Biological Substrates of Maladaptive Stress Response in Early Childhood

早期生活压力与精神障碍的风险增加有关，精神障碍会长期持续到成年。 大部分研究都集中在儿童期中期和青春期，然而，越来越多的证据表明 童年早期的紧张生活经历为生物调节失调奠定了基础 将儿童置于精神病态风险中的压力反应。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风险的生物学途径，以及 哪种照顾方式可以改变生理和心理上的压力反应。我们计划招募150名儿童， 4-6岁，父母离婚后3个月内(应激组)，并与75名对照组儿童进行比较 来自没有父母离婚史的家庭。压力和对照儿童将在6个月和18个月时接受跟踪调查。 后来。我们选择离婚作为压力源是因为它在幼儿时期很常见；代表着 多重有压力的家庭过程；破坏照看环境；与内化有关 以及儿童的外在问题和长期的精神病态。这群人将使我们能够研究 压力反应的展开，这是其他更严重的压力源几乎不可能捕捉到的。我们 把重点放在4-6年，因为这是神经可塑性增强的时期和过渡期 从家庭到同龄人和老师的关系，这使孩子对可能 打乱他们的照看环境。我们使用以下方法评估生物应激反应：1)头发皮质醇 浓度(Hcc)，慢性HPA轴活动的回溯性测量；2)唾液皮质醇，测量 当前HPA轴活动；3)应激相关区域的MRI结构和功能连通性 回应。我们将评估离婚前的因素(例如，父母有精神病病史、父母冲突)， 使用自我报告和生物测量(HCC)的离婚后父母适应；亲子行为和 大脑同步性，亲子关系的生物学测量；离婚后的其他因素(例如，持续的 冲突)；儿童症状的内在化和外在化。我们假设应激组会 离婚后早期表现出较高的肝细胞癌、唾液皮质醇以及结构和功能连接性 与控制孩子相比；离婚前的因素将缓和这些关系。应激组 随着时间的推移，会显示出肝癌、唾液皮质醇以及结构和功能连接性的降低； 皮质醇减少，精神症状增加，亲子行为和大脑减少 同步性和离婚后的其他因素将调解这些关系。最后，早期的生物反应 随着时间的推移，这些反应的变化将预测内化和外化症状。这项研究将 研究儿童早期应激反应的神经生物学，将增进我们对 早期生活应激影响精神病理风险的生物学机制。它将有助于识别 儿童早期处于危险之中，并指导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.