Mood, mother and infant: The psychobiology of impaired dyadic development

描述(申请人提供)：产后抑郁症(PPD)是一种常见的病态疾病，影响10%-15%的母亲。最近的研究表明，在这种疾病的病理生理学中，催产素减少，这是一种在母性和社会行为中发挥核心作用的神经肽。这项拟议的研究将把哺乳作为一种新的生理学挑战，以确定低催产素在多大程度上调节产后抑郁和母婴二分体发育受损之间的联系。这项研究的长期目标是确定有产后抑郁风险的母婴并实施有针对性的干预措施，以解决他们个人的神经内分泌脆弱性，从而改善母婴的健康。这里的目的是确定催产素和失调的应激反应在产后抑郁和二元发育受损的心理生物学中的作用，以母亲的敏感性、婴儿的情绪调节和不安全的依恋为指标。中心假设是PPD与催产素减少和母体HPA轴失调有关，以失去ACTH和皮质醇之间的预期关联为指标。这些变化降低了母亲的敏感度，损害了二元发育，增加了不安全依恋的风险。这一假设是基于已发表的文献和初步数据提出的，这些数据表明，在有产后抑郁症状的女性中，催产素减少和HPA轴调节失调。这项工作的基本原理是，随着产后抑郁的潜在机制被确定，可以开发针对高危二联体的干预措施，并减少产后抑郁及其对母婴的后遗症。在强大的初步数据的指导下，中心假设将通过追求三个具体目标来检验：1.将哺乳作为一种生理挑战，以量化PPD降低催产素、调节应激反应和降低母亲敏感性的程度；2.使用标准化的母婴互动来确定PPD和母亲敏感性降低在多大程度上损害婴儿情绪调节的发展并增加不安全依恋的风险；3.确定母亲催产素减少和敏感性降低在多大程度上中介了PPD、婴儿情绪调节受损和不安全依恋之间的联系。这些目标将通过对200对母婴进行纵向研究来实现，这些母婴跨越怀孕后期到产后12个月，其中一半有抑郁和/或焦虑的病史，另一半没有精神病史，经诊断性访谈证实。在访问母婴生物行为实验室期间，将对母婴二元组进行评估。这个方法是创新的，因为这个项目将把哺乳作为一个生理学挑战，量化母亲催产素生理学、应激反应、照顾、情绪调节和依恋之间的交集，从而揭示母亲的心理健康和婴儿的情感发展。这项拟议的研究意义重大，因为它有望确定催产素在产后抑郁和发育障碍中的作用。最终，这些知识有可能为预防产后抑郁并减少母婴后遗症的新疗法提供信息。

DESCRIPTION (provided by applicant): Postpartum depression (PPD) is a common, morbid condition that affects 10-15% of mothers. Recent work implicates reductions in oxytocin, a neuropeptide that plays a central role in mothering and social behavior, in the pathophysiology of this disorder. The proposed study will use lactation as a novel physiologic challenge to determine the extent to which low oxytocin mediates associations between PPD and impaired development of the mother-infant dyad. The long-term goal of this research is to identify mother-infant dyads at risk of PPD and implement targeted interventions to address their personal neuroendocrine vulnerabilities, thereby improving the health of mother and child. The objective here is to define the role of oxytocin and dysregulated stress reactivity in the psychobiology of PPD and impaired dyadic development, indexed by maternal sensitivity, infant emotional regulation, and insecure attachment. The central hypothesis is that PPD is associated with reduced oxytocin and maternal HPA axis dysregulation, indexed by loss of expected associations between ACTH and cortisol. These changes reduce maternal sensitivity, impairing dyadic development and increasing risk for insecure attachment. This hypothesis has been formulated based on published literature and preliminary data showing diminished oxytocin and dysregulation of the HPA axis among women with PPD symptoms. The rationale for this work is that as the underlying mechanisms of PPD are identified, interventions can be developed to target at-risk dyads and diminish PPD and its sequelae for mother and infant. Guided by strong preliminary data, the central hypothesis will be tested by pursuing three specific aims: 1. Use lactation as a physiologic challenge to quantify the extent to which PPD reduces oxytocin, dysregulates stress reactivity, and diminishes maternal sensitivity; 2. Use standardized mother-infant interactions to determine the extent to which PPD and reduced maternal sensitivity impair development of infant emotional regulation and increase risk for insecure attachment; 3. Determine the extent to which diminished maternal oxytocin and reduced sensitivity mediate associations between PPD, impaired infant emotional regulation, and insecure attachment. These aims will be achieved through a longitudinal study of 200 mother-infant dyads spanning late pregnancy through 12 months postpartum, half with a history of depression and/or anxiety and half with no psychiatric history, confirmed by diagnostic interview. Mother-infant dyads will be assessed during visits to the Mother-Infant Biobehavioral Lab. The approach is innovative, because this project will use lactation as a physiologic challenge to quantify intersections among maternal oxytocin physiology, stress reactivity, care giving, emotional regulation, and attachment, thereby shedding light on both maternal mental health and infant emotional development. The proposed research is significant, because it is expected to define the role of oxytocin in PPD and impaired dyadic development. Ultimately, such knowledge has the potential to inform novel therapies to prevent PPD and reduce its sequelae for mother and child.