Department of Psychology, University of Denver, Denver, Colorado.
Department of Psychological and Brain Sciences, University of Delaware, Newark, Delaware.
Dev Psychobiol. 2019 Apr;61(3):323-340. doi: 10.1002/dev.21796. Epub 2018 Nov 13.
Advances in epigenetic methodologies have deepened theoretical explanations of mechanisms linking early life stress (ELS) and disease outcomes and suggest promising targets for intervention. To date, however, human studies have not capitalized on the richness of diverse animal models to derive and systematically evaluate specific and testable hypotheses. To promote cross-species dialog and scientific advance, here we provide a classification scheme to systematically evaluate the match between characteristics of human and animal studies of ELS and DNA methylation. Three preclinical models were selected that are highly cited, and that differ in the nature and severity of the ELS manipulation as well as in the affected epigenetic loci (the licking and grooming, maternal separation, and caregiver maltreatment models). We evaluated the degree to which human studies matched these preclinical models with respect to the timing of ELS and of DNA methylation assessment, as well as the type of ELS, whether sex differences were explicitly examined, the tissue sampled, and the targeted loci. Results revealed <50% match (range of 8-83%) between preclinical models and human work on these variables. Immediate and longer-term suggestions to improve translational specificity are offered, with the goal of accelerating scientific advance.
表观遗传方法的进展深化了对早期生活应激 (ELS) 与疾病结果之间联系的机制的理论解释，并为干预提供了有前途的靶点。然而，迄今为止，人类研究尚未充分利用各种动物模型的丰富性来得出和系统评估具体和可检验的假设。为了促进跨物种对话和科学进步，我们在此提供了一种分类方案，以系统地评估 ELS 和 DNA 甲基化的人类和动物研究特征之间的匹配程度。选择了三个被高度引用的临床前模型，它们在 ELS 处理的性质和严重程度以及受影响的表观遗传位点（舔舐和梳理、母婴分离和照顾者虐待模型）方面存在差异。我们评估了人类研究在 ELS 和 DNA 甲基化评估的时间、ELS 的类型、是否明确检查性别差异、取样组织以及靶向基因座方面与这些临床前模型的匹配程度。结果表明，在这些变量方面，临床前模型与人类工作的匹配程度<50%（范围为 8-83%）。我们提供了即时和长期的建议，以提高转化的特异性，从而加速科学进步。
