Biological Substrates of Maladaptive Stress Response in Early Childhood

早期生活压力与长期持续到成年的精神疾病风险增加有关。 大部分研究都集中在童年中期和青春期，然而，越来越多的证据表明， 儿童早期的压力生活经历为生物学功能失调奠定了基础。 压力反应会让孩子们有精神病的风险我们的首要目标是研究 早期生活压力影响儿童早期精神病理学风险的生物学途径， 这种刺激可以改变生物和心理的应激反应。我们计划招募150名儿童， 年龄4-6岁，父母离婚3个月内（压力组），并将他们与75名对照儿童进行比较 没有父母离异史的家庭压力和控制儿童将在6个月和18个月时进行随访 后我们选择离婚作为一种压力源，因为它在幼儿期很常见;代表着 多重压力的家庭过程;破坏了生存环境;并与内化有关 以及儿童的外化问题和长期的精神病理学。这些人口将使我们能够研究 压力反应的展开，这几乎是不可能捕捉到其他更严重的压力。我们 重点放在4-6年的时间段，因为这是一个神经可塑性增强的时期和过渡期 从家庭到同伴和老师的关系，这使得孩子们对压力源特别敏感， 破坏他们的生存环境。我们评估生物应激反应使用：1）头发皮质醇 浓度（HCC），慢性HPA轴活动的回顾性测量; 2）唾液皮质醇， 当前HPA轴活动;以及3）与应激有关的区域中的MRI结构和功能连接 应答我们将评估离婚前的因素（例如，父母精神病理学史、父母冲突）， 使用自我报告和生物测量（HCC）的离婚后父母调整;父母-子女行为和 大脑同步性，亲子关系的生物学测量;其他离婚后因素（例如，正在进行 冲突）;以及儿童的内化和外化症状。我们假设压力组 离婚后早期HCC、唾液皮质醇以及结构和功能连接性更高 与对照组儿童相比，离婚前的因素将缓和这些关系。应激组 随着时间的推移，HCC、唾液皮质醇以及结构和功能连接性降低; 皮质醇减少，精神症状增加，亲子行为和大脑 同步性和其他离婚后的因素将调解这些关系。最后，早期生物反应 这些反应随时间的变化将预测内化和外化症状。本研究将 研究儿童早期压力反应的神经生物学，将提高我们对 早期生活压力影响精神病理学风险的生物学机制。这将有助于识别 儿童基金会在早期就为处于危险中的儿童提供了指导，并指导了新的基于生物的预防和干预方法。

Early life stress is associated with increased risk for psychiatric disorders that is long lasting into adulthood. Much of the research has focused on middle childhood and adolescence, however, there is mounting evidence that stressful life experiences occurring in early childhood set the foundation for dysregulation in biological stress responses that put children at risk for psychopathology. Our overarching aims are to examine the biological pathways through which early life stress affects risk for psychopathology in early childhood, and by which caregiving can alter biological and psychological stress responses . We propose to recruit 150 children, aged 4-6 years, within 3 months of parental divorce (stress group) and compare them to 75 control children from families with no history of parental divorce. Stress and control children will be followed at 6 and 18 months later. We choose divorce as a stressor because it is common in early childhood; represents the exacerbation of multiple stressful family processes; disrupts the caregiving environment; and is associated with internalizing and externalizing problems and long-lasting psychopathology in children. This population will allow us to study the unfolding of stress responses, which is almost impossible to capture for other more severe stressors. We focus on the 4-6 years period because it is a period of heightened neural plasticity and a transitional period from family to peer and teacher relationships, which makes children especially sensitive to a stressor that could disrupt their caregiving environment. We assess biological stress responses using: 1) hair cortisol concentrations (HCC), a retrospective measure of chronic HPA axis activity; 2) salivary cortisol, a measure of current HPA axis activity; and 3) MRI structural and functional connectivity in areas implicated in stress responses. We will assess pre-divorce factors (e.g., parental history of psychopathology, parental conflict), post-divorce parental adjustment using self-report and biological measures (HCC); parent-child behavioral and brain synchrony, a biological measure of the parent-child relationship; other post-divorce factors (e.g., ongoing conflict); and internalizing and externalizing symptoms in children. We hypothesize that the stress group will show higher HCC, salivary cortisol, and structural and functional connectivity early on following divorce compared to control children; and that pre-divorce factors will moderate these relationships. The stress group will show decreased HCC, salivary cortisol, and structural and functional connectivity over time; and parental reduced cortisol and increased psychiatric symptoms and decreased parent-child behavioral and brain synchrony and other post-divorce factors will mediate these relationships. Finally, early biological responses and changes in these responses over time will predict internalizing and externalizing symptoms. This study will examine the neurobiology of stress responses in early childhood and will improve our understanding of the biological mechanisms through which early life stress affects risk for psychopathology. It will help identify children at risk early on and guide novel biologically-based prevention and intervention approaches.