Weiss Bernard, Bellinger David C
Department of Environmental Medicine, Environmental Health Sciences Center, and Center for Reproductive Epidemiology, University of Rochester School of Medicine and Dentistry, Rochester, New York 14642, USA.
Environ Health Perspect. 2006 Oct;114(10):1479-85. doi: 10.1289/ehp.9101.
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.
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.
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.
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.
生命早期接触神经毒性化学物质的结果取决于化学物质和宿主环境的特性。当我们的问题聚焦于有毒物质时,环境特性往往被视为次要因素,并被指定为协变量或混杂因素。这种方法模糊了早期环境如何建立持久生物底物的现实情况。
在这篇评论中,我们基于对动物数十年的生物心理学研究描述了另一种观点,该观点展示了早期,甚至是产前环境如何在大脑结构、化学和行为方面产生永久性变化。早期环境的各个方面,包括丰富化、剥夺以及母体和新生儿应激,都有助于决定生命后期源自该环境赋予的生物底物的功能反应。然后,它们的影响在生物学上得以嵌入。人类数据,尤其是那些与经济弱势群体相关的数据,也得出了相同的结论。
在这篇评论中,我们认为将这些环境条件视为混杂因素等同于将基因差异定义为混杂因素,而这种策略在诸如基于转基因操作的实验室研究中显然是被摒弃的。其影响范围从隐含地假设早期环境可标准化的实验室实验延伸到基于流行病学调查的风险评估。
早期社会环境植入的生物学特性应被视为从实验室研究转化到人类健康的关键要素,事实上,应将其纳入人类健康研究中。这样做的方法尚未明确界定,给研究人员带来了诸多挑战。