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Toxics 2015, 3(1), 89-129; doi:10.3390/toxics3010089

Multifactorial Origin of Neurodevelopmental Disorders: Approaches to Understanding Complex Etiologies

Unit of Neurotoxicology and Neuroendocrinology, Department of Cell Biology and Neurosciences, Istituto Superiore di Sanità, Viale Regina Elena 299, I-00161 Roma, Italy
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Author to whom correspondence should be addressed.
Academic Editor: David R. Wallace
Received: 29 September 2014 / Revised: 6 March 2015 / Accepted: 18 March 2015 / Published: 23 March 2015
(This article belongs to the Special Issue Developmental Neurotoxicology)
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Abstract

A significant body of evidence supports the multifactorial etiology of neurodevelopmental disorders (NDDs) affecting children. The present review focuses on early exposure to environmental chemicals as a risk factor for neurodevelopment, and presents the major lines of evidence derived from epidemiological studies, underlying key uncertainties and research needs in this field. We introduce the exposome concept that, encompassing the totality of human environmental exposures to multiple risk factors, aims at explaining individual vulnerability and resilience to early chemical exposure. In this framework, we synthetically review the role of variable gene backgrounds, the involvement of epigenetic mechanisms as well as the function played by potential effect modifiers such as socioeconomic status. We describe laboratory rodent studies where the neurodevelopmental effects of environmental chemicals are assessed in the presence of either a “vulnerable” gene background or adverse pregnancy conditions (i.e., maternal stress). Finally, we discuss the need for more descriptive and “lifelike” experimental models of NDDs, to identify candidate biomarkers and pinpoint susceptible groups or life stages to be translated to large prospective studies within the exposome framework. View Full-Text
Keywords: developmental neurotoxicity; autism spectrum disorders; attention deficit hyperactivity disorder; methylmercury; organophosphate pesticides; single nucleotide polymorphisms; maternal stress; exposome; biomarkers; rodents developmental neurotoxicity; autism spectrum disorders; attention deficit hyperactivity disorder; methylmercury; organophosphate pesticides; single nucleotide polymorphisms; maternal stress; exposome; biomarkers; rodents
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

De Felice, A.; Ricceri, L.; Venerosi, A.; Chiarotti, F.; Calamandrei, G. Multifactorial Origin of Neurodevelopmental Disorders: Approaches to Understanding Complex Etiologies. Toxics 2015, 3, 89-129.

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