A national birth cohort study of prenatal factors and neurodevelopmental psychiatric disorders
产前因素和神经发育精神疾病的全国出生队列研究
基本信息
- 批准号:10515652
- 负责人:
- 金额:$ 54.76万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2020
- 资助国家:美国
- 起止时间:2020-01-06 至 2024-10-31
- 项目状态:已结题
- 来源:
- 关键词:AddressAdverse effectsAntioxidantsArchivesAreaBehavioralBiological AssayBiological MarkersBirthBrainC-reactive proteinClinicalCohort StudiesCotinineDNADevelopmentDiagnosisDiagnosticDichlorodiphenyl DichloroethyleneDiseaseEnvironmental ExposureEtiologyEventExposure toFetal DevelopmentFinlandFundingFutureHealth PolicyHospitalizationInflammationInvestigationLipid PeroxidationLipidsMaternal ExposureMeasuresMediatingMediatorMental disordersNeonatalNested Case-Control StudyNeuronsNeurosciencesNitrogenOutcomeOxidative StressOxygenPathogenicityPesticidesPregnancyPreventionPreventiveProcessProliferatingProteinsPublic HealthReactive Oxygen SpeciesRegistriesResearchResourcesRiskRisk FactorsRoleSample SizeSamplingSchizophreniaSeroepidemiologic StudiesSerumSpecimenSuperoxide DismutaseSystemTestingThiobarbituric Acid Reactive SubstancesTrichloroethanesWorkautism spectrum disordercohortdisorder preventionearly life exposureepidemiology studyfetalfollow-upglutathione peroxidaseimprovedmaternal cigarette smokingmaternal riskmaternal serumneurodevelopmentneurotransmissionnoveloffspringoxidationoxidative damageperinatal complicationsprenatalprenatal exposureprenatal risk factorpublic health relevancesextherapeutic targettranslational studyvirtual
项目摘要
In this re-submitted application, we seek to evaluate maternal biomarkers of oxidative stress in relation to
schizophrenia (SZ) and autism spectrum disorders (ASD) in offspring, their relationships with one another, and
with other environmental exposures during development. The proposal is based on the Finnish Prenatal
Studies of Schizophrenia (FiPS-S), and Autism (FiPS-A), the largest seroepidemiologic studies of prenatal
exposures in these disorders to date, and the first to utilize a national birth cohort. This nested case-control
study draws on the Finnish Maternity Cohort (FMC), which consists of virtually all pregnancies in Finland from
1987-2017; the total sample size is approximately 1 million. Maternal prenatal serum samples were obtained
and archived from each gravida, and the Finnish psychiatric registries contain validated diagnoses of SZ and
ASD on virtually all hospitalized and non-hospitalized cases in Finland. We have identified large samples of
SZ and ASD case and control offspring and demonstrated relationships between several prenatal biomarkers
and these disorders in this cohort. Although maternal oxidative stress causes abnormal fetal development, is
associated with developmental insults, and leads to brain and behavioral abnormalities concordant with SZ and
ASD, no previous study has ever examined relationships between this prenatal factor and psychiatric
diagnostic outcomes in offspring. We aim to address the role of maternal exposure to oxidative stress and
these disorders by assays of maternal serum specimens in pregnancies from large samples of case and
matched control offspring. We will test the hypothesis that maternal biomarkers of the antioxidant defense
system are negatively associated with SZ and ASD in offspring and a pro-oxidant biomarker is positively
associated with these outcomes. We will also evaluate whether correlations observed between these maternal
biomarkers in control offspring are disrupted in SZ and ASD offspring. Moreover, we shall assess whether sex
and perinatal complications modify relationships between maternal oxidative stress biomarkers and SZ/ASD.
For this purpose, maternal serum samples from SZ and ASD cases and matched controls will be analyzed for
biomarkers of oxidative stress. This research has the potential to result in a better understanding of prenatal
risk factors for SZ and ASD. Since oxidative stress is a common pathogenic mechanism that is caused by
several types of environmental insults which have been implicated in these disorders, the study offers the
potential for their prevention by reducing these exposures and may suggest new pathogenic mechanisms in
future translational studies. In summary, the proposed work builds on an existing national birth cohort, and is
anticipated to impact an emerging and potentially transformative area of research epidemiology and
clinical/basic neuroscience, leading to improvements in public health policy.
