Division of Medical Pharmacology, Leiden/Amsterdam Center for Drug Research, Gorlaeus Laboratories, Leiden University, P.O. Box 9502, 2300 RA, Leiden, The Netherlands.
Psychopharmacology (Berl). 2011 Mar;214(1):141-54. doi: 10.1007/s00213-010-2118-y. Epub 2010 Dec 18.
Human epidemiology and animal studies have convincingly shown the long-lasting impact of early life experiences on the development of individual differences in stress responsiveness in later life. The interplay between genes and environment underlies this phenomenon.
We provide an overview of studies investigating the impact of early life experiences on the development of individual differences in neuroendocrine stress responsiveness in adulthood and address (1) impact of environment on later stress phenotypes, (2) role of genetic factors in modulating the outcome of environment, and (3) role of nonshared environmental experience in the outcome of gene × environment interplays. We present original findings where we investigated the influence of nonshared experiences in terms of individual differences in maternal care received, on the development of stress phenotype in later life in rats.
Environmental influences in early life exert powerful effects on later stress phenotypes, but they do not always lead to expression of diseases. Heterogeneity in response is explained by the role of particular genetic factors in modulating the influence of environment. Nonshared experiences are important in the outcome of gene × environment interplays in humans. We show that nonshared experiences acquired through within-litter variation in maternal care in rats predict the stress phenotype of the offspring.
The outcome of early experience is not deterministic and depends on several environmental and genetic factors interacting in an intricate manner to support stress adaptation. The degree of "match" and "mismatch" between early and later life environments predicts resilience and vulnerability to stress-related diseases, respectively.
人类流行病学和动物研究有力地证明了早期生活经历对个体在以后生活中对应激反应的差异发展的持久影响。基因与环境的相互作用是这一现象的基础。
我们概述了研究早期生活经历对成年后神经内分泌应激反应个体差异发展影响的研究，并探讨了（1）环境对后期应激表型的影响，（2）遗传因素在调节环境结果中的作用，以及（3）非共享环境经验在基因-环境相互作用结果中的作用。我们提出了一些原创性发现，研究了在大鼠中，通过接受不同的母婴护理的个体差异来评估非共享经验对后期应激表型发展的影响。
早期生活中的环境影响对后期的应激表型有强大的作用，但并不总是导致疾病的表现。遗传因素在调节环境影响方面的作用解释了反应的异质性。非共享经验在人类中基因-环境相互作用的结果中很重要。我们表明，大鼠通过母婴护理的个体差异获得的非共享经验可以预测后代的应激表型。
早期经验的结果不是确定性的，取决于几种环境和遗传因素以复杂的方式相互作用，以支持应激适应。早期和后期生活环境之间的“匹配”和“不匹配”程度分别预测了对与应激相关的疾病的韧性和脆弱性。
