LONGITUDINAL ASSOCIATIONS OF STRESS EXPOSURE, CORTISOL, AND THE BRAIN

目前的建议建立在我们对儿童和家庭的12年纵向研究以及我们与戴维森、金匠和卡林的合作历史的基础上。通过威斯康星州的家庭和工作研究，我们跟踪了从出生前到儿童后期（5年级）的家庭，并跟踪了儿童情感风格的个体差异，最显着的是对情绪反应和调节的重复观察以及年龄时唾液皮质醇的采样 4 1/2和3、5级。计划研究的主要背景是我们最近的发现 41岁半时基础皮质醇水平最高的儿童在婴儿期和学龄前时期都暴露于更大的压力（特别是母亲抑郁症），皮质醇可以预测幼儿园和1年级，3年级和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，我们的研究结果表明，早期压力可能使儿童的HPA系统敏感， 更容易受到后期压力的影响。我们将跟踪儿童到9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，脑形态测量和参与情绪调节的脑回路的影响。中心结构提供的合作和研究资源使我们能够整合国家的， 艺术成像和激素评估，以及行为、情感、认知和社会功能的纵向测量。主要目的是：（1）探讨儿童基础皮质醇水平的纵向变化与其应激史、情绪反应和调节、认知功能和内化问题的关系; 2）研究形态变异的个体差异（重点关注前额叶皮质、杏仁核、海马体），以及与压力暴露纵向模式、基础皮质醇，情绪反应和调节，以及认知功能; 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反应性的个体差异，因为它们与行为表型，内化有关。这些研究提供了一个前所未有的机会，整合行为和神经科学的方法，开始阐明儿童/青少年心理健康问题的关键机制。

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.