Prenatal Maternal Stress, Exposure to Environmental Chemicals, and Cognitive Development: Potential Roles for Inflammation and the Developing Gut Microbiome
产前母亲压力、环境化学物质暴露和认知发展:炎症和肠道微生物群发育的潜在作用
基本信息
- 批准号:10536059
- 负责人:
- 金额:$ 70.69万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2022
- 资助国家:美国
- 起止时间:2022-08-22 至 2027-04-30
- 项目状态:未结题
- 来源:
- 关键词:4 year oldActivities of Daily LivingAddressAgeAmericanAncillary StudyArchivesAreaBiologicalBloodBrainCOVID-19 pandemicChemical ExposureChildChild DevelopmentChild HealthCognitionCognitiveCommunitiesConceptionsDevelopmentDiffusion Magnetic Resonance ImagingDistressEmotionalEnvironmental PollutionEpidemiologyEpinephrineExposure toFamilyFirst Pregnancy TrimesterHealthHealth PrioritiesHeavy MetalsIceImageInflammationInflammatoryInterventionInterviewKnowledgeLinkMagnetic Resonance ImagingMeasuresMediatingMediator of activation proteinMethodsMichiganMothersNatural DisastersNatural experimentNeuritesNewborn InfantNorepinephrineNutritionalOutcomePaperParentsPartner in relationshipPathway interactionsPatternPhenotypePlacentaPlasmaPolychlorinated BiphenylsPrefrontal CortexPregnancyProbabilityProcessProtocols documentationPsychosocial StressResearchRestRisk FactorsRoleSamplingSecond Pregnancy TrimesterShotgunsSpottingsStressStructureSurfaceSystemTestingThickTimeToxicant exposureUnited States National Institutes of HealthUrban CommunityUrineWomanbasecognitive developmentcohortcritical periodenvironmental chemicalfetalfunctional MRI scangut microbiomegut-brain axishigh riskhigh risk infantimprovedimproved outcomeindexinginflammatory markermaternal serummaternal stressmetagenomemetagenomic sequencingmicrobialmicrobiomemicrobiome researchmigrationmultidisciplinarymultimodal neuroimagingmyelinationneural circuitneurocognitive testneurogenesisneuroimagingnovel strategiesnovel therapeutic interventionoffspringpostnatalprenatalprenatal exposureprenatal stresspsychosocialpsychosocial stressorsrecruitrelating to nervous systemstressorsuburburban areavulnerable communitywhite matter
项目摘要
PROJECT SUMMARY
Children in distressed urban communities have a disproportionally high risk for cognitive delays due to both
biological and psychosocial exposures. Developing strategies to support cognitive development in these vulner-
able communities is an urgent health priority but is hampered by a lack of knowledge regarding the mechanisms
responsible for these epidemiological patterns. Our project will address this gap, by focusing on 2 types of ex-
posures (psychosocial stress and environmental contaminants) and 2 potential mechanistic pathways (inflam-
mation and the gut microbiome), which are potentially modifiable. Our central hypothesis is that these pathways
alter neurodevelopmental processes (including neurogenesis, neural migration, neurite outgrowth, myelination,
and the assembly of functional brain networks) and act as important mediators between psychosocial stress/en-
vironmental contaminant exposure and cognitive development. We will test this hypothesis via 3 specific aims:
(1) Determine whether psychosocial stress, including from the COVID-19 pandemic, influences cognitive devel-
opment via altered inflammatory profiles and patterns of gut microbiome development. (2) Determine whether
exposure to environmental contaminants (heavy metals & polychlorinated biphenyls) influences cognitive devel-
opment via altered inflammatory profiles and the microbiome. (3) Identify neural circuits involved in these mech-
anistic pathways via state-of-the-art multimodal neuroimaging of 4-year-old children. The proposed study will
capitalize on an existing, probability-based statewide pregnancy cohort that will eventually include 1,100 women
and their offspring. Measures of prenatal maternal stress and chemical exposures will be available via the parent
study. We also have access to maternal serum and urine, placentas, newborn blood spots, interviews with moth-
ers on health and development at 3, 9, and 24 months and a 3-month fecal sample. We will recruit 300 children
into this ancillary study, adding longitudinal fecal sampling and neurocognitive testing (Differential Ability Scales-
II) and neuroimaging at 4 years of age. Recruitment will focus on families in distressed urban areas and suburban
areas with lower levels of environmental contaminant exposure for comparison. We will analyze inflammatory
markers in maternal serum and newborn blood spots, perform shotgun metagenomics sequencing on approxi-
mately 1000 fecal samples, and analyze epinephrine and norepinephrine in 900 maternal urine samples, col-
lected at three points in pregnancy, as an objective measure of stress. Imaging will include structural MRI, diffu-
sion tensor imaging (DTI), and resting state fMRI scans. We will generate measures of subcortical structure
volumes, global and regional cortical thickness and surface area, white matter microstructure, and functional
brain connectivity to address our aims. This multi-disciplinary proposal will have a positive impact because it will
substantially advance our understanding of the biological mechanisms by which psychosocial stressors and
environmental chemicals influence cognitive development and lay the groundwork for developing interventions
to mitigate the impact of these exposures by targeting inflammatory pathways and/or the microbiome.
