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

总结 胎盘是怀孕期间的一个完整器官，是子宫内环境的调节器，包括 母体神经内分泌变化。以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体的心理健康，暗示基因表达失调 胎盘中的残留物对怀孕个体的身体和精神健康都有潜在的影响。 充分探究这一联系势在必行，迫切需要扩大我们对 胎盘基因表达的作用。这在冠状病毒病的背景下尤为重要 2019年（COVID-19）大流行，因为它们引起的感染和炎症反应有可能导致 对产妇的心理健康有负面影响。母研究（Generation-CSF）目前正在使用大型 正在进行的妊娠队列研究SARS-CoV-2感染和随后的炎症反应的影响 通过配对血液和CSF（脑脊液）样本观察产妇心理健康和认知的变化 以及怀孕期间和之后的精神和认知评估。本补充旨在扩大 这项研究通过阐明胎盘作为神经内分泌调节因子的作用， 在这段感情中扮演角色通过利用已经收集的胎盘样品和现有的RNAseq数据， 研究胎盘中的免疫和炎症基因，这些基因尚未被探索， 产妇心理健康，这一补充提供了重要的额外信息，什么可以驱动 妊娠期间感染后发生的拟议的系统范围内的负面变化。我们假设 妊娠期SARS-CoV-2感染与免疫原性表达呈正相关， 胎盘和母体血液中的炎症标志物，这种上调将作为一个驱动因素， 出生时和产后6周EPDS评分增加。在目标1中，我们将研究 SARS-CoV-2感染和497个免疫和炎症相关基因的表达 在出生时和产后6周用EPDS评分法对胎盘进行评分。在目标2中，我们将研究 血液中的细胞因子水平（IL-1b、IL-17 A、IL-6、CRP）和与SARS-CoV-2相关的胎盘基因之间的关系， 产后抑郁症（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 使用定量基因表达谱分析胎盘样本中Aim 1和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).