Early life stress, adolescent brain development and risk for adverse cognitive and psychosocial outcomes

在西澳大利亚妊娠队列研究（Raine study）中，本项目旨在研究产前和产后儿童因素，并检查它们与青春期hpa功能、认知和心理健康的关系。童年暴露不仅包括童年时期压力生活事件的轨迹、家庭功能和心理健康状况，还包括宫内和产后生长模式的影响，以及一系列全面的社会心理、家庭和环境因素。我们的目标是描述与压力调节相关的基因的功能多态性，并研究它们与早期生活暴露及其神经生物学后果的相互作用。我们还将测试16岁的雷恩研究对象的认知能力，我们将对其中一些人在进行这些测试时的大脑活动进行成像。随着Raine队列的成熟，我们期望通过神经生物学信息来增强已经全面的表型Raine研究数据库，以用于未来的神经科学研究。我们假设，早期生活压力、家庭功能障碍或儿童时期心理健康状况不佳的增加和持续轨迹将增加Raine研究青少年经历的风险：(i) -青春期压力敏感性增加，基线皮质醇水平较高；（ii） -如果青少年携带糖皮质激素和矿皮质激素受体基因的特定单倍型，他们对压力的敏感性会增加；（iii）青春期抑郁症，如果他们是纯合或杂合的短等位基因的5-羟色胺转运体（5-HTT）基因；（iv） -在fMRI测量的认知测试中，认知表现较差，非典型非前额叶皮层（PFC）脑活动增加；（五）青春期的心理健康问题增多。

This project aims to study pre and postnatal childhood factors and examine their association with HPA-functioning, cognition, and mental health during adolescence in the Western Australian Pregnancy Cohort Study (Raine Study). Childhood exposures include not only trajectories of stressful life events, family functioning and mental health status during childhood, but also effects of intrauterine and postnatal growth patterns, and a comprehensive range of psychosocial, familial and environmental factors. It is our objective to characterise functional polymorphisms for genes related to stress regulation and examine their interactions with early life exposures and their neurobiological consequences. We will also test 16 year old Raine subjects for cognitive ability, and in some we will image their brain activity while performing these tests. We anticipate to enhance the already comprehensive phenotypic Raine Study data base with neurobiological information for future neuroscience studies as the Raine cohort matures. We hypothesise that increased and sustained trajectories of early life stress, family dysfunction or poor mental health during childhood will increase the risk of Raine Study adolescents experiencing: (i) - increased stress sensitivity with higher baseline cortisol levels during adolescence; (ii) - increased adolescent stress sensitivity, if they are carriers of specific haplotypes of the glucocorticoid and mineralocorticoid receptor genes.;(iii) - depression during adolescence, if they are homozygous or heterozygous for the short allele of the serotonin transporter (5-HTT) gene; (iv) - poorer cognitive performance and increased atypical non-prefrontal cortex (PFC) brain activity during cognitive testing as measured by fMRI; and (v) -more mental health problems during adolescence.