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

描述（由申请人提供）：产后抑郁症（PPD）是一种常见的病态疾病，影响了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（一种在母性和社会行为中起核心作用的神经肽）的减少。拟议的研究将把哺乳作为一种新的生理挑战，以确定低催产素介导PPD和母婴双体发育受损之间的关联程度。本研究的长期目标是识别有PPD风险的母婴，并实施有针对性的干预措施，以解决他们的个人神经内分泌脆弱性，从而改善母亲和孩子的健康。本文的目的是确定催产素和应激反应失调在PPD和双元发育受损的心理生物学中的作用，以母亲敏感性、婴儿情绪调节和不安全依恋为指标。核心假设是PPD与催产素减少和母体HPA轴失调有关，以ACTH和皮质醇之间预期关联的丧失为指标。这些变化降低了产妇的敏感性，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，这些数据显示，在患有产后抑郁症的女性中，催产素减少，下丘脑轴失调。这项工作的基本原理是，随着PPD的潜在机制被确定，干预措施可以针对高危夫妇，减少母亲和婴儿的PPD及其后遗症。在强有力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：使用哺乳作为生理挑战来量化PPD减少催产素，失调应激反应和降低产妇敏感性的程度；2. 使用标准化的母婴互动来确定PPD和母亲敏感性降低对婴儿情绪调节发育的损害程度以及增加不安全依恋风险的程度；3. 确定母体催产素减少和敏感性降低在多大程度上介导PPD、婴儿情绪调节受损和不安全依恋之间的关联。这些目标将通过对200对从怀孕后期到产后12个月的母婴进行纵向研究来实现，其中一半有抑郁和/或焦虑史，一半没有精神病史，并通过诊断访谈得到证实。母子二人组将在母婴生物行为实验室接受评估。该方法具有创新性，因为该项目将把哺乳作为一种生理挑战，量化母体催产素生理学、应激反应、护理、情绪调节和依恋之间的交集，从而揭示母体心理健康和婴儿情感发展。这项研究意义重大，因为它有望确定催产素在PPD和双元发育受损中的作用。最终，这些知识有可能为预防产后抑郁症的新疗法提供信息，并减少母婴的后遗症。

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.