Intranasal Oxytocin: A Neuropharmacological Intervention for Maternal Neglect?

描述（由申请人提供）：虐待儿童是最常见但研究最少的虐待儿童形式，对儿童发育有一些最严重的长期后果。行为和心理社会干预往往是无效的，可能是由于先天的生物差异，母亲谁忽视他们的后代。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。主要研究者最近证明，从成人依恋访谈中确定的成人依恋不安全/不信任模式的母亲在与自己的婴儿接触时表现出大脑奖励系统激活减少和催产素产生受损。这项建议的目的是确定是否鼻内催产素增强产妇的大脑和行为反应的婴儿线索，作为一种可能的神经药理学干预产妇忽视。将招募120名第一次分娩的母亲及其足月婴儿参加鼻内催产素的随机、安慰剂对照交叉研究。将测量功能性MRI大脑对婴儿面部线索的反应，以及母亲在自由玩耍互动和修改后的静止面部程序中的行为反应录像。眼动追踪技术也将用于扫描仪，以确定催产素是否会改变母亲观看婴儿面部图像时的眼睛注视模式。据推测，鼻内催产素，与安慰剂相比，将导致增加激活大脑中皮质边缘多巴胺奖励区，响应自己与未知的婴儿面部线索。这种反应也将与催产素治疗条件下增强的婴儿眼睛注视相关。接受鼻内催产素的母亲在自由玩耍互动期间的母体敏感性的总体测量（CARE指数）上也会得分更高，并且在改良的静止面部程序期间会与婴儿表现出更多的情绪反应。将探讨治疗条件，母亲的依恋分类，并在功能磁共振成像会议，婴儿的脸影响（快乐与悲伤）之间的相互作用。最后，据推测，大脑奖励激活将与母亲的情绪忽视的其他间接措施，包括产妇的敏感性，眼睛注视时，观看悲伤的婴儿的脸，并在修改后的静止的脸程序的母亲对婴儿线索的应急反应。我们预计，这些结果将是未来的随机对照干预研究的基础上，鼻内催产素在产妇忽视。 公共卫生相关性：儿童忽视是美国一个重大的公共卫生问题，对儿童的发展和行为产生严重的长期后果。该项目旨在确定一种天然激素，催产素，是否可以增强母亲对婴儿的结合反应，通过功能性磁共振成像和母婴互动录像来测量。希望这可能会导致一种药物治疗母婴依恋障碍。

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.