Chronic stress and executive function in children: a neuroimaging study of twins

 描述(申请人提供)：儿童早期的慢性压力经历，如家庭贫困、邻里和学校混乱、家庭冲突，对一生的身心健康、学业成就以及最终的社会、教育和经济成就都会产生严重的负面影响。在这项建议中，我们将重点放在神经生物学机制上，这些机制将与家庭、邻居和学校不利相关的慢性压力与学业成绩受损联系起来。我们假设，慢性压力和学业成绩之间的联系是通过皮质醇对执行功能的影响来调节的。执行功能是通过允许学习者暂时存储信息、适应任务要求和注意相关刺激来支持学习技能的调节过程。功能磁共振成像(FMRI)研究表明，儿童大脑在执行功能任务期间表现出特有的激活模式。这些区域中的许多都有高浓度的糖皮质激素受体。因此，与压力相关的皮质醇功能紊乱可能会影响执行功能的神经基础。皮质醇通常被概念化，S是环境压力效应的中介；然而，基因也影响皮质醇的功能。此前没有一项研究全面测试皮质醇-成就联系的潜在机制是否纯粹是环境因素，以及皮质醇是否是一种生理内表型，介导了基因对执行功能和学业成就的影响。这项拟议的研究将结合内分泌学和神经科学的尖端方法和技术，以及人类生态学和行为遗传学的成熟方法，探索慢性应激、皮质醇、执行功能和成就之间的联系。我们将从300对具有人口代表性的三年级双胞胎(150对，50%同卵)中收集社会生态学数据、头发皮质醇样本、执行功能数据和学校成绩单成绩结果，其中一半(75对中的150对N=150对双胞胎)将在执行执行功能任务期间参与fMRI扫描。这种高度创新和跨学科的方法将使我们能够：(1)测试头发皮质醇与关键研究变量-社会生态压力、执行功能和学业成就-之间的关联的大小和形状；(2)测试皮质醇和执行功能在压力和学习成绩之间的中介作用的多变量模型；以及(3)估计中介模型中确定的关键途径通过遗传和/或环境机制发生的程度。

 DESCRIPTION (provided by applicant): The experience of chronic stressors in early childhood, such as family poverty, neighborhood and school chaos, and family conflict have substantial negative consequences for life course physical and mental health, academic achievement, and ultimate social, educational, and economic attainment. With this proposal, we focus on neurobiological mechanisms that link chronic stress associated with family, neighborhood, and school disadvantage to impaired academic achievement. We hypothesize that the association between chronic stress and academic achievement is mediated by the effects of cortisol on executive functions. Executive functions are regulatory processes that support the acquisition of academic skills by allowing the learner to store information temporarily, adapt to task demands, and pay attention to relevant stimuli. Functional magnetic resonance imaging (fMRI) studies indicate that the child brain exhibits characteristic patterns of activation during executive functioning tasks. Many of these same regions have high concentrations of glucocorticoid receptors. Thus, stress-related disruptions in cortisol function are likely to affect the neural bases of executive functions. Cortisol is typically conceptualized s a mediator of the effects of environmental stress; however, genes also influence cortisol function. No previous study has comprehensively tested whether mechanisms underlying cortisol-achievement associations are purely environmental and whether, additionally or alternatively, cortisol is a physiological endophenotype that mediates genetic influences on executive functions and academic achievement. The proposed research will combine cutting-edge methods and technologies from endocrinology and neuroscience with well-developed methods from human ecology and behavioral genetics to explore the associations between chronic stress, cortisol, executive functions, and achievement. We will collect socioecological data, hair cortisol samples, executive function data, and school transcript achievement outcomes from a diverse and population-representative sample of 300 twins (150 pairs, 50% monozygotic) in grade 3, half of whom (N=150 twins from 75 pairs) will participate in fMRI scanning during performance of executive function tasks. This highly innovative and cross-disciplinary approach will allow us to: (1) Test the magnitude and shape of associations between hair cortisol and key study variables - socioecological stress, executive functions, and academic achievement; (2)Test a multivariate model of the mediating roles of cortisol and executive functions on the association between stress and achievement; and (3) Estimate the extent to which key pathways identified in the mediation model occur via genetic and/or environmental mechanisms.