011).This list is not exhaustive and will almost certainly expand in the years ahead as new science emerges. It is intended to focus research in environmental causation of NDDs on a short list of chemicals where concentrated study has high potential to generate actionable findings in the near future. Its ultimate purpose is to catalyze new evidence-based programs for prevention of disease in America’s children.The authors declare they have no actual or potential competing -financial interests.ReferencesAnway MD, Skinner MK. 2006. Epigenetic transgenerational actions of endocrine disruptors.Endocrinology 147(6) supplS43-S4916690803. Crossref, Medline, Google ScholarArndt TL, Stodgell CJ, Rodier PM. 2005. The teratology of autism.Int J Dev Neurosci 23:189-19915749245. Crossref, Medline, Google ScholarAutism Genome Project Consortium, Szatmari P, Paterson AD, Zwaigenbaum L, Roberts W, Brian J, et al2007. Mapping autism risk loci using genetic linkage and chromosomal rearrangements.Nat Genet 39:319-32817322880. Crossref, Medline, Google ScholarBraun JM, Kalkbrenner AE, Calafat AM, Yolton K, Ye X, Dietrich KNet al.. 2011. Impact of early-life bisphenol A exposure on behavior and executive function in children.Pediatrics 128(5):873-88222025598. Crossref, Medline, Google ScholarBuxbaum JD, Hof PR. 2011. The emerging neuroscience of autism spectrum disorders. [Editorial]Brain Res 1380:1-221356391. Crossref, Medline, Google ScholarCDC (Centers for Disease Control and Prevention)2005. Mental health in the United States. Prevalence of diagnosis and medication treatment for attention-deficit/hyperactivity disorder–United States, 2003.MMWR Morb Mortal Wkly Rep 54:842-84716138075. Medline, Google ScholarCDC (Centers for Disease Control and Prevention)2012. Prevalence of autism spectrum disorders—autism and developmental disabilities monitoring network, 14 sites, United States, 2008.MMWR Surveill Summ 61(3):1-19. Google ScholarDaniels JL. 2006. Autism and the environment. [Editorial]Environ Health Perspect 114:A39616835036. Link, Google ScholarEskenazi B, Marks AR, Bradman A, Harley K, Barr DB, Johnson Cet al.. 2007. Organophosphate pesticide exposure and neurodevelopment in young Mexican-American children.Environ Health Perspect 115:792-79817520070. Link, Google ScholarEskenazi B, Rosas LG, Marks AR, Bradman A, Harley K, Holland Net al.. 2008. Pesticide toxicity and the developing brain.Basic Clin Pharmacol Toxicol 102(2):228-23618226078. Crossref, Medline, Google ScholarFernandez TV, Sanders SJ, Yurkiewicz IR, Ercan-Sencicek AG, Kim YS, Fishman DOet al.. 2012. Rare copy number variants in tourette syndrome disrupt genes in histaminergic pathways and overlap with autism.Biol Psychiatry 71(5):392-40222169095. Crossref, Medline, Google ScholarGoldman LR. 1998. Chemicals and children’s environment: what we don’t know about risks.Environ Health Perspect 106(suppl 3):875-8809646051. Link, Google ScholarGrafodatskaya D, Chung B, Szatmari P, Weksberg R.. 2010. Autism spectrum disorders and epigenetics.J Am Acad Child Adolesc Psychiatry 49(8):794-80920643313. Crossref, Medline, Google ScholarGrandjean P, Landrigan PJ. 2006. Developmental neurotoxicity of industrial chemicals: a silent pandemic.Lancet 368(9553):2167-217817174709. Crossref, Medline, Google ScholarGrosse SD, Matte TD, Schwartz J, Jackson RJ. 2002. Economic gains resulting from the reduction in children’s exposure to lead in the United States.Environ Health Perspect 