项目总结
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Rebecca Knickmeyer其他文献
Rebecca Knickmeyer的其他文献
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{{ truncateString('Rebecca Knickmeyer', 18)}}的其他基金
Does microbiome composition moderate GI and CNS function in a VPA-induced mouse model of autism?
在 VPA 诱导的自闭症小鼠模型中,微生物组组成是否会调节胃肠道和中枢神经系统功能?
- 批准号:
10753699 - 财政年份:2023
- 资助金额:
$ 70.69万 - 项目类别:
Prenatal Maternal Stress, Exposure to Environmental Chemicals, and Cognitive Development: Potential Roles for Inflammation and the Developing Gut Microbiome
产前母亲压力、环境化学物质暴露和认知发展:炎症和肠道微生物群发育的潜在作用
- 批准号:
10688283 - 财政年份:2022
- 资助金额:
$ 70.69万 - 项目类别:
Genetic Influences on Infant Brain Development: Understanding the Developmental Origins of Mental Illness
遗传对婴儿大脑发育的影响:了解精神疾病的发育起源
- 批准号:
10406290 - 财政年份:2021
- 资助金额:
$ 70.69万 - 项目类别:
Genetic Influences on Infant Brain Development: Understanding the Developmental Origins of Mental Illness
遗传对婴儿大脑发育的影响:了解精神疾病的发育起源
- 批准号:
10596195 - 财政年份:2021
- 资助金额:
$ 70.69万 - 项目类别:
Genetic Influences on Infant Brain Development: Understanding the Developmental Origins of Mental Illness
遗传对婴儿大脑发育的影响:了解精神疾病的发育起源
- 批准号:
10217435 - 财政年份:2021
- 资助金额:
$ 70.69万 - 项目类别:
The Development of Gut Microbiota and Behavioral Inhibition in Childhood: The Role of Early Stress and Brain Development
肠道菌群的发育和儿童时期的行为抑制:早期压力和大脑发育的作用
- 批准号:
10673754 - 财政年份:2020
- 资助金额:
$ 70.69万 - 项目类别:
The Development of Gut Microbiota and Behavioral Inhibition in Childhood: The Role of Early Stress and Brain Development
肠道菌群的发育和儿童时期的行为抑制:早期压力和大脑发育的作用
- 批准号:
10439815 - 财政年份:2020
- 资助金额:
$ 70.69万 - 项目类别:
The Development of Gut Microbiota and Behavioral Inhibition in Childhood: The Role of Early Stress and Brain Development
肠道菌群的发育和儿童时期的行为抑制:早期压力和大脑发育的作用
- 批准号:
10266177 - 财政年份:2020
- 资助金额:
$ 70.69万 - 项目类别:
GUT MICROBIOTA AND ANXIETY: A MECHANISTIC STUDY OF HUMAN INFANTS
肠道微生物群和焦虑:人类婴儿的机制研究
- 批准号:
8755142 - 财政年份:2014
- 资助金额:
$ 70.69万 - 项目类别:
GUT MICROBIOTA AND ANXIETY: A MECHANISTIC STUDY OF HUMAN INFANTS
肠道微生物群和焦虑:人类婴儿的机制研究
- 批准号:
8880291 - 财政年份:2014
- 资助金额:
$ 70.69万 - 项目类别:
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