Intranasal Oxytocin: A Neuropharmacological Intervention for Maternal Neglect?

鼻内催产素：针对母亲忽视的神经药理学干预措施？

• 批准号: 8110650
• 负责人: Lane Strathearn
• 金额: $ 24.88万
• 依托单位: BAYLOR COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-07-15 至 2015-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8110650
• 关键词: Accounting; Adult; Affect; Amygdaloid structure; Animals; Anxiety; Area; Behavior; Behavior Therapy; Behavioral; Biological; Blinded; Brain; Brain region; Child Abuse and Neglect; Child Behavior; Child Development; Classification; Corpus striatum structure; Cross-Over Studies; Cues; Devices; Disease; Dopamine; Dorsal; Effectiveness; Empathy; Enrollment; Epigenetic Process; Equilibrium; Eye; Face; Figs - dietary; Functional Magnetic Resonance Imaging; Future; Hormones; Human; Hypothalamic structure; Image; Individual Differences; Infant; Interpersonal Relations; Intervention; Intervention Studies; Interview; Investigation; Lead; Link; MRI Scans; Maternal Behavior; Measures; Medial; Modeling; Mother-Child Relations; Mothers; Motor output; Neurobiology; Neuropeptides; Neurosecretory Systems; Oxytocin; Pathway interactions; Pattern; Peripheral; Pharmaceutical Preparations; Phase; Placebo Control; Placebos; Play; Population; Prefrontal Cortex; Primary Prevention; Principal Investigator; Procedures; Production; Public Health; Randomized; Randomized Controlled Trials; Recovery; Research; Research Design; Resources; Rewards; Rodent; Rodent Model; Secure; Security; Sensory; Social Behavior; Social Environment; Substantia nigra structure; System; Techniques; Technology; Testing; Time; Trust; United States; United States Dept. of Health and Human Services; United States National Institutes of Health; Ventral Striatum; Ventral Tegmental Area; Videotape; base; caregiving; child neglect; emotional neglect; gaze; indexing; neglect; neuroimaging; offspring; psychosocial; public health relevance; response; reward processing; social

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.

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，对儿童发育产生了一些最严重的长期后果。行为和社会心理干预措施通常是无效的，这可能是由于忽视后代的母亲的固有生物学差异所致。啮齿动物和较新的人类研究表明，神经肽，催产素在促进社会和孕产妇行为方面的重要性。最近证明，首席研究者的成人依恋访谈确定，患有不安全/解雇的成人依恋模式的母亲表明，与自己的婴儿交往时，大脑奖励系统的激活减少和催产素的产生受损。该提案旨在确定鼻内催产素是否会增强母体大脑和对婴儿提示的行为反应，这可能是对孕产妇忽视的神经药理干预措施。一百二十二十个母亲及其年龄的婴儿将被招募参加鼻内催产素的随机，安慰剂控制的跨界研究。将测量功能性MRI大脑对婴儿面孔提示的反应，以及在自由播放互动期间母亲的录像行为反应和修改的静止手术。眼睛跟踪技术还将在扫描仪中使用，以确定催产素在母亲查看婴儿脸部图像时是否会改变眼睛的凝视。假设与安慰剂相比，鼻内催产素将导致大脑中中皮质糖多巴胺奖励区域的激活增加，以响应自己与未知的婴儿面孔提示。在催产素治疗条件下，这种反应也将与增强的婴儿眼凝视有关。接受鼻内催产素的母亲在自由游戏互动期间的总体量度（护理指数）的总体量度上也将获得更高的评分，并将在修改后的静止手术过程中与婴儿表现出更多的情感偶然反应。将在治疗状况，母亲的依恋分类和fMRI会议上，婴儿的脸部影响（快乐与SAD）之间探索相互作用效果。最后，假设大脑奖励激活将与母亲的其他间接疏忽措施有关，包括母亲的敏感性，观看悲伤的婴儿面孔时的眼睛凝视以及在经过改良的仍然是face手术过程中对婴儿提示的孕产妇反应的偶然性。我们预计，这些结果将是未来对母体忽视中鼻内催产素的随机，受控干预研究的基础。 公共卫生相关性：在美国，忽视儿童是一个重要的公共卫生问题，对儿童的成长和行为产生了严重的长期后果。该项目旨在确定天然激素（催产素）是否可以增强母亲对婴儿的粘结反应，如功能性MRI和录像的母亲相互作用所衡量。希望这可能会导致针对母亲依恋疾病的药物治疗。