BACKGROUND: The outcomes of exposure to neurotoxic chemicals early in life depend on the properties of both the chemical and the host's environment. When our questions focus on the toxicant, the environmental properties tend to be regarded as marginal and designated as covariates or confounders. Such approaches blur the reality of how the early environment establishes enduring biologic substrates.
OBJECTIVES: In this commentary, we describe another perspective, based on decades of biopsychological research on animals, that shows how the early, even prenatal, environment creates permanent changes in brain structure and chemistry and behavior. Aspects of the early environment--encompassing enrichment, deprivation, and maternal and neonatal stress--all help determine the functional responses later in life that derive from the biologic substrate imparted by that environment. Their effects then become biologically embedded. Human data, particularly those connected to economically disadvantaged populations, yield equivalent conclusions.
DISCUSSION: In this commentary, we argue that treating such environmental conditions as confounders is equivalent to defining genetic differences as confounders, a tactic that laboratory research, such as that based on transgenic manipulations, clearly rejects. The implications extend from laboratory experiments that, implicitly, assume that the early environment can be standardized to risk assessments based on epidemiologic investigations.
CONCLUSIONS: The biologic properties implanted by the early social environment should be regarded as crucial elements of the translation from laboratory research to human health and, in fact, should be incorporated into human health research. The methods for doing so are not clearly defined and present many challenges to investigators.
KEY WORDS: covariates, effect modification, environment deprivation, environmental enrichment, risk assessment, stress. Environ Health Perspect 114:1479-1485 (2006). doi:10.1289/ehp.9101 available via http://dx.doi.org/ [Online 10 May 2006]
In this commentary, we argue that the outcomes of exposure to neurotoxic chemicals early in life are shaped by the nature of a child's social environment, including that prevailing before birth. Our guiding thesis is that toxicity is not simply an inherent property of the toxicant but derives from an assortment of jointly acting variables bound implacably into the individual. Neurotoxicology accepts genetic predispositions as intrinsic influences, but aspects of the broader environment, especially its social characteristics, tend to be either regarded, at best, as a marginal influence or dismissed as merely a nuisance, contributing a source of confounding bias. We contend that a true evaluation of toxic potential and its neurobehavioral consequences is inseparable from the ecologic setting in which they act and which creates unique, enduring individual vulnerabilities that warrant the same status as genetic predispositions and are imprinted as forcefully. Although aspects of this perspective are well accepted among neurotoxicologists, it has not yet found wide application in study design and analysis. Therefore, we also suggest factors, which are primarily methodologic, that appear to be important impediments.
The Customary Approach to Human Studies
Environmental chemicals comprise only one of many exogenous factors that can influence child development. Recognizing this principle, investigators attempting to determine whether and how a particular agent induces developmental neurotoxicity strive to separate its unique contribution from those of the larger, particularly social environment. Such investigations tend to strip away those contributions (covariates, confounders) statistically through techniques such as multiple regression. The major goal of such analyses is to avoid misattributing to the …