110:563-56912055046. Link, Google ScholarHerbstman JB, Sjödin A, Kurzon M, Lederman SA, Jones RS, Rauh Vet al.. 2010. Prenatal exposure to PBDEs and neurodevelopment.Environ Health Perspect 118:712-71920056561. Link, Google ScholarJusko TA, Henderson CR, Lanphear BP, Cory-Slechta DA, Parsons PJ, Canfield RL. 2008. Blood lead concentrations < 10 µg/dL and child intelligence at 6 years of age.Environ Health Perspect 116:243-24818288325. Link, Google ScholarKhan K, Factor-Litvak P, Wasserman GA, Liu X, Ahmed E, Parvez Fet al.. 2011. Manganese exposure from drinking water and children’s classroom behavior in Bangladesh.Environ Health Perspect 119:1501-150621493178. Link, Google ScholarLandrigan PJ, Goldman LR. 2011. Children’s vulnerability to toxic chemicals: a challenge and opportunity to strengthen health and environmental policy.Health Aff 30(5):842-850. Crossref, Google ScholarLondon L, Beseler C, Bouchard MF, Bellinger DC, Colosio C, Grandjean Pet al.. 2012. Neurobehavioral and neurodevelopmental effects of pesticide exposures.Neurotoxicology http://dx.doi.org/10.1016/j.neuro.2012.01.004 [Online 17 January 2012]. Google ScholarMiodovnik A.. 2011. Environmental neurotoxicants and developing brain.Mt Sinai J Med 78(1):58-7721259263. Crossref, Medline, Google ScholarMiodovnik A, Engel SM, Zhu C, Ye X, Soorya LV, Silva MJet al.. 2011. Endocrine disruptors and childhood social impairment.Neurotoxicology 32(2):261-26721182865. Crossref, Medline, Google ScholarNational Research Council. 2000. Scientific Frontiers in Developmental Toxicology and Risk Assessment.Washington, DC:National Academy Press. Google ScholarOken E, Radesky JS, Wright RO, Bellinger DC, Amarasiriwardena CJ, Kleinman KPet al.. 2008. Maternal fish intake during pregnancy, blood mercury levels, and child cognition at age 3 years in a US cohort.Am J Epidemiol 167(10):1171-118118353804. Crossref, Medline, Google ScholarO’Roak BJ, Deriziotis P, Lee C, Vives L, Schwartz JJ, Girirajan Set al.. 2011. Exome sequencing in sporadic autism spectrum disorders identifies severe de novo mutations.Nat Genet 43:585-58921572417. Crossref, Medline, Google ScholarPastor PN, Reuben CA. 2008. Diagnosed attention deficit hyperactivity disorder and learning disability: United States, 2004–2006.Vital Health Stat 10 (237):1-1418998276. Medline, Google ScholarPerera FP, Li Z, Whyatt R, Hoepner L, Wang S, Camann Det al.. 2009. Prenatal airborne polycyclic aromatic hydrocarbon exposure and child IQ at age 5 years.Pediatrics 124(2):e195-e202; doi:10.1542/peds.2008-3506[Online 20 July 2009)19620194. Crossref, Medline, Google ScholarSakurai T, Cai G, Grice DE, Buxbaum JD. 2011. Genomic architecture of autism spectrum disorders.In: Textbook of Autism Spectrum Disorders (Hollander E, Kolevzon A, Coyle JT. eds)Washington, DC:American Psychiatric Publishing281-298. Google ScholarStein CR, Savitz DA. 2011. Serum perfluorinated compound concentration and attention deficit/hyperactivity disorder in children 5–18 years of age.Environ Health Perspect 119:1466-147121665566. Link, Google ScholarTrasande L, Liu Y.. 2011. Reducing the staggering costs of environmental disease in children, estimated at $76.6 billion in 2008.Health Aff 30(5):863-870. Crossref, Google ScholarVolk HE, Hertz-Picciotto I, Delwiche L, Lurmann F, McConnell R. 2011. Residential proximity to freeways and autism in the CHARGE Study.Environ Health Perspect 119:873-87721156395. Link, Google ScholarWasserman GA, Liu