University of California Los Angeles, United States.
Northwestern University, United States.
Neurosci Biobehav Rev. 2017 Sep;80:166-184. doi: 10.1016/j.neubiorev.2017.05.020. Epub 2017 May 31.
Childhood adversity has been repeatedly and robustly linked to physical and mental illness across the lifespan. Yet, the biological pathways through which this occurs remain unclear. Functioning of the inflammatory arm of the immune system and the hypothalamic-pituitary-adrenal (HPA)-axis are both hypothesized pathways through which childhood adversity leads to disease. This review provides a novel developmental framework for examining the role of adversity type and timing in inflammatory and HPA-axis functioning. In particular, we identify elements of childhood adversity that are salient to the developing organism: physical threat, disrupted caregiving, and unpredictable environmental conditions. We propose that existing, well-characterized animal models may be useful in differentiating the effects of these adversity elements and review both the animal and human literature that supports these ideas. To support these hypotheses, we also provide a detailed description of the development and structure of both the HPA-axis and the inflammatory arm of the immune system, as well as recent methodological advances in their measurement. Recommendations for future basic, developmental, translational, and clinical research are discussed.
儿童时期的逆境经历与整个生命周期中的身心健康问题密切相关。然而，目前尚不清楚其中的生物学机制。人们普遍认为，免疫系统的炎症反应和下丘脑-垂体-肾上腺（HPA）轴的功能失调可能是导致儿童时期逆境与疾病相关的两种生物学途径。本综述为研究逆境类型和发生时间在炎症反应和 HPA 轴功能中的作用提供了一个新的发展框架。具体而言，我们确定了与发育中的生物体相关的一些儿童逆境因素：身体威胁、养育中断和不可预测的环境条件。我们提出，现有的、特征明确的动物模型可能有助于区分这些逆境因素的影响，并回顾了支持这些观点的动物和人类文献。为了支持这些假设，我们还详细描述了 HPA 轴和免疫系统炎症反应的发展和结构，以及它们测量方法的最新进展。讨论了未来基础、发展、转化和临床研究的建议。
