INFLAMMATION FACTORS IN POSTPARTUM DEPRESSION

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 产后抑郁症，通常发生在产后4-6周，是分娩过程中最常见的精神并发症，影响10%-15%的妇女，因此是一个重大的公共卫生问题。分娩后的抑郁症对母亲、孩子和直系亲属都是有害的。如果不治疗，产后抑郁症可能会产生严重的长期后果。在一次产后抑郁发作后，重度抑郁症复发的风险为25%。母亲的抑郁如果得不到治疗，会给孩子带来长期的情绪、行为、认知和人际问题。最严重的产后情感或精神疾病可能会导致母亲自杀或杀害婴儿。由于这些严重的后果，为了更好地了解母亲和孩子的健康和福祉，必须对产后抑郁症的病因进行早期诊断、早期治疗和持续研究。细胞因子是一组异质信使分子，由免疫活性细胞(如淋巴细胞和巨噬细胞)产生，以调节免疫反应。为了治疗目的而给患者服用某些细胞因子，并在健康受试者身上试验性地诱导细胞因子，会导致抑郁症的严重程度增加。对怀孕期间母体免疫系统变化的描述包括免疫系统激活、免疫系统抑制和免疫耐受的证据。与预期的生物学功能一致，月末妇女的细胞因子水平高于未怀孕妇女的细胞因子水平。我们假设产后即刻的炎症可能会在脆弱的女性中引发产后抑郁症状。主要目的：1)评估产后即刻炎症标志物与产后晚期抑郁症状严重程度之间的可能关系。次级目标：2)评价产前、产后早期和产后晚期抑郁评分与炎症标志物的关系。3)探讨产前至产后早期、产前至产后晚期、产后早期至产后晚期抑郁评分变化与炎症标志物变化的关系。50名18岁或以上的产后抑郁症高危孕妇将从马里兰大学妇产科招募。女性必须满足至少一项产后抑郁症的高危标准。受试者将在三个时间点进行研究：怀孕35-38周，分娩后1-5天，以及分娩后5-6周。在每个时间点，将对抑郁评分进行评级，并从外周静脉抽血5茶匙，用于测量受试者血清中下列炎症标志物的水平：C反应蛋白、白介素6和白介素6受体。用于犬尿氨酸和色氨酸测量的额外血清将被冻结，以便在获得额外资金时用于未来的研究。初步分析将是描述性的(连续数据的平均值和标准差，分类数据的比例)。所有连续变量的产前数值变化将在产后1-5天和产后5-6周内计算。计算炎症标志物的变化与汉密尔顿抑郁量表的变化之间的相关性，汉密尔顿抑郁量表是抑郁症严重程度的标准化评定量表，然后进行差异显著性检验。我们的长期目标是描述产后抑郁症的炎症机制，并潜在地确定可能导致产后抑郁症预防性治疗的新的治疗靶点。本申请的目的是为更大规模的NIH拨款申请收集初步数据。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Postpartum depression, most often occurring 4-6 weeks postpartum, is the most common psychiatric complication of childbearing, affecting 10-15% of women and, as such, represents a significant public health concern. Depressive illness following childbirth can be detrimental to the mother, to her children, and to her immediate family. If untreated, postpartum depression can have serious long-term consequences. After one postpartum depressive episode, the risk of recurrence of major depression in is 25%. Untreated depression in the mother leads to long-term emotional, behavioral, cognitive, and interpersonal problems in her children. The most severe cases of postpartum affective or psychotic illness may lead to suicide in the mother or infanticide. Because of these serious consequences, early diagnosis, early treatment and continued research on the etiologies of postpartum depression is imperative in order to better understand the health and well being of both mother and child. Cytokines are a heterogeneous group of messenger molecules that are produced by immunocompetent cells such as lymphocytes and macrophages in order to regulate immune responses. Administration of certain cytokines to patients for therapeutic purposes and induction of cytokines experimentally in healthy subjects results in increased severity of depression. Descriptions of maternal immune system changes during pregnancy include evidence of immune system activation, immune system suppression, and immunological tolerance. Consistent with expected biological functions, cytokine levels in women at end of term are higher than cytokine levels in non-pregnant women. We hypothesize that inflammation in the immediate postpartum period may trigger depressive symptoms postpartum in vulnerable women. Primary aim: 1) To assess a possible relationship between markers of inflammation in the immediate postpartum period, and the severity of depressive symptoms in the late postpartum period. Secondary aims: 2) To assess the relationship between depressive scores and inflammatory markers at each time point: prepartum, early postpartum and late postpartum. 3) To evaluate the relationship between changes in depression scores and changes in inflammatory markers from prepartum to early postpartum, from prepartum to late postpartum, and from early postpartum to late postpartum. Fifty pregnant women 18 years of age or older who are at high risk for postpartum depression will be recruited from the University of Maryland Department of Obstetrics and Gynecology. Women will have to meet at least one of the high-risk criteria for postpartum depression. Subjects will be studied at three time points: at 35-38 weeks gestation, 1-5 days after delivery, and 5-6 weeks after delivery. At each time point there will be a rating of depressive scores and a blood draw of 5 teaspoons from a peripheral vein for measurement of subjects' serum levels for the following inflammatory markers: C-reactive protein, Interleukin-6, and Interleukin-6 Receptor. Additional serum for kynurenine and tryptophan measurements will be frozen for future study when additional funds become available. Initial analyses will be descriptive (means and standard deviations for continuous data and proportions for categorical data). Changes from pre-birth values on all continuous variables will be calculated for 1-5 days postpartum and 5-6 weeks postpartum. Correlations between changes in inflammatory markers and changes on the Hamilton Depression Scale, a standardized rating scale for the severity of depression will be calculated and then tested for significance of difference. Our long-term goal is to describe inflammatory mechanisms of postpartum depression and potentially identify novel therapeutic targets that may lead to prophylactic treatments of postpartum depression. The purpose of this application is to gather preliminary data for a larger NIH grant application.