Examining an epigenetic biomarker of social perception

社会交往是人际关系形成和发展的重要组成部分。为了促进社会互动，人类已经开发出一套专门的感知技能，允许快速同化社会相关信息。这些技能通常统称为社会感知，在正常发育中，人类大脑形成专门的大脑回路来适应这些技能。社会感知的个体差异具有很强的遗传成分，因此应该由影响这种专门大脑回路的结构和功能的常见遗传变异来介导。然而，当代遗传学技术的重点是DNA序列变异已被限制在解释复杂的社会行为的变异。这个问题的一个潜在解决方案是扩展该方法，以考虑在不改变基因序列的情况下影响基因功能的其他生物过程。这些修饰被称为“表观遗传”，被认为在健康和紊乱的行为中起着关键作用。在国家科学基金会的支持下，弗吉尼亚大学的James Morris和Jessica Connelly博士将人类神经科学与分子遗传学相结合，探索表观遗传过程对支持社会感知的神经回路的作用。该项目的重点是定义个体表观遗传变异沿着催产素受体基因。催产素是一种激素，在哺乳动物大脑中作为一种神经递质，在社会感知中起着关键作用。催产素受体基因的表观遗传修饰影响其功能，因此应该影响由催产素介导的行为。为了验证这一假设，研究人员对受试者的催产素受体基因进行了沿着表观遗传变异性评估，然后在他们执行三项常见任务时对他们的大脑进行扫描，这些任务涉及社会感知的大脑回路。主要分析集中在表观遗传变异性和与社会感知相关的大脑活动之间的关系。二次分析考虑了这种关系如何与复杂的行为，如同理心和压力反应。该项目建立了一个新的范式，以了解遗传变异如何影响社会行为。到目前为止，在考虑基因如何调节大脑活动时，通过现代神经成像技术测量的表观遗传修饰在很大程度上被忽视了。将表观遗传技术应用于社会行为的神经科学研究，将有助于建立人格和个体差异的新模型，并有助于解释由广泛的个体差异定义的精神和发育障碍的脆弱性。该项目为希望在遗传学和人类神经科学方面进行交叉培训的学生提供了一个独特的机会。

Social interaction is a critical component for the formation and development of interpersonal relationships. In order to facilitate social interaction, humans have developed a specialized set of perceptual skills allowing for rapid assimilation of socially relevant information. These skills are often referred to collectively as social perception and in normal development the human brain forms specialized brain circuitry to accommodate these skills. Individual differences in social perception have a strong heritable component and therefore should be mediated by common genetic variation that impacts the structure and function of this specialized brain circuitry. However, contemporary genetic techniques focusing on the DNA sequence variation have been limited in explaining variability in complex social behavior. One potential solution to this problem is to expand the approach to consider other biological processes that impact the function of the gene without changing its sequence. These modifications are referred to as 'epigenetic' and are thought to play a critical role in healthy and disordered behavior. With support from the National Science Foundation, Drs. James Morris and Jessica Connelly of the University of Virginia are combining approaches from human neuroscience with molecular genetics to explore the role of epigenetic processes on neural circuitry supporting social perception. The project focuses on defining individual epigenetic variability along the oxytocin receptor gene. Oxytocin is a hormone that acts as a neurotransmitter in the mammalian brain and plays a critical role in social perception. Epigenetic modification of the oxytocin receptor gene influences its function and therefore should influence behaviors that are mediated by oxytocin. To test this hypothesis, subjects are assessed for epigenetic variability along the oxytocin receptor gene and then have their brains scanned while performing three common tasks that engage brain circuitry underlying social perception. The primary analysis focuses on the relationship between epigenetic variability and brain activity related to social perception. Secondary analyses consider how this relationship is related to complex behaviors such as empathy and stress reactivity. This project establishes a new paradigm to understand how genetic variability can impact social behavior. To date, epigenetic modifications have been largely ignored when considering how genes may modulate brain activity as measured by modern neuroimaging techniques. The application of epigenetic techniques to neuroscientific investigations of social behavior will contribute to new models of personality and individual differences, and help explain vulnerability to psychiatric and developmental disorders that are defined by a wide range of individual differences. The project presents a unique opportunity for students wishing to cross-train in genetics and human neuroscience.