The existence of a proportional relationship between the number of early-life stress (ELS) events experienced and the impoverishment of child mental health has been hypothesized. However, different types of ELS experiences may be associated with different neuro-psycho-biological impacts, due to differences in the intrinsic nature of the stress. DNA methylation is one of the molecular mechanisms that have been implicated in the “translation” of ELS exposure into neurobiological and behavioral abnormalities during adulthood. Here, we investigated whether different ELS experiences resulted in differential impacts on global DNA methylation levels in the brain and blood samples from mice and humans. ELS exposure in mice resulted in observable changes in adulthood, with exposure to social isolation inducing more dramatic alterations in global DNA methylation levels in several brain structures compared with exposure to a social threatening environment. Moreover, these two types of stress resulted in differential impacts on the epigenetic programming of different brain regions and cellular populations, namely microglia. In a pilot clinical study, blood global DNA methylation levels and exposure to childhood neglect or abuse were investigated in patients presenting with major depressive disorder or substance use disorder. A significant effect of the mental health diagnosis on global methylation levels was observed, but no effect of either childhood abuse or neglect was detected. These findings demonstrate that different types of ELS have differential impacts on epigenetic programming, through DNA methylation in specific brain regions, and that these differential impacts are associated with the different behavioral outcomes observed after ELS experiences.

据推测，经历的早期生活压力（ELS）事件的数量与儿童心理健康状况的恶化之间存在比例关系。但是，由于压力的内在性质不同，不同类型的ELS经历可能与不同的神经心理生物学影响相关。DNA甲基化是成年期ELS暴露“翻译”为神经生物学和行为异常的分子机制之一。在这里，我们调查了不同的ELS经历是否会对小鼠和人类的大脑和血液样本中的总体DNA甲基化水平产生不同的影响。小鼠的ELS暴露导致成年期可观察到的变化，与暴露于具有社会威胁性的环境相比，暴露于社会孤立会导致多个大脑结构的全球DNA甲基化水平发生更大的变化。此外，这两种类型的压力导致对不同大脑区域和细胞群体（即小胶质细胞）的表观遗传程序产生不同的影响。在一项初步的临床研究中，对患有严重抑郁症或药物滥用症的患者的血液总体DNA甲基化水平以及儿童期被忽视或虐待的情况进行了调查。观察到心理健康诊断对总体甲基化水平的显着影响，但未发现儿童期虐待或忽视的影响。这些发现表明，不同类型的ELS对表观遗传编程有不同的影响，