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: 10406368
• 负责人: Nadine M. Melhem
• 金额: $ 72.06万
• 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/10406368
• 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 (Brain); 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; base; biological adaptation to stress; biological systems; caregiving; early childhood; early life stress; hypothalamic-pituitary-adrenal axis; improved; middle childhood; neural circuit; novel; peer; psychiatric symptom; recruit; relating to nervous system; 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.

早期的生活压力与长期持续到成年的精神疾病的风险增加有关。