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: 10885448
• 负责人: Nadine M. Melhem
• 金额: $ 11.35万
• 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/10885448
• 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.

早期生活压力与精神疾病的风险增加有关，这种疾病会长期持续到成年。 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 童年早期发生的压力生活经历为生物调节失调奠定了基础 使儿童面临精神病理学风险的压力反应。我们的首要目标是检查 早期生活压力影响幼儿期精神病理学风险的生物学途径，以及 哪些护理可以改变生物和心理应激反应。我们拟招募150名儿童， 4-6岁，父母离婚后3个月内（压力组）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。压力和控制儿童将在 6 个月和 18 个月大时进行随访 之后。我们选择离婚作为压力源，因为它在幼儿期很常见；代表着恶化 多重压力的家庭过程；扰乱护理环境；并且与内化有关 并将儿童的问题和长期的精神病理学外化。这个人口将使我们能够研究 压力反应的展开，这对于其他更严重的压力源来说几乎是不可能捕捉到的。我们 重点关注4-6岁这一时期，因为这是神经可塑性增强的时期，也是一个过渡期 从家庭到同伴和老师的关系，这使得孩子对压力源特别敏感， 扰乱他们的护理环境。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 轴活性的回顾性测量； 2）唾液皮质醇，衡量 当前 HPA 轴活动； 3) 与压力有关的区域的 MRI 结构和功能连接 回应。我们将评估离婚前因素（例如，父母的精神病理学史、父母冲突）， 使用自我报告和生物学措施进行离婚后父母调整（HCC）；亲子行为和 大脑同步性，亲子关系的生物学衡量标准；其他离婚后因素（例如，持续的 冲突）;以及儿童的内化和外化症状。我们假设压力组会 离婚后早期表现出较高的 HCC、唾液皮质醇以及结构和功能连接 与对照组儿童相比；离婚前的因素会缓和这些关系。压力组 随着时间的推移，将显示出 HCC、唾液皮质醇以及结构和功能连接性的下降；和父母的 皮质醇减少，精神症状增加，亲子行为和大脑下降 同步性和其他离婚后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 研究幼儿时期压力反应的神经生物学，并将提高我们对压力反应的理解 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 尽早发现处于危险中的儿童，并指导新的基于生物学的预防和干预方法。

项目成果

Combined Transplantation of Human MSCs and ECFCs Improves Cardiac Function and Decrease Cardiomyocyte Apoptosis After Acute Myocardial Infarction.

人间充质干细胞和ECFC联合移植可改善急性心肌梗塞后的心脏功能并减少心肌细胞凋亡。

• DOI: 10.1007/s12015-022-10468-z
• 发表时间: 2023
• 期刊: Stem cell reviews and reports
• 影响因子: 4.8
• 作者: Tripathi,Himi;Domingues,Alison;Donahue,Renee;Cras,Audrey;Guerin,CoralieL;Gao,Erhe;Levitan,Bryana;Ratajczak,MariuszZ;Smadja,DavidM;Abdel-Latif,Ahmed;Tarhuni,WadeaM
• 通讯作者: Tarhuni,WadeaM

Autologous CD133 + Cells and Laser Revascularization in patients with severe Ischemic Cardiomyopathy.

自体 CD133--细胞和激光血运重建治疗严重缺血性心肌病。

• DOI: 10.1007/s12015-022-10479-w
• 发表时间: 2023
• 期刊: Stem cell reviews and reports
• 影响因子: 4.8
• 作者: Abdel-Latif,Ahmed;Ahmed,Taha;Leung,SteveW;Alnabelsi,Talal;Tarhuni,Wadea;Sekela,MichaelE
• 通讯作者: Sekela,MichaelE

Inflammasome activation promotes venous thrombosis through pyroptosis.

炎症小体激活通过细胞焦亡促进静脉血栓形成。

• DOI: 10.1182/bloodadvances.2020003041
• 发表时间: 2021
• 期刊: Blood advances
• 影响因子: 7.5
• 作者: Zhang,Yan;Cui,Jian;Zhang,Guoying;Wu,Congqing;Abdel-Latif,Ahmed;Smyth,SusanS;Shiroishi,Toshihiko;Mackman,Nigel;Wei,Yinan;Tao,Min;Li,Zhenyu
• 通讯作者: Li,Zhenyu