University of Virginia, Department of Psychology.
Soc Cogn Affect Neurosci. 2018 Nov 8;13(11):1155-1162. doi: 10.1093/scan/nsy086.
Oxytocin has anxiolytic properties whose mechanisms of action are still being identified. DNA methylation in the promoter region of the oxytocin receptor gene (OXTR), an epigenetic modification that putatively reflects a downtuning of the oxytocin system, has previously been implicated in the regulation of fear-related responses through the amygdala. In this study, we attempted to characterize the relationship between methylation of OXTR and anxiogenesis using two distinct endophenotypes: autonomic nervous system activity and subcortical brain structure. In 79 participants, we found that increased OXTR methylation is associated with attenuated resting parasympathetic tone, measured using high-frequency heart rate variability. Further, we found that this relationship is mediated by brain morphology, such that OXTR methylation is associated with increased gray matter of the central amygdala which is, in turn, associated with decreased parasympathetic tone. These results further our understanding of epigenetic regulation of the human oxytocin system and its role in anxiogenesis.
催产素具有抗焦虑特性，其作用机制仍在确定中。催产素受体基因（OXTR）启动子区域的 DNA 甲基化是一种表观遗传修饰，据称可以反映催产素系统的下调，先前与杏仁核中的恐惧相关反应的调节有关。在这项研究中，我们试图通过两种不同的内表型来描述 OXTR 甲基化与焦虑发生之间的关系：自主神经系统活动和皮质下脑结构。在 79 名参与者中，我们发现增加的 OXTR 甲基化与静息时副交感神经张力减弱有关，这是通过高频心率变异性测量得到的。此外，我们发现这种关系受大脑形态的介导，即 OXTR 甲基化与中央杏仁核的灰质增加有关，而灰质的增加又与副交感神经张力的降低有关。这些结果进一步了解了人类催产素系统的表观遗传调控及其在焦虑发生中的作用。
