Psychoneuroimmune Contributions to Postpartum Depression

描述（由申请人提供）：产后抑郁症（PPD）发生在高达20%的产后妇女中，其后果可能持续一生。虽然已经确定了几个导致PPD的社会心理变量，但单独考虑这些变量时，PPD的发展仍然存在实质性差异。以下应用侧重于产后期间发生的生理变化，这些变化可能会影响女性从分娩中恢复并陷入抑郁。具体而言，本研究将探讨促炎细胞因子网络对PPD发展的影响，包括直接影响和通过改变其与下丘脑-垂体-肾上腺（HPA）轴激素的双向关系。促炎反应在分娩过程中受到刺激，在产后恢复中起着关键作用。虽然在非怀孕和非产后人群中，过度的促炎反应与抑郁症的发展有关；它在影响产后妇女情绪方面的作用很少得到解决。同样，下丘脑轴在产后也处于变化中；该系统的失调也与非怀孕、非产后人群的抑郁症有关，但是，它在产后妇女抑郁症中的作用尚不清楚。最后，迄今为止没有研究调查炎症细胞因子与HPA轴激素之间的双向相互作用是否会在产后女性中失调，从而增加PPD的风险。在以下应用中，研究人员将对健康妇女进行6次家访，收集数据；一次是在怀孕32-36周，一次是在产后7天和14天，一次是在第1、3和6个月。每次，他们将完成抑郁和压力的调查，并将提供血液样本用于测量促炎和抗炎细胞因子以及HPA轴的激素。为了收集细胞因子和HPA激素的昼夜变化信息，参与者还将在抽血前两天每天收集尿液（细胞因子）和唾液（皮质醇）5次。抑郁症的发展将根据这些变量独立地和相互关联地进行评估。据推测，经历过过度促炎反应的女性会表现出下丘脑轴失调和PPD发病率增加。确定导致产后抑郁症的可改变的生物学风险因素将使保健提供者能够确定处于风险中的妇女，并最终制定有效的战略来预防或减少这种疾病的发展。公共卫生相关性：产后抑郁症是一种潜在的破坏性疾病，在妇女生命中最脆弱和最重要的时期影响她。在这项研究中，我们的目标是更好地了解非抑郁产后妇女的免疫和激素变化，并通过将这些变化与产后抑郁症妇女的变化进行比较，确定这种疾病的生物学基础。

DESCRIPTION (provided by applicant): Postpartum depression (PPD) occurs in up to 20 percent of postpartum women, and carries consequences that may last a lifetime. Although several psychosocial variables contributing to PPD have been identified, substantial variance in the development of PPD remains when considering these variables alone. The following application focuses on physiological changes occurring during the postpartum period that may influence a woman s recovery from childbirth and her descent into depression. Specifically, the proposed study will investigate the impact of the pro-inflammatory cytokine network on the development of PPD, both directly and via alterations in its bidirectional relationship with the hormones of the hypothalamic-pituitary-adrenal (HPA) axis. The pro- inflammatory response is stimulated in women during labor and delivery and plays a key role in postpartum recovery. Although in non-pregnant and non-postpartum populations, an exaggerated pro-inflammatory response has been linked to the development of depression; its role in influencing the mood of postpartum women has been minimally addressed. Likewise, the HPA axis is in flux during the postpartum period; dysregulation of this system also has been linked to depression in non-pregnant, non-postpartum populations, but, again, its role in the depression of postpartum women is unclear. And finally, no studies to date have investigated whether the bidirectional interaction between inflammatory cytokines and HPA axis hormones may become dysregulated in postpartum women, thereby increasing the risk of PPD. In the following application, healthy women will be visited at home by researchers 6 times for data collection; once during weeks 32-36 of pregnancy, and again on postpartum days 7 and 14, and months 1, 3, and 6. Each time, they will complete surveys on depression and stress, and will provide a blood sample for measurement of pro- and anti- inflammatory cytokines and the hormones of the HPA axis. To gather information on diurnal variability in cytokines and HPA hormones, participants also will collect urine (for cytokines) and saliva (for cortisol) 5 times a day for 2-days preceding the blood draw. Development of depression will be evaluated in light of these variables independently and in relation to each other. It is hypothesized that women who experience an exaggerated pro-inflammatory response will demonstrate dysregulation of the HPA axis and an increased incidence of PPD. Identifying modifiable biological risk factors contributing to PPD will enable health care providers to identify women at risk and ultimately, to develop effective strategies to prevent or reduce the development of this disorder. PUBLIC HEALTH RELEVANCE: Postpartum depression is a potentially devastating disorder that affects a woman during one of the most vulnerable and important times of her life. In this study, we aim to better understand the immunological and hormonal changes that occur in non-depressed postpartum women, and, by comparing these changes to those that occur in women with postpartum depression, identify a biological basis for the disorder.