Intranasal Oxytocin: A Neuropharmacological Intervention for Maternal Neglect?

描述（由申请人提供）：忽视是最常见但研究最少的儿童虐待形式，对儿童发展有一些最严重的长期后果。行为和社会心理干预往往是无效的，可能是由于忽视子女的母亲的内在生物学差异。啮齿动物和最近的人类研究已经证明了神经肽催产素在促进社会和母性行为方面的重要性。首席研究员最近证明，根据成人依恋访谈，具有不安全/拒绝成人依恋模式的母亲在与自己的婴儿交往时，表现出大脑奖励系统激活减少，催产素产生受损。本研究旨在确定鼻内催产素是否能增强母亲大脑和行为对婴儿线索的反应，作为一种可能的神经药理学干预产妇忽视。121名首次分娩的母亲和她们的足月婴儿将被纳入一项随机、安慰剂对照的鼻内催产素交叉研究。对婴儿面部线索的功能性核磁共振大脑反应将被测量，以及母亲在自由玩耍互动和改进的静止面部程序中的行为反应的录像。眼动追踪技术也将用于扫描仪，以确定当母亲看到婴儿面部图像时，催产素是否会改变眼睛的注视模式。据推测，与安慰剂相比，鼻内催产素会导致大脑中皮质边缘多巴胺奖励区域的激活增加，以响应自己或未知的婴儿面部线索。这种反应也将与催产素治疗条件下婴儿眼睛注视的增强有关。接受鼻内催产素治疗的母亲在自由游戏互动（关爱指数）中对母亲敏感性的总体衡量也会得到更高的分数，并且在改进的静止面部程序中对婴儿表现出更多的情感上的偶然反应。将探讨治疗条件、母亲依恋分类和婴儿面部影响（快乐与悲伤）之间的交互效应。最后，假设大脑奖励激活将与母亲情绪忽视的其他间接测量相关联，包括母亲的敏感性，当看到悲伤的婴儿脸时的眼睛注视，以及在修改的静止脸程序中母亲对婴儿线索的反应的偶然性。我们预计这些结果将成为未来鼻内催产素在产妇忽视中的随机对照干预研究的基础。

DESCRIPTION (provided by applicant): Neglect is the most common but least studied form of child maltreatment, with some of the most serious long- term consequences for child development. Behavioral and psychosocial interventions are frequently ineffective, possibly due to inherent biological differences in mothers who neglect their offspring. Rodent and more recent human research has demonstrated the importance of the neuropeptide, oxytocin, in facilitating social and maternal behaviors. The Principal Investigator was recently demonstrated that mothers with an insecure/dismissing pattern of adult attachment, as determined from the Adult Attachment Interview, show reduced brain reward system activation and impaired oxytocin production when engaging with their own infant. This proposal aims to determine whether intranasal oxytocin enhances maternal brain and behavioral responses to infant cues, as a possible neuropharmacological intervention for maternal neglect. One hundred and twenty first time mothers and their term infants will be enrolled to participate in a randomized, placebo- controlled crossover study of intranasal oxytocin. Functional MRI brain responses to infant face cues will be measured, as well as videotaped behavioral responses of mothers during a free-play interaction and a modified still-face procedure. Eye tracking technology will also be utilized in the scanner to determine whether oxytocin alters patterns of eye gaze when mothers view infant face images. It is hypothesized that intranasal oxytocin, compared with placebo, will result in increased activation of mesocorticolimbic dopamine reward regions in the brain, in response to own vs. unknown infant face cues. This response will also be associated with enhanced infant eye gaze in the oxytocin treatment condition. Mothers who receive intranasal oxytocin will also score higher on an overall measure of maternal sensitivity during a free play interaction (the CARE-Index), and will display more emotionally contingent responses with their infant during a modified still-face procedure. Interaction effects will be explored between treatment condition, mother's attachment classification and, in fMRI sessions, infant face affect (happy vs. sad). Finally, it is hypothesized that brain reward activation will be associated with other indirect measures of emotional neglect in mothers, including maternal sensitivity, eye gaze when viewing sad infant faces, and the contingency of maternal responses to infant cues during the modified still-face procedure. We anticipate that these results will be the basis for future randomized, controlled intervention studies of intranasal oxytocin in maternal neglect. PUBLIC HEALTH RELEVANCE: Child neglect is a significant public health issue in the United States, with serious long- term consequences for child development and behavior. This project aims to determine whether a natural hormone, oxytocin, may enhance a mother's bonding response to her baby, as measured by functional MRI and videotaped mother-infant interactions. The hope is that this may lead to a drug treatment for disorders of mother-infant attachment.