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: 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
• 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

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.

项目总结/摘要 儿童和青少年往往在面临巨大的发展压力（即创伤）的情况下成长。而对于 有些人，这将发展轨迹转移到精神和一般健康障碍，其他人则 有弹性大多数关于发展性精神病理学的研究都集中在风险上，而对发展性精神病理学的研究却知之甚少。 赋予弹性的机制。目前的研究旨在确定生物（基因组，免疫）， 心理和认知机制，支持青年的弹性，定义为具有低情绪， 焦虑和自杀的结果，在青年与大量的发展压力暴露（即创伤和家庭 抑郁症史）。阐明弹性机制具有巨大的临床意义，因为它将改善 发展抑郁症和/或自杀行为的风险分层，并可识别生物学、心理学和行为学特征。 和认知目标，可以为未来的预防性干预措施的制定提供信息， 复原力，减少与童年逆境相关的心理和一般健康不良后果。的 一项研究利用了费城神经发育队列的基因型青年的大数据集 (PNC)，已经对认知表现和精神病理学进行了全面的表型分析， 报告了严重的外伤拟议的研究将基因组和认知数据与 在对约9500名PNC青年进行的横断面分析中，用于定义复原力的临床指标（目标1）; 合并了抑郁和自杀措施的纵向数据，从电子病历中提取， 约750名PNC青少年的子集（目标2）;并依赖于前瞻性数据收集，包括 选择PNC个体，以允许识别恢复力的免疫特征（Aim 3）。一体化 基因组与临床，认知和免疫数据将允许预测建模和大数据驱动的分析 将有助于确定复原机制。候选人是儿童和青少年精神病学家 医生科学家，致力于在有精神病风险的青年中进行转化研究。他 总体职业目标是开发方法，用于在临床前早期识别亚临床表型。 严重精神疾病（即抑郁症和自杀企图）的发作，并通过神经科学告知 通过采取干预措施，将发展轨迹从风险转向复原力。职业发展 该计划利用了一个多学科的辅导团队。它涉及与主要客户进行一对一的指导， “临床研究”导师以及基因组学、生物统计学、神经认知和免疫系统专家共同 导师，在数据收集和统计分析方面与研究监督相结合， 课程和研讨会。该计划是量身定制，以满足研究和培训目标。该项目将 在费城儿童医院和费城大学的寄养环境中进行 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，让候选人开始独立的研究生涯。

项目成果

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
• 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

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

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

Association between neutrophil to lymphocyte ratio and mood polarity in adolescents admitted to an inpatient psychiatric ward.

• DOI: 10.1097/yic.0000000000000412
• 发表时间: 2022-11-01
• 期刊: International clinical psychopharmacology
• 影响因子: 2.6