在这份重新提交的申请中,我们寻求评估与以下因素相关的母体氧化应激生物标志物:
后代的精神分裂症 (SZ) 和自闭症谱系障碍 (ASD) 及其相互关系,以及
与开发过程中的其他环境暴露。该提案基于芬兰产前法
精神分裂症 (FiPS-S) 和自闭症 (FiPS-A) 的研究,最大的产前血清流行病学研究
迄今为止对这些疾病的暴露,并且是第一个利用全国出生队列的。这个嵌套的案例控制
这项研究借鉴了芬兰产妇队列 (FMC),该队列几乎涵盖了芬兰自
1987-2017;总样本量约为100万。获取母亲产前血清样本
并从每个孕妇存档,芬兰精神病学登记处包含经过验证的 SZ 和
芬兰几乎所有住院和非住院病例都有 ASD。我们已经确定了大样本
SZ 和 ASD 病例和对照后代以及几种产前生物标志物之间的关系
以及该队列中的这些疾病。虽然母体氧化应激会导致胎儿发育异常,但
与发育损伤相关,并导致与 SZ 一致的大脑和行为异常
自闭症谱系障碍(ASD),之前没有研究检验过这种产前因素与精神疾病之间的关系
后代的诊断结果。我们的目标是解决母亲暴露于氧化应激和
通过对来自大量病例样本的妊娠期母体血清样本进行分析来发现这些疾病
匹配的对照后代。我们将检验以下假设:抗氧化防御的母体生物标志物
系统与后代的 SZ 和 ASD 呈负相关,而促氧化生物标志物则呈正相关
与这些结果相关。我们还将评估这些母亲之间是否观察到相关性
对照后代中的生物标志物在 SZ 和 ASD 后代中被破坏。此外,我们将评估性别是否
围产期并发症改变了母体氧化应激生物标志物与 SZ/ASD 之间的关系。
为此,将对来自 SZ 和 ASD 病例以及匹配对照的母体血清样本进行分析
氧化应激的生物标志物。这项研究有可能使人们更好地了解产前
SZ 和 ASD 的危险因素。由于氧化应激是一种常见的致病机制,
与这些疾病有关的几种环境侵害,该研究提供了
通过减少这些暴露来预防它们的潜力,并可能提出新的致病机制
未来的转化研究。总之,拟议的工作建立在现有的全国出生队列的基础上,并且是
预计将影响流行病学研究的新兴和潜在变革领域
临床/基础神经科学,导致公共卫生政策的改进。
项目成果
期刊论文数量(0)
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Alan Stewart Brown其他文献
Alan Stewart Brown的其他文献
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{{ truncateString('Alan Stewart Brown', 18)}}的其他基金
A national birth cohort study of prenatal factors and neurodevelopmental psychiatric disorders
产前因素和神经发育精神疾病的全国出生队列研究
- 批准号:
10294956 - 财政年份:2020
- 资助金额:
$ 54.76万 - 项目类别:
A national birth cohort study of prenatal factors and neurodevelopmental psychiatric disorders
产前因素和神经发育精神疾病的全国出生队列研究
- 批准号:
10080728 - 财政年份:2020
- 资助金额:
$ 54.76万 - 项目类别:
A national birth cohort study of prenatal factors and neurodevelopmental psychiatric disorders
产前因素和神经发育精神疾病的全国出生队列研究
- 批准号:
9916546 - 财政年份:2020
- 资助金额:
$ 54.76万 - 项目类别:
Maternal exposure to antidepressants and psychiatric outcomes among offspring in a national birth cohort.
全国出生队列中母亲接触抗抑郁药物和后代的精神病结果。
- 批准号:
10053685 - 财政年份:2018
- 资助金额:
$ 54.76万 - 项目类别:
Maternal exposure to antidepressants and psychiatric outcomes among offspring in a national birth cohort.
全国出生队列中母亲接触抗抑郁药物和后代的精神病结果。
- 批准号:
10308018 - 财政年份:2018
- 资助金额:
$ 54.76万 - 项目类别:
Prenatal Factors in Autism and other Psychiatric Outcomes in a National Birth Cohort
全国出生队列中自闭症和其他精神病结果的产前因素
- 批准号:
10005353 - 财政年份:2017
- 资助金额:
$ 54.76万 - 项目类别:
Prenatal Factors in Autism and other Psychiatric Outcomes in a National Birth Cohort
全国出生队列中自闭症和其他精神病结果的产前因素
- 批准号:
10251887 - 财政年份:2017
- 资助金额:
$ 54.76万 - 项目类别:
Prenatal factors and risk of autism in a Finnish national birth cohort
芬兰全国出生队列中的产前因素和自闭症风险
- 批准号:
7845977 - 财政年份:2009
- 资助金额:
$ 54.76万 - 项目类别:
Prenatal factors and risk of autism in a Finnish national birth cohort
芬兰全国出生队列中的产前因素和自闭症风险
- 批准号:
9063197 - 财政年份:2009
- 资助金额:
$ 54.76万 - 项目类别:
Prenatal factors and risk of autism in a Finnish national birth cohort
芬兰全国出生队列中的产前因素和自闭症风险
- 批准号:
8960823 - 财政年份:2009
- 资助金额:
$ 54.76万 - 项目类别:
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