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

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,我们试图评估母体氧化应激的生物标志物, 精神分裂症(SZ)和自闭症谱系障碍(ASD)的后代,他们之间的关系, 在开发过程中与其他环境接触。该提案是根据芬兰产前 精神分裂症(FiPS-S)和自闭症(FiPS-A)的研究,产前最大的血清流行病学研究 迄今为止,这些疾病的暴露,以及第一个利用国家出生队列。这种嵌套的病例对照 这项研究借鉴了芬兰产妇队列(FMC),该队列由芬兰几乎所有的孕妇组成, 1987-2017年;总样本量约为100万。采集孕妇产前血清样本, 并从每个孕妇存档,芬兰精神病登记处包含SZ的有效诊断, 在芬兰,几乎所有住院和非住院病例的ASD。我们发现了大量的 SZ和ASD病例和对照后代,并证明了几种产前生物标志物之间的关系 和这些疾病的关系。虽然母体氧化应激导致胎儿发育异常, 与发育损伤相关,并导致与SZ一致的大脑和行为异常, ASD,以前的研究从未检查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的作用, 这些疾病的孕妇血清标本的分析,从大样本的情况下, 配对的对照后代。我们将检验母体抗氧化防御的生物标志物 系统与后代中SZ和ASD呈负相关,而促氧化生物标志物与后代中SZ和ASD呈正相关。 与这些结果有关。我们还将评估这些孕产妇之间是否存在相关性 对照后代中的生物标志物在SZ和ASD后代中被破坏。此外,我们将评估性行为是否 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,将分析SZ和ASD病例以及匹配对照的母体血清样本, 氧化应激的生物标志物。这项研究有可能导致更好地了解产前 深圳和ASD的风险因素。由于氧化应激是一种常见的致病机制, 几种类型的环境侮辱已牵连在这些疾病,该研究提供了 通过减少这些暴露,可能有预防的潜力,并可能提示新的致病机制, 未来的翻译研究总之,拟议的工作建立在现有的国家出生队列的基础上, 预计将影响流行病学研究的一个新兴和潜在的变革领域, 临床/基础神经科学,导致公共卫生政策的改善。

项目成果

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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:
    10515652
  • 财政年份:
    2020
  • 资助金额:
    $ 50.08万
  • 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:
    10294956
  • 财政年份:
    2020
  • 资助金额:
    $ 50.08万
  • 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:
    $ 50.08万
  • 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:
    $ 50.08万
  • 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:
    $ 50.08万
  • 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:
    $ 50.08万
  • 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:
    $ 50.08万
  • 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:
    $ 50.08万
  • 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:
    $ 50.08万
  • 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:
    $ 50.08万
  • 项目类别:

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