Department of Psychology, University of Virginia, Charlottesville, VA, USA.
Transl Psychiatry. 2018 Jun 15;8(1):116. doi: 10.1038/s41398-018-0159-x.
Aberrant attentional biases to social stimuli have been implicated in a number of disorders including autism and social anxiety disorder. Oxytocin, a naturally-occurring mammalian hormone and neuromodulator involved in regulating social behavior, has been proposed to impact basic biological systems that facilitate the detection of and orientation to social information. Here, we investigate a role for naturally-occurring variability in the endogenous oxytocinergic system in regulating neural response during attention to social information. Participants performed a selective social attention task while undergoing fMRI, provided a blood sample for epigenetic analysis, and completed self-report measures of social functioning. We find that a functional epigenetic modification to the oxytocin receptor, OXTR methylation, is associated with increased neural response within and decreased functional coupling between regions of the salience and attentional control networks during selective social attention. We also show that subclinical variability in autistic and social anxiety traits moderates this epigenetic regulation of neural response. These data offer a mechanistic explanation to a growing literature associating social behavior and disorder with epigenetic modification to OXTR by suggesting that OXTR methylation reflects a decrease in the extent to which social information automatically captures attention. We highlight the importance that treatment efficacy be considered in relation to individual differences in molecular makeup, and that future studies aimed at uncovering biomarkers of disorder carefully consider measurement at both the biological and phenotypic level.
异常的注意力偏向于社交刺激与许多障碍有关，包括自闭症和社交焦虑障碍。催产素是一种天然存在的哺乳动物激素和神经调节剂，参与调节社会行为，据推测它会影响促进对社交信息的检测和定向的基本生物系统。在这里，我们研究了内源性催产素能系统中自然发生的变异性在调节社交信息注意力过程中的神经反应的作用。参与者在进行 fMRI 时执行选择性社会注意力任务，提供用于表观遗传分析的血液样本，并完成社交功能的自我报告测量。我们发现，催产素受体 OXTR 的一种功能性表观遗传修饰——甲基化，与选择性社会注意力期间，注意力和注意力控制网络区域内的神经反应增加以及功能耦合减少有关。我们还表明，自闭症和社交焦虑特征的亚临床变异性调节了这种神经反应的表观遗传调节。这些数据通过表明 OXTR 甲基化反映了社交信息自动吸引注意力的程度降低，为越来越多的将社会行为和障碍与 OXTR 的表观遗传修饰联系起来的文献提供了一种机制解释。我们强调，在考虑分子构成的个体差异时，必须考虑治疗效果，并且旨在揭示障碍生物标志物的未来研究应仔细考虑在生物学和表型水平上的测量。
