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

该项目旨在研究出生前和出生后的儿童因素，并在西澳大利亚怀孕队列研究(RAINE研究)中检查它们与HPA功能、认知和青春期心理健康的关系。儿童期接触不仅包括儿童时期的应激性生活事件、家庭功能和心理健康状况的轨迹，而且还包括宫内和出生后成长模式的影响，以及一系列全面的心理社会、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，并检查它们与早期生命暴露的相互作用及其神经生物学后果。我们还将测试16岁的Raine受试者的认知能力，在一些受试者中，我们将在执行这些测试时对他们的大脑活动进行成像。随着RAINE队列的成熟，我们期望为未来的神经科学研究增加已经全面的表型RAINE研究数据库，提供神经生物学信息。我们假设，童年时期早期生活压力、家庭功能障碍或精神健康不良的持续增加的轨迹将增加RAine研究青少年经历以下情况的风险：(I)青春期更高的基线皮质醇水平增加压力敏感性；(Ii)如果青少年携带特定单倍型的糖皮质激素和盐皮质激素受体基因，则青少年压力敏感性增加；(Iii)青春期抑郁，如果他们是5-HTT基因短等位基因的纯合或杂合；(Iv)--根据功能磁共振成像的测量，在认知测试期间，认知表现较差，非典型的非前额叶皮质(PFC)大脑活动增加；及(V)-青春期出现更多心理健康问题。

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.