X, Parvez F, Ahsan H, Factor-Litvak P, Kline Jet al.. 2007. Water arsenic exposure and intellectual function in 6-year-old children in Araihazar, Bangladesh.Environ Health Perspect 115:285-28917384779. Link, Google ScholarWaterland RA, Jirtle RL. 2004. Early nutrition, epigenetic changes at transposons and imprinted genes, and enhanced susceptibility to adult chronic diseases.Nutrition 20:63-6814698016. Crossref, Medline, Google ScholarWeiss B.. 1982. Food additives and environmental chemicals as sources of childhood behavior disorders.J Am Acad Child Psychiatry 21:144-1527069080. Crossref, Medline, Google ScholarWinneke G.. 2011. Developmental aspects of environmental neurotoxicology: lessons from lead and polychlorinated biphenyls.J Neurol Sci 308(1-2):9-1521679971. Crossref, Medline, Google ScholarWoodruff TJ, Zota AR, Schwartz JM. 2011. Environmental chemicals in pregnant women in the United States: NHANES 2003–2004.Environ Health Perspect 119:878-88521233055. Link, Google ScholarFiguresReferencesRelatedDetailsCited by Chu M, Wu H, Lee C, Chung Y, Chi H, Chen P and Lin H (2022) Generational synaptic functions of GABAA receptor β3 subunit deteriorations in an animal model of social deficit, Journal of Biomedical Science, 10.1186/s12929-022-00835-w, 29:1, Online publication date: 1-Dec-2022. Vejrup K, Brantsæter A, Meltzer H, Mohebbi M, Knutsen H, Alexander J, Haugen M and Jacka F (2022) Prenatal mercury exposure, fish intake and child emotional behavioural regulation in the Norwegian Mother, Father and Child Cohort Study, BMJ Nutrition, Prevention & Health, 10.1136/bmjnph-2021-000412, (e000412) Huang C, Pan S, Chin W, Chen Y, Wu C, Hsu C, Lin P, Chen P and Guo Y (2022) Living proximity to petrochemical industries and the risk of attention-deficit/hyperactivity disorder in children, Environmental Research, 10.1016/j.envres.2022.113128, 212, (113128), Online publication date: 1-Sep-2022. Pagalan L, Oberlander T, Hanley G, Rosella L, Bickford C, Weikum W, Lanphear N, Lanphear B, Brauer M and van den Bosch M (2022) The association between prenatal greenspace exposure and Autism spectrum disorder, and the potentially mediating role of air pollution reduction: A population-based birth cohort study, Environment International, 10.1016/j.envint.2022.107445, 167, (107445), Online publication date: 1-Sep-2022. Angrand L, Masson J, Rubio-Casillas A, Nosten-Bertrand M and Crépeaux G (2022) Inflammation and Autophagy: A Convergent Point between Autism Spectrum Disorder (ASD)-Related Genetic and Environmental Factors: Focus on Aluminum Adjuvants, Toxics, 10.3390/toxics10090518, 10:9, (518) Tywabi-Ngeva Z, Adeniji A and Okaiyeto K (2022) A Global Analysis of Research Outputs on Neurotoxicants from 2011–2020: Adverse Effects on Humans and the Environment, Applied Sciences, 10.3390/app12168275, 12:16, (8275) Karatela S, Ward N, Paterson J and Zeng I (2022) Environmental Influences on the Behavioural and Emotional Outcomes of Children: A Network Analysis, International Journal of Environmental Research and Public Health, 10.3390/ijerph19148479, 19:14, (8479) Li X, Hefti M, Marek R, Hornbuckle K, Wang K and Lehmler H (2022) Assessment of Polychlorinated Biphenyls and Their Hydroxylated Metabolites in Postmortem Human Brain Samples: Age and Brain Region Differences, Environmental Science & Technology, 10.1021/acs.est.2c00581, 56:13, (9515-9526), Online publication date: 5-Jul-2022. Li Y, Zhao Y, Lu Y, Lu X, Hu Y, Li