Human Microbiome and Perinatal Depression

项目摘要/摘要 抑郁症是怀孕期间最常见的并发症，影响10%-20%的女性。高达75%的女性 患有围产期抑郁症的人得不到心理健康护理。在低收入非洲裔美国人和西班牙裔美国人中 在妇女中，围产期抑郁症(PND)的患病率特别高，治疗率较低。 认知行为疗法(CBT)是一种有效的治疗方法，但存在时间承诺等实际障碍， 保险覆盖范围、交通以及耻辱限制了特别是少数族裔妇女接受CBT。 同样，对抗抑郁药物治疗对母婴结局的不利影响的担忧也限制了 对药物治疗的吸收。开发安全的抑郁症治疗药物的新途径 专注于大脑-肠道轴，并得到益生菌可以改善情绪的初步证明的支持 症状。我们的长期目标是帮助发现与PND相关的潜在微生物， 并可能成为诊断和治疗这种疾病的新生物标记物，特别是在少数族裔妇女中。 作为第一步，我们提出了一个多PI可行性研究，涉及实施和优化 招募参与者和收集粪便样本的程序，以及对 重度抑郁障碍孕妇与非重度抑郁症孕妇肠道微生物区系的纵向差异 (MDD)。为了实现这些目标，我们将利用现有的研究基础设施进行前瞻性、 嵌套式病例对照研究。我们将前瞻性地收集抑郁症的诊断和肠道微生物组样本 300名妇女在怀孕期间和分娩后的四个时间点总共产生了58名妇女，29例MDD 29例非MDD对照。这两组人将在关键协变量上进行匹配(例如，年龄、种族、社会- 经济状况、孕龄、健康)。在他们预定的常规护理，产前预约，同意 参与者将完成心理健康、人口统计学、微生物组相关以及饮食和身体习惯 并在预约时或在家中提供粪便样本。为了实现我们的目标 第一个目标-确定一个更大的类似设计研究的可行性-我们将估计 潜在参与者，评估和未评估资格(及原因)的人数，排除的人数 以及被排除的原因，失去的后续行动的数量，以及可供分析的数据 来访。为了实现我们的第二个目标--确定怀孕期间肠道微生物群是否动态不同 患有和不患有MDD的女性-我们将采用一套系统级别的方法，包括多变量 统计技术、网络建模和机器学习技术。这款R03将允许我们优化 我们未来收集粪便样本和心理健康数据的研究过程正在准备中 用于更大的嵌套病例对照研究，并最终用于PND的益生菌疗法的临床试验。

Project Summary/Abstract Depression is the most common complication of pregnancy and affects 10-20% of women. Up to 75% of women with perinatal depression do not receive mental health care. In lower income African American and Hispanic women, the prevalence of perinatal depression (PND) is particularly high and the treatment rates are lower. Cognitive behavioral therapy (CBT) is an effective treatment but practical barriers such as time commitment, insurance coverage, and transportation, as well as stigma, limit uptake of CBT particularly for minority women. Similarly, concern about the adverse effects of antidepressant treatment on maternal and infant outcomes limits uptake of pharmacological treatments. A novel avenue for the development of safe therapeutics for depression focuses on the brain-gut axis and is supported by initial demonstrations that probiotics can improve mood symptoms. Our long-term goal is to assist in the discovery of potential microbes that are correlated with PND, and could be novel biomarkers for the diagnosis and treatment of this disorder, particularly in minority women. As a first step, we propose a multi-PI feasibility study involving the implementation and optimization of processes for participant recruitment and stool sample collection, as well as the initial assessments of longitudinal differences in gut microbiota between pregnant women with and without major depressive disorder (MDD). To meet these goals, we will leverage an established research infrastructure to conduct a prospective, nested case-control study. We will prospectively collect depression diagnoses and gut microbiome samples on 300 women at four points during pregnancy and after delivery to yield a total of 58 women, 29 cases with MDD and 29 controls without MDD. The two groups will be matched on key covariates (e.g., age, race, socio- economic status, gestational age, health). At their scheduled usual care, prenatal appointment, consented participants will complete mental health, demographics, microbiome-related, and dietary and physical habits questionnaires and provide a fecal sample either at that time of their appointment or at home. To achieve our first aim - to determine the feasibility of a larger similarly designed study - we will estimate the total number of potential participants, the number assessed and not assessed for eligibility (and reasons), the number excluded and reasons for exclusion, the number lost to follow-up, and the data available for analysis at each of the 4 visits. To achieve our second aim - to determine whether the gut microbiome dynamically differs in pregnant women with and without MDD - we will employ a suite of systems level approaches, including multivariate statistical techniques, network modeling and machine learning techniques. This R03 will allow us to optimize our research processes for the prospective collection of stool samples and mental health data in preparation for larger nested case-control studies, and ultimately clinical trials of probiotic therapies for PND.