A national birth cohort study of prenatal factors and neurodevelopmental psychiatric disorders

在这份重新提交的申请中，我们寻求评估母体氧化应激的生物标记物与 子代精神分裂症(SZ)和自闭症谱系障碍(ASD)及其相互关系 在开发过程中暴露在其他环境中。这项建议是基于芬兰的产前检查 精神分裂症研究(FIPS-S)和自闭症研究(FIPS-A)--最大的产前血清流行病学研究 迄今为止，在这些疾病中的暴露，以及第一个利用国家出生队列的人。这种嵌套病例对照 这项研究利用了芬兰产妇队列(FMC)，该队列包括芬兰几乎所有从 1987-2017年；总样本量约为100万。采集孕妇产前血清样本 并从每个孕妇那里存档，芬兰精神病学登记处包含SZ和SZ的有效诊断 芬兰几乎所有住院和非住院病例的自闭症。我们已经确定了大量的样本 SZ和ASD病例和对照后代以及几个产前生物标志物之间的关系 而这群人中的这些障碍。尽管母体氧化应激会导致胎儿发育异常，但 与发育侮辱有关，并导致符合SZ和SZ的大脑和行为异常 ASD，以前没有研究过这种产前因素与精神疾病之间的关系 子代的诊断结果。我们的目标是解决母亲暴露在氧化应激和 通过对大量病例和孕妇孕期血清样本的分析，发现了这些疾病 配对对照后代。我们将检验母体抗氧化防御的生物标志物的假设 系统与子代SZ和ASD呈负相关，而促氧化生物标志物呈正相关 与这些结果相关。我们还将评估观察到的这些母体之间的相关性 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记物与SZ/ASD之间的关系。 为此，将分析来自深圳和ASD病例和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对产前的更好的理解 SZ和ASD的危险因素。由于氧化应激是一种常见的致病机制，由 与这些疾病有关的几种类型的环境侮辱，研究提供了 通过减少这些暴露来预防它们的可能性，并可能提出新的致病机制 未来的翻译研究。总而言之，拟议的工作建立在现有的全国出生队列的基础上，并 预计将影响一个新兴的、具有潜在变革性的流行病学研究领域 临床/基础神经科学，导致公共卫生政策的改进。

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.