Mechanisms of resilience to developmental stress in children and adolescents.

儿童和青少年发展压力的恢复机制。

• 批准号: 9806213
• 负责人: Ran Barzilay
• 金额: $ 19.36万
• 依托单位: CHILDREN'S HOSP OF PHILADELPHIA
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-08-01 至 2023-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9806213
• 关键词: Adolescence; Adolescent; Adult; Age; Animals; Anxiety; Behavioral; Big Data; Biological; Biometry; Blood Cells; Brain; Child; Child Psychiatry; Child Traumatic Stress; Childhood; Clinical; Clinical Research; Cognitive; Communities; Computerized Medical Record; Cross-Sectional Studies; Data; Data Collection; Data Set; Depression and Suicide; Development; Development Plans; Disease; Early Intervention; Early identification; Educational workshop; Environment; Environmental Risk Factor; Epigenetic Process; Expert Systems; Exposure to; Family history of; Female; Fostering; Future; Gene Expression; Genetic; Genetic Predisposition to Disease; Genetic Risk; Genomics; Genotype; Glucocorticoids; Goals; Health; Human; Immune; Immune system; Individual; Inflammation; Inflammatory; Intervention; Investigation; Knowledge; Longevity; Measurable; Measures; Medical Records; Mental Depression; Mental Health; Mental disorders; Mentors; Mentorship; Methods; Mission; Moods; Neurocognitive; Neurosciences; Outcome; Participant; Pediatric Hospitals; Pennsylvania; Personal Satisfaction; Phenotype; Philadelphia; Physicians; Predisposition; Preventive; Preventive Intervention; Psyche structure; Psychiatrist; Psychopathology; Reporting; Research; Research Training; Resistance; Resources; Risk; Risk Estimate; Risk Factors; Risk stratification; Sampling; Scientist; Sex Differences; Statistical Data Interpretation; Stress; Suicide attempt; Supervision; Testing; Training; Translational Research; Trauma; Universities; Victimization; Youth; adverse outcome; anxiety symptoms; base; career; career development; child depression; childhood adversity; cognitive performance; cohort; design; early life adversity; executive function; expectation; experience; genetic variant; hands on research; improved; indexing; inflammatory marker; machine learning algorithm; multidisciplinary; predictive modeling; prevent; programs; prospective; psychologic; research clinical testing; resilience; screening; sex; stress related disorder; suicidal; suicidal behavior; trauma exposure

PROJECT SUMMARY/ ABSTRACT Children and adolescents often grow up in the face of substantial developmental stress (i.e. trauma). While for some, this shifts the developmental trajectory to that of mental and general health disorders, others are resilient. Most research on developmental psychopathology is focused on risk while little is known on the mechanisms that confer resilience. The current study aims to identify biological (genomic, immune), psychological and cognitive mechanisms that underpin resilience in youth as defined by having low mood- anxiety and suicidal outcomes in youth with substantial developmental stress exposure (i.e. trauma and family history of depression). Elucidating resilience mechanisms has huge clinical implications as it will improve stratification of risk to develop depression and/or suicidal behavior, and could identify biological, psychological and cognitive targets that can inform development of future preventive interventions aimed at promoting resilience, reducing the mental and general health adverse outcomes associated with childhood adversity. The study capitalizes on a large dataset of genotyped youths from the Philadelphia Neurodevelopmental Cohort (PNC), that have been comprehensively phenotyped for cognitive performance and psychopathology, and that reported substantial trauma exposure. The proposed research integrates genomic and cognitive data with clinical measures used to define resilience in cross sectional analysis of ~9500 PNC youths (Aim 1); incorporates longitudinal data of depression and suicide measures, pulled from electronic medical record in a subset of ~750 PNC youths (Aim 2); and relies on prospective data collection that includes immune profiling of selected PNC individuals to allow identification of immune signature of resilience (Aim 3). Integration of genomic with clinical, cognitive and immune data will allow predictive modeling, and Big Data driven analysis will allow identification of resilience mechanisms. The candidate is a Child and Adolescent Psychiatrist physician scientist who is committed to translational research in youth at risk for psychiatric conditions. His overarching career goal is to develop methods for early identification of subclinical phenotypes before the onset of major psychiatric disorders (i.e. depression and suicide attempts) and, through neuroscience informed interventions, divert the developmental trajectory from that of risk to that of resilience. The career development plan capitalizes on a multidisciplinary mentorship team. It involves one-on one mentoring with the primary “clinical research” mentor as well as the genomic, biostatistical, neurocognitive and immune system expert co- mentors, integrated with hands on research supervision in data collection and statistical analysis, and didactic coursework and workshops. The program is tailored to meet research and training aims. The project will be conducted in the fostering environment of the Children’s Hospital of Philadelphia and the University of Pennsylvania, that will provide the academic mentorship and the required resources to execute the research and training aims, allowing the candidate to launch an independent research career.

项目概要/摘要 儿童和青少年在成长过程中经常面临巨大的发展压力（即创伤）。而对于 一些，这将发展轨迹转向精神和一般健康障碍，另一些则是 有弹性的。大多数发展精神病理学研究都集中在风险上，而人们对风险知之甚少。 赋予弹性的机制。目前的研究旨在识别生物（基因组、免疫）、 支撑青少年复原力的心理和认知机制（定义为情绪低落） 患有严重发育压力（即创伤和家庭压力）的青少年的焦虑和自杀结果 抑郁症病史）。阐明弹性机制具有巨大的临床意义，因为它将改善 对发生抑郁症和/或自杀行为的风险进行分层，并可以识别生物、心理 和认知目标，可以为未来预防性干预措施的发展提供信息，旨在促进 复原力，减少与童年逆境相关的心理和总体健康不良后果。这 研究利用了费城神经发育队列中青少年基因分型的大型数据集 （PNC），已对认知表现和精神病理学进行了全面的表型分析，并且 报告了严重的创伤暴露。拟议的研究将基因组和认知数据与 用于定义约 9500 名 PNC 青少年横断面分析中复原力的临床指标（目标 1）； 纳入了抑郁症和自杀措施的纵向数据，这些数据是从电子病历中提取的 大约 750 名 PNC 青年的子集（目标 2）；并依赖于前瞻性数据收集，包括免疫分析 选择 PNC 个体来识别复原力的免疫特征（目标 3）。整合 具有临床、认知和免疫数据的基因组将允许预测建模和大数据驱动的分析 将允许识别弹性机制。候选人是一名儿童和青少年精神科医生 致力于对有精神疾病风险的青少年进行转化研究的医师科学家。他的 总体职业目标是开发在亚临床表型出现之前早期识别的方法。 重大精神疾病（即抑郁症和自杀企图）的发作，并通过神经科学获悉 干预措施，将发展轨迹从风险轨迹转向复原力轨迹。职业发展 计划利用多学科指导团队。它涉及与小学的一对一指导 “临床研究”导师以及基因组、生物统计学、神经认知和免疫系统专家共同 导师，结合数据收集和统计分析方面的实际研究监督以及教学 课程作业和研讨会。该计划专为满足研究和培训目标而定制。该项目将是 在费城儿童医院和费城大学的培育环境中进行 宾夕法尼亚州，将提供学术指导和执行研究所需的资源 和培训目标，让候选人能够开展独立的研究生涯。