Q, Shuai M and Li R (2022) Autism spectrum disorder-like behavior induced in rat offspring by perinatal exposure to di-(2-ethylhexyl) phthalate, Environmental Science and Pollution Research, 10.1007/s11356-022-19531-1, 29:34, (52083-52097), Online publication date: 1-Jul-2022. Sussman T, Baker B, Wakhloo A, Gillet V, Abdelouahab N, Whittingstall K, Lepage J, St-Cyr L, Boivin A, Gagnon A, Baccarelli A, Takser L and Posner J (2022) The relationship between persistent organic pollutants and Attention Deficit Hyperactivity Disorder phenotypes: Evidence from task-based neural activity in an observational study of a community sample of Canadian mother-child dyads, Environmental Research, 10.1016/j.envres.2021.112593, 206, (112593), Online publication date: 1-Apr-2022. Liu C, Huang L, Huang S, Wei L, Cao D, Zan G, Tan Y, Wang S, Yang M, Tian L, Tang W, He C, Shen C, Luo B, Zhu M, Liang T, Pang B, Li M, Mo Z and Yang X (2022) Association of both prenatal and early childhood multiple metals exposure with neurodevelopment in infant: A prospective cohort study, Environmental Research, 10.1016/j.envres.2021.112450, 205, (112450), Online publication date: 1-Apr-2022. Gadaleta D, Spînu N, Roncaglioni A, Cronin M and Benfenati E (2022) Prediction of the Neurotoxic Potential of Chemicals Based on Modelling of Molecular Initiating Events Upstream of the Adverse Outcome Pathways of (Developmental) Neurotoxicity, International Journal of Molecular Sciences, 10.3390/ijms23063053, 23:6, (3053) Xu H, Jia Y, Sun Z, Su J, Liu Q, Zhou Q and Jiang G (2022) Environmental pollution, a hidden culprit for health issues, Eco-Environment & Health, 10.1016/j.eehl.2022.04.003, 1:1, (31-45), Online publication date: 1-Mar-2022. Torre E and Amarante P (2022) Saúde mental, direitos humanos e justiça ambiental: a ‘quimicalização da vida’ como uma questão de violação de direitos humanos decorrente da intoxicação institucionalizada, Saúde em Debate, 10.1590/0103-11042022e222, 46:spe2, (327-344) Ramírez V, Gálvez-Ontiveros Y, González-Domenech P, Baca M, Rodrigo L and Rivas A (2022) Role of endocrine disrupting chemicals in children's neurodevelopment, Environmental Research, 10.1016/j.envres.2021.111890, 203, (111890), Online publication date: 1-Jan-2022. Keil-Stietz K and Lein P (2022) Gene × environment interactions in autism spectrum disorders , 10.1016/bs.ctdb.2022.11.001, . Dong P, Ye G, Tu X, Luo Y, Cui W, Ma Y, Wei L, Tian X and Wang Q (2021) Roles of ERRα and TGF‑β signaling in stemness enhancement induced by 1 µ M bisphenol A exposure via human neural stem cells , Experimental and Therapeutic Medicine, 10.3892/etm.2021.11087, 23:2 Sethi S, Keil Stietz K, Valenzuela A, Klocke C, Silverman J, Puschner B, Pessah I and Lein P (2021) Developmental Exposure to a Human-Relevant Polychlorinated Biphenyl Mixture Causes Behavioral Phenotypes That Vary by Sex and Genotype in Juvenile Mice Expressing Human Mutations That Modulate Neuronal Calcium, Frontiers in Neuroscience, 10.3389/fnins.2021.766826, 15 Gillera S, Marinello W, Cao K, Horman B, Stapleton H and Patisaul H (2021) Sex-specific Disruption of the Prairie Vole Hypothalamus by Developmental Exposure to a Flame Retardant Mixture, Endocrinology, 10.1210/endocr/bqab100, 162:8, Online publication date: 1-Aug-2021. Modafferi S, Zhong X, Kleensang A, Murata Y, Fagiani F, Pamies D, Hogberg H, Calabrese V, Lachman H, Hartung T and Smirnova L (2021) Gene–Environment Interactions in Developmental