Clinical and biologic health trajectories after early life adversity

早年逆境后的临床和生物学健康轨迹

• 批准号: 10615904
• 负责人: Barbara Hirschman Chaiyachati
• 金额: $ 18.24万
• 依托单位: CHILDREN'S HOSP OF PHILADELPHIA
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-07-01 至 2027-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10615904
• 关键词: Abate; Acceleration; Accounting; Address; Adolescence; Adult; Age; Aging; Attention; Award; Behavioral; Biological; Child; Child Abuse; Child Abuse and Neglect; Child Health; Child Welfare; Childhood; Clinical; Clinical Immunology; Complex; DNA Methylation; Data; Development; Diagnosis; Diagnostic; Dimensions; Dose; Emotional; