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Review
. 2015 Mar 23;3(1):89-129.
doi: 10.3390/toxics3010089.

Multifactorial Origin of Neurodevelopmental Disorders: Approaches to Understanding Complex Etiologies

Alessia De Felice  1 , Laura Ricceri  2 , Aldina Venerosi  3 , Flavia Chiarotti  4 , Gemma Calamandrei  5
Affiliations
Review

Multifactorial Origin of Neurodevelopmental Disorders: Approaches to Understanding Complex Etiologies

Alessia De Felice et al. Toxics. .

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.

Keywords: attention deficit hyperactivity disorder; autism spectrum disorders; biomarkers; developmental neurotoxicity; exposome; maternal stress; methylmercury; organophosphate pesticides; rodents; single nucleotide polymorphisms.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
The domains of the exposome: different domains (external and internal) are illustrated. Omic signatures of the exposome can be assessed at different developmental stages in the exposed individuals to fully estimate the health impact.
See this image and copyright information in PMC

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