LONGITUDINAL ASSOCIATIONS OF STRESS EXPOSURE, CORTISOL, AND THE BRAIN

本建议建立在我们12年对儿童和家庭的纵向研究以及我们与Davidson、Goldsmith和Kalin合作的历史基础上。通过威斯康星州对家庭和工作的研究，我们跟踪了从出生前到儿童后期(五年级)的家庭，并跟踪了儿童在情感风格上的个体差异，最显著的是反复观察儿童的情绪反应和唾液皮质醇的调节和采样 4 1/2和3年级和5年级。计划研究的主要背景是我们最近的发现 皮质醇水平在41/2岁时最高的儿童在婴儿期和学龄前阶段都暴露于更大的压力(尤其是母亲的抑郁)，当时皮质醇被采样，而且皮质醇可以预测幼儿园和1、3、5年级的精神症状。与临床前动物研究和其他人类研究一致，我们的发现表明，早期应激可能会使儿童的HPA系统和 情绪反应更容易受到后来的压力的影响。我们将跟踪这些儿童直到九年级，以进一步调查先前和持续的压力暴露和情绪反应对精神症状/障碍、认知功能、大脑形态测量和参与情绪调节的大脑回路的影响。中心结构提供的协作和研究资源使我们能够将最新的 艺术成像和荷尔蒙评估，包括行为、情感、认知和社会功能的纵向测量。主要目的是1)调查儿童基础皮质醇的纵向模式与他们的应激暴露史、情绪反应和调节、认知功能和内化问题的过程的关系；2)调查青少年早期大脑形态计量变异的个体差异(重点是PFC、杏仁核、海马体)，以及与应激暴露的纵向模式、基础皮质醇、情绪反应和调节以及认知功能的关系；3)使用功能成像来评估与情绪和情绪调节相关的关键结构的响应度的个体差异，因为它们与行为表型和内化有关。这些研究提供了一个前所未有的机会，将行为科学和神经科学方法结合起来，开始阐明儿童/青少年心理健康问题所涉及的关键机制。

The present proposal builds on our 12-year longitudinal study of children and families and our history of collaboration with Davidson, Goldsmith and Kalin. Through the Wisconsin Study of Families and Work we have followed families from before birth to late childhood (Grade 5) and have tracked children's individual differences in affective style, most notably repeated observations of emotional reactivity and regulation and sampling of salivary cortisol at age 4 1/2 and Grades 3 and 5. The main context for the planned studies is our recent finding that children with the highest basal cortisol levels at age 41/2 had been exposed to greater stress (especially maternal depression) both in infancy and in the preschool period when cortisol was sampled, and further that the cortisol predicted psychiatric symptoms in Kindergarten and Grades 1, 3, and 5. Consistent with preclinical animal studies and other human studies, our findings suggest that early stress may sensitize children's HPA systems and emotional responses to be more vulnerable to later stress. We will follow the children through Grade 9 to further investigate consequences of prior and ongoing stress exposure and emotional reactivity for psychiatric symptoms/disorders, cognitive functioning, brain morphometry, and the brain circuitry involved in emotion regulation. The collaboration and research resources afforded by a Center structure allow us to integrate state-of-the- art imaging and hormonal assessments with longitudinal measures of behavioral, emotional, cognitive, and social functioning. Major aims are 1) to investigate associations of children's longitudinal patterns of basal cortisol with their history of stress exposure, emotional reactivity and regulation, cognitive functioning, and course of internalizing problems; 2) to investigate individual differences in morphometric variation (with a focus on PFC, amygdala, hippocampus) of early adolescents' brains, and associations with longitudinal patterns of stress exposure, basal cortisol, emotional reactivity and regulation, and cognitive functioning; and 3) to use functional imaging to assess individual differences in responsivity of key structures associated with emotion and emotion regulation as they relate to the behavioral phenotype, internalizing. These studies provide an unprecedented opportunity to integrate behavioral and neuroscience approaches to begin to elucidate key mechanisms involved in the mental health problems of children/adolescents.