Catale Clarissa, Bussone Silvia, Lo Iacono Luisa, Viscomi Maria Teresa, Palacios Daniela, Troisi Alfonso, Carola Valeria
Department of Psychology, Ph.D. Program in "Behavioral Neuroscience", Sapienza University of Rome, Rome, Italy.
Department of Dynamic and Clinical Psychology, Sapienza University of Rome, Rome, Italy.
Neurobiol Stress. 2020 Sep 2;13:100249. doi: 10.1016/j.ynstr.2020.100249. eCollection 2020 Nov.
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.
有人假设，早年生活应激（ELS）事件的数量与儿童心理健康受损之间存在比例关系。然而，由于应激的内在性质不同，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甲基化是一种分子机制，它与成年期ELS暴露“转化”为神经生物学和行为异常有关。在这里，我们研究了不同的ELS经历是否会对小鼠和人类大脑及血液样本中的整体DNA甲基化水平产生不同影响。小鼠暴露于ELS在成年期会导致可观察到的变化，与暴露于社会威胁环境相比，暴露于社会隔离会在几个脑结构中引起整体DNA甲基化水平更显著的变化。此外，这两种应激对不同脑区和细胞群体（即小胶质细胞）的表观遗传编程产生了不同影响。在一项初步临床研究中，对患有重度抑郁症或物质使用障碍的患者的血液整体DNA甲基化水平以及童年期受忽视或虐待的情况进行了调查。观察到心理健康诊断对整体甲基化水平有显著影响，但未检测到童年期虐待或忽视的影响。这些发现表明，不同类型的ELS通过特定脑区的DNA甲基化对表观遗传编程产生不同影响，并且这些不同影响与ELS经历后观察到的不同行为结果相关。