Neurotoxicity: a Case Study of Synergy between Chlorpyrifos and CHD8 Knockout in Human BrainSpheres, Environmental Health Perspectives, 129:7, Online publication date: 1-Jul-2021. Baj J, Flieger W, Flieger M, Forma A, Sitarz E, Skórzyńska-Dziduszko K, Grochowski C, Maciejewski R and Karakuła-Juchnowicz H (2021) Autism spectrum disorder: trace elements imbalances and the pathogenesis and severity of autistic symptoms, Neuroscience & Biobehavioral Reviews, 10.1016/j.neubiorev.2021.07.029, Online publication date: 1-Jul-2021. Weiss A, Wilson V and Hopkins W (2021) Early social rearing, the V1A arginine vasopressin receptor genotype, and autistic traits in chimpanzees , Autism Research, 10.1002/aur.2550 Renzetti S, Cagna G, Calza S, Conversano M, Fedrighi C, Forte G, Giorgino A, Guazzetti S, Majorani C, Oppini M, Peli M, Petrucci F, Pino A, Placidi D, Senofonte O, Zoni S, Alimonti A and Lucchini R (2021) The effects of the exposure to neurotoxic elements on Italian schoolchildren behavior, Scientific Reports, 10.1038/s41598-021-88969-z, 11:1 Sendra M, Pereiro P, Figueras A and Novoa B (2021) An integrative toxicogenomic analysis of plastic additives, Journal of Hazardous Materials, 10.1016/j.jhazmat.2020.124975, 409, (124975), Online publication date: 1-May-2021. Win-Shwe T, Kyi-Tha-Thu C, Fujitani Y, Tsukahara S and Hirano S (2021) Perinatal Exposure to Diesel Exhaust-Origin Secondary Organic Aerosol Induces Autism-Like Behavior in Rats, International Journal of Molecular Sciences, 10.3390/ijms22020538, 22:2, (538) Mani S, Jain A, Gulati A, Tyagi S, Pal K, Jaiswal H and Singh M (2021) Oxidative Stress: A Potential Link Between Pesticide Exposure and Early-Life Neurological Disorders Free Radical Biology and Environmental Toxicity, 10.1007/978-3-030-83446-3_10, (209-251), . Robb N, Boyle B, Politis Y, Newbutt N, Kuo H and Sung C (2021) Participatory Technology Design for Autism and Cognitive Disabilities: A Narrative Overview of Issues and Techniques Recent Advances in Technologies for Inclusive Well-Being, 10.1007/978-3-030-59608-8_25, (469-485), . Sharma E, Jacob P, Murthy P, Jain S, Varghese M, Jayarajan D, Kumar K, Benegal V, Vaidya N, Zhang Y, Desrivieres S, Schumann G, Iyengar U, Holla B, Purushottam M, Chakrabarti A, Fernandes G, Heron J, Hickman M, Kartik K, Kalyanram K, Rangaswamy M, Bharath R, Barker G, Orfanos D, Ahuja C, Thennarasu K, Basu D, Subodh B, Kuriyan R, Kurpad S, Kumaran K, Krishnaveni G, Krishna M, Singh R, Singh L and Toledano M (2020) Consortium on Vulnerability to Externalizing Disorders and Addictions (cVEDA): A developmental cohort study protocol, BMC Psychiatry, 10.1186/s12888-019-2373-3, 20:1, Online publication date: 1-Dec-2020. Rosca A, Coronel R, Moreno M, González R, Oniga A, Martín A, López V, González M and Liste I (2020) Impact of environmental neurotoxic: current methods and usefulness of human stem cells, Heliyon, 10.1016/j.heliyon.2020.e05773, 6:12, (e05773), Online publication date: 1-Dec-2020. Kim K, Kwak Y, Han S and Hwang J (2020) Impairment of motor coordination and interneuron migration in perinatal exposure to glufosinate-ammonium, Scientific Reports, 10.1038/s41598-020-76869-7, 10:1 Bauer J, Fruh V, Howe C, White R and Claus Henn B (2020) Associations of Metals and Neurodevelopment: a Review of Recent Evidence on Susceptibility Factors, Current Epidemiology Reports, 10.1007/s40471-020-00249-y Panesar H, Kennedy C, Keil Stietz K and Lein P (2020) Polychlorinated Biphenyls (PCBs): Risk Factors for Autism Spectrum Disorder?, Toxics, 10.3390/toxics8030070, 8:3, (70) Rahbar M, Samms-Vaughan M, Saroukhani S, Lee M, Zhang J, Bressler J, Hessabi M, Shakespeare-Pellington S, Grove M and Loveland K (2020) Interaction of Blood Manganese Concentrations with GSTT1 in Relation to Autism Spectrum Disorder in Jamaican Children, Journal of Autism and Developmental Disorders, 10.1007/s10803-020-04677-z Kamata S, Hashiyama R, Hana-ika H, Ohkubo I, Saito R, Honda A, Anan Y, Akahoshi N, Noguchi K, Kanda Y and Ishii I (2020) Cytotoxicity comparison of 35 developmental neurotoxicants in human induced pluripotent stem cells (iPSC), iPSC-derived neural progenitor cells, and transformed cell lines, Toxicology in Vitro, 10.1016/j.tiv.2020.104999, (104999), Online publication date: 1-Sep-2020. Al-Saleh I, Moncari L, Jomaa A, Elkhatib R, Al-Rouqi R, Eltabache C, Al-Rajudi T, Alnuwaysir H, Nester M and Aldhalaan H (2020) Effects of early and recent mercury and lead exposure on the neurodevelopment of children with elevated mercury and/or developmental delays during lactation: A follow-up study, International Journal of Hygiene and Environmental Health, 10.1016/j.ijheh.2020.113629, 230, (113629), Online publication date: 1-Sep-2020. Carlsson T, Molander F, Taylor M, Jonsson U and Bölte S (2020) Early environmental risk factors for neurodevelopmental disorders – a systematic review of twin and sibling studies, Development and Psychopathology, 10.1017/S0954579420000620, (1-48) Toczylowska B, Zieminska E, Senator P and Lazarewicz J (2020) Hippocampal Metabolite Profiles in Two Rat Models of Autism: NMR-Based Metabolomics Studies, Molecular Neurobiology, 10.1007/s12035-020-01935-0, 57:7, (3089-3105), Online publication date: 1-Jul-2020. Smith M, Yevoo P, Sadahiro M, Readhead B, Kidd B, Dudley J and Morishita H (2020) Systematic Analysis of Environmental Chemicals That Dysregulate Critical Period Plasticity-Related Gene Expression Reveals Common Pathways That Mimic Immune Response to Pathogen, Neural Plasticity, 10.1155/2020/1673897, 2020, (1-10), Online publication date: 5-May-2020. Lenart J, Augustyniak J, Lazarewicz J and Zieminska E (2020) Altered expression of glutamatergic and GABAergic genes in the valproic acid-induced rat model of autism: a screening test, Toxicology, 10.1016/j.tox.2020.152500, (152500), Online publication date: 1-May-2020. Ongono J, Béranger R, Baghdadli A and Mortamais M (2020) Pesticides used in Europe and autism spectrum disorder risk: can novel exposure hypotheses be formulated beyond organophosphates, organochlorines, pyrethroids and carbamates? - A systematic review, Environmental Research, 10.1016/j.envres.2020.109646, (109646), Online publication date: 1-May-2020. Yashomathi (2020) Aided Augmentative and Alternative Communication (AAC) Systems for Individuals With Autism Spectrum Disorders Interdisciplinary Approaches to Altering Neurodevelopmental Disorders, 10.4018/978-1-7998-3069-6.ch006, (87-106) Nadesan M (2020) Autistic ontologies and the open genome Autism 360°, 10.1016/B978-0-12-818466-0.00003-4, (43-62), . Marques L (2020) The Anthropocentric Illusion Capitalism and Environmental Collapse, 10.1007/978-3-030-47527-7_15, (391-429), . Leemans M, Couderq S, Demeneix B and Fini J (2019) Pesticides With Potential Thyroid Hormone-Disrupting Effects: A Review of Recent Data, Frontiers in Endocrinology, 10.3389/fendo.2019.00743, 10 Geier D, Kern J and Geier M (2019) Dow