Cerebrospinal fluid (CSF) and peripheral markers of the neuropsychiatric sequelae of COVID-19: The Generation C-SF pregnancy study

摘要 胎盘是怀孕期间不可或缺的器官，是宫内环境的调节器，包括 母体神经内分泌改变。先前的努力已经开始阐明HPA轴之间的联系 胎盘中的基因表达和母亲的心理健康，暗示基因表达失调 对孕妇的身心健康有潜在的影响。 充分审问这一联系势在必行，迫切需要扩大我们对 胎盘基因表达所起的作用。这在冠状病毒病的背景下尤其重要 2019年(新冠肺炎)大流行，因为感染及其引发的炎症反应有可能 对产妇心理健康的负面影响。母公司研究(一代CSF)目前正在使用大型 正在进行的妊娠队列调查SARS-CoV-2感染和随后炎症的影响 配对血液和脑脊液标本对产妇心理健康和认知的影响 以及怀孕期间和怀孕后的精神和认知评估。本副刊旨在进一步阐述 这项研究通过澄清胎盘作为神经内分泌机会的调节器可能扮演的角色 在这段关系中扮演角色。通过利用已经收集的胎盘样本和现有的RNAseq数据来 研究胎盘中的免疫和炎症基因，这些基因与 产妇的心理健康，这一补充提供了关于什么可能是驱动因素的重要补充信息 被提议的在怀孕期间感染后发生的整个系统的负面变化。我们假设 孕期感染SARS-CoV-2将与免疫和免疫球蛋白表达呈正相关 胎盘和母体血液中的炎症标志物，这种上调将成为 出生时和产后6周的EPDS评分增加。在目标1中，我们将研究两者之间的关联 SARS-CoV-2感染与497个免疫和炎症相关基因在中国的表达 胎盘在出生时和产后6周有EPDS评分。在目标2中，我们将研究这种关联 血中细胞因子水平(IL-1b、IL-17A、IL-6、CRP)与SARS-CoV-2相关胎盘基因和 产后抑郁(EPDS评分)在出生时和产后6周。最后，在目标3中，我们将验证密钥 利用定量基因表达谱分析胎盘样本中AIM 1和AIM 2的发现/候选基因 (QPCR)。

Summary The placenta is an integral organ during pregnancy, being a regulator of the in-utero environment including maternal neuroendocrine changes. Previous efforts have begun to elucidate a connection between HPA-axis gene expression in the placenta and maternal mental health, implicating that dysregulation of gene expression in the placenta has potential consequences for both the physical and mental health of the pregnant individual. Fully interrogating this connection is imperative, and there is an urgent need to expand our understanding of the role placental gene expression plays. This is especially important in the context of the coronavirus disease 2019 (covid-19) pandemic, as infections and the inflammatory responses they elicit have the potential to have a negative effect on maternal mental health. The parent study (Generation-CSF) is currently using a large ongoing pregnancy cohort to investigate the impact of SARS-CoV-2 infection and subsequent inflammatory changes on maternal mental health and cognition through paired blood and CSF (Cerebrospinal fluid) samples and psychiatric and cognitive assessments during and after pregnancy. This supplement aims to expand upon this investigation by clarifying the role that the placenta, as a regulator of neuroendocrine chances, could be playing in this relationship. By utilizing already collected placental samples and existing RNAseq data to investigate immune and inflammation genes in the placenta, which have yet to be explored in connection to maternal mental health, this supplement provides important additional information about what could be driving the proposed negative system wide changes that occur after infection during pregnancy. We hypothesize that SARS-CoV-2 infection during pregnancy will be positively associated with the expression of immune and inflammation markers in the placenta and maternal blood and that this upregulation will serve as a driver for increased EPDS scores at birth and at 6 weeks postpartum. In Aim 1 we will examine the association between SARS-CoV-2 infection and the expression of a curated list of 497 immune and inflammation related genes in the placenta with EPDS scores at birth and 6 weeks postpartum. In Aim 2 we will examine the association between cytokine levels in the blood (Il-1b, Il-17A, Il-6, CRP) and placental genes linked to SARS-CoV-2 and postpartum depression (EPDS scores) at birth and at 6 weeks postpartum. Finally, in Aim 3 we will validate key findings/candidate genes from Aim 1 and 2 in placental samples using quantitative gene expression profiling (qPCR).