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。

基本信息

批准号：
10448271
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
项目类别：
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/10448271
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 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 Psyche structure Psychiatrist Psychopathology Reporting Research Research Training Resistance Resources Risk Risk Estimate Risk Factors 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 large datasets machine learning algorithm multidisciplinary polygenic risk score predictive modeling prevent preventive intervention programs prospective psychologic research clinical testing resilience risk stratification screening sex stress related disorder suicidal suicidal behavior trauma exposure traumatic stress

项目摘要

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）。一些，这将发展轨迹转向精神和一般健康障碍，另一些则是大多数关于发展精神病理学的研究都集中在风险上，而对风险的了解却很少。当前的研究旨在确定生物（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阐明抑郁症的恢复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。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，并且拟议的研究将基因组和认知数据与大量报告的创伤暴露相结合。用于定义约 9500 名 PNC 青少年横断面分析中复原力的临床测量（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约 750 名 PNC 青少年的子集（目标 2）；并依赖于前瞻性数据收集，其中包括免疫分析选择 PNC 个体以识别复原力的免疫特征（目标 3）。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复原机制。候选人是儿童和青少年精神病学家。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。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。计划利用了多学科的指导团队，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该计划是为满足研究和培训目标而定制的。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。

项目成果

期刊论文数量（14）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Association among income loss, financial strain and depressive symptoms during COVID-19: Evidence from two longitudinal studies.

DOI：
10.1101/2020.09.15.20195339
发表时间：
2021-08-01
期刊：
Journal of affective disorders
影响因子：
6.6
作者：
Hertz-Palmor, Nimrod;Moore, Tyler M;Barzilay, Ran
通讯作者：
Barzilay, Ran

Allostatic load in early adolescence: gene / environment contributions and relevance for mental health.

青春期早期的稳态负荷：基因/环境的贡献以及与心理健康的相关性。

DOI：
10.1101/2023.10.27.23297674
发表时间：
2023
期刊：
medRxiv : the preprint server for health sciences
影响因子：
0
作者：
Hoffman,KevinW;Tran,KateT;Moore,TylerM;Gataviņš,MārtiņšM;Visoki,Elina;DiDomenico,GraceE;Schultz,LauraM;Almasy,Laura;Hayes,MatthewR;Daskalakis,NikolaosP;Barzilay,Ran
通讯作者：
Barzilay,Ran

Making Evidence-Based Knowledge Accessible to Parents to Promote Child Mental Health Care.

DOI：
10.1016/j.jaac.2022.03.005
发表时间：
2022-12
期刊：
JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY
影响因子：
13.3
作者：
Shoval, Gal;Chiu, Jamie C.;Taylor, Jerome H.;Barzilay, Ran
通讯作者：
Barzilay, Ran

Need for Ethnic and Population Diversity in Psychosis Research.

DOI：
10.1093/schbul/sbab048
发表时间：
2021-07-08
期刊：
Schizophrenia bulletin
影响因子：
6.6
作者：
Burkhard C;Cicek S;Barzilay R;Radhakrishnan R;Guloksuz S
通讯作者：
Guloksuz S

Phenotypic Characterization of Youth Admitted To Acute Psychiatric Inpatient Unit Following Self-Harm Behavior.

DOI：
10.1080/13811118.2020.1865223
发表时间：
2022-07
期刊：
ARCHIVES OF SUICIDE RESEARCH
影响因子：
2.8
作者：
Schwartz-Lifshitz, Maya;Ben-Dor, David H.;Bustan, Yael;Zalsman, Gil;Gothelf, Doron;Weizman, Abraham;Barzilay, Ran
通讯作者：
Barzilay, Ran