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

COVID-19 神经精神后遗症的脑脊液 (CSF) 和外周标志物：C-SF 一代妊娠研究

• 批准号: 10818133
• 负责人: Maria De Las Mercedes Perez Rodriguez
• 金额: $ 5.28万
• 依托单位: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-06-14 至 2024-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10818133
• 关键词: 2019-nCoV; Affect; Autoimmune; Automobile Driving; Biological; Biological Markers; Birth; Blood; Blood specimen; COVID-19 pandemic; Candidate Disease Gene; Cerebrospinal Fluid; Cognition; Data; Databases; Doctor of Philosophy; Environment; Foundations; Funding; Future; Gene Expression; Gene Expression Profiling; Generations; Genes; Genetic Transcription; Goals; Grant; Health; Immune; Immune response; Immunologic Markers; Individual; Infection; Inflammation; Inflammatory; Inflammatory Response; Investigation; Letters; Link; Maternal Health; Measures; Mental Health; Mentorship; Molecular Profiling; Neurobehavioral Manifestations; Neurosecretory Systems; Organ; Parents; Pathway interactions; Peripheral; Physicians; Placenta; Play; Postpartum Depression; Postpartum Period; Pregnancy; Process; Reproductive Health; Research; Role; SARS-CoV-2 exposure; SARS-CoV-2 infection; Sampling; Scientist; System; Tissues; Up-Regulation; career; cognitive testing; cohort; cytokine; differential expression; early pregnancy; experience; hypothalamic-pituitary-adrenal axis; in utero; inflammatory marker; neuropsychiatric sequelae of COVID-19; novel; offspring; parent grant; peripartum depression; physical conditioning; post SARS-CoV-2 infection; post pregnancy; pregnant; psychiatric symptom; transcriptome; transcriptome sequencing

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).

概括 胎盘是怀孕期间的整体器官，是UTERO环境的调节器 孕产妇神经内分泌。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性心理健康，暗示基因表达失调 在胎盘中，对怀孕个体的身心健康有潜在的后果。 充分询问这种联系是必须的，迫切需要扩大我们对 角色胎盘基因表达发挥作用。这在冠状病毒疾病的背景下尤其重要 2019年（COVID-19）大流行，因为感染和引起的炎症反应具有可能具有 对孕产妇心理健康的负面影响。家长研究（Generation-CSF）目前正在使用大型 持续的怀孕队列研究SARS-COV-2感染和随后的炎症的影响 通过配对的血液和CSF（脑脊液）样本的孕产妇心理健康和认知的变化 怀孕期间和之后的精神病和认知评估。这种补充旨在扩展 通过阐明胎盘作为神经内分泌机会的调节剂的作用，可以进行调查。 在这种关系中玩。通过利用已经收集的胎盘样本和现有RNASEQ数据到 研究胎盘中的免疫和炎症基因，这些基因尚未与 孕产妇心理健康，这种补充提供了有关可能驱动的重要信息 拟议的负面系统在怀孕期间感染后发生的巨大变化。我们假设这一点 怀孕期间的SARS-COV-2感染将与免疫的表达正相关 胎盘和孕妇血液中的炎症标记，这种上调将成为 出生时和产后6周的EPDS分数提高。在AIM 1中，我们将研究 SARS-COV-2感染以及497个免疫和炎症相关基因的精选列表的表达 EPDS出生时和产后6周的EPDS得分的胎盘。在AIM 2中，我们将检查协会 在血液中的细胞因子水平（IL-1B，IL-17A，IL-6，CRP）和与SARS-COV-2和SARS-COV-2相关的胎盘基因之间 产后抑郁症（EPDS得分）出生时和产后6周。最后，在AIM 3中，我们将验证密钥 使用定量基因表达谱图中的AIM 1和2的发现/候选基因 （qpcr）。