Biological Substrates of Maladaptive Stress Response in Early Childhood

幼儿期适应不良应激反应的生物基础

• 批准号: 10626021
• 负责人: Nadine M. Melhem
• 金额: $ 69.27万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-01 至 2025-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10626021
• 关键词: Adolescence; Adult; Affect; Age; Amygdaloid structure; Animals; Area; Behavior; Behavioral; Biological; Brain; Caregivers; Cessation of life; Child; Chronic; Chronic stress; Conflict (Psychology); Development; Divorce; Down-Regulation; Emotional; Environment; Exposure to; Family; Family Process; Foundations; Frequencies; Hair; Hippocampus; Human; Hydrocortisone; Hyperactivity; Institutionalization; Intake; Intervention; Magnetic Resonance Imaging; Measures; Mediating; Mental Health; Mental disorders; Modeling; Neurobiology; Neuronal Plasticity; Outcome; Parent-Child Relations; Parents; Pathway interactions; Patient Self-Report; Peripheral; Population; Prevention; Psychological Stress; Psychopathology; Race; Recording of previous events; Reporting; Research; Risk; Role; Salivary; Signal Transduction; Socioeconomic Status; Stress; Stressful Event; Symptoms; System; Temperament; Time; Translating; aged; biological adaptation to stress; biological systems; caregiving; comparison control; early childhood; early life stress; hypothalamic-pituitary-adrenal axis; improved; middle childhood; neural; neural circuit; neurodevelopment; novel; peer; psychiatric symptom; recruit; response; sex; stressor; teacher

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.

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。 但是，许多研究都集中在童年和青春期，但是有越来越多的证据 在幼儿期间发生的压力很大的生活经历为生物学失调的基础奠定了基础 压力反应使儿童有心理病理学风险。我们的总体目的是检查 生命早期压力会影响幼儿时期心理病理学风险的生物学途径，并通过 哪些护理可以改变生物学和心理压力反应。我们建议招募150名儿童 在父母离婚（压力组）的3个月内，年龄4-6岁，并将其与75名对照儿童进行比较 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个月中遵循 之后。我们选择离婚作为压力源，因为它在幼儿时期很常见。代表 多重压力的家庭过程；破坏护理环境；并与内部化有关 以及儿童的外在问题和持久的心理病理学。这个人口将使我们能够学习 压力反应的展开，几乎不可能捕获其他更严重的压力源。我们 专注于4 - 6年，因为它是神经可塑性的时期和过渡期 从家庭到同伴和老师的关系，这使得孩子对可能的压力特别敏感 破坏他们的护理环境。我们使用以下方式评估生物胁迫反应：1）头发皮质醇 浓度（HCC），这是慢性HPA轴活动的回顾性度量； 2）唾液皮质醇，量度 当前的HPA轴活动； 3）与压力有关的区域的MRI结构和功能连通性 回答。我们将评估分离前因素（例如，心理病理的父母历史，父母冲突）， 使用自我报告和生物学措施（HCC）的离婚后父母调整；亲子行为和 脑同步，对亲子关系的生物学度量；其他离婚后因素（例如， 冲突）;以及儿童内在化和外在症状。我们假设压力群将 在离婚后早期显示较高的HCC，唾液皮质醇以及结构和功能连接性 与对照儿童相比；而分离的因素将调节这些关系。压力组 随着时间的流逝，将显示HCC，唾液皮质醇以及结构和功能连通性的下降；和父母 减少皮质醇并增加精神病症状，并降低亲子的行为和大脑 同步和其他分支后因素将调解这些关系。最后，早期生物学反应 随着时间的流逝，这些反应的变化将预测内在化和外在症状。这项研究会 检查幼年时期压力反应的神经生物学，并将提高我们对 生命早期压力会影响精神病理风险的生物学机制。它将有助于识别 早期处于危险中的孩子，并指导新颖的基于生物学的预防和干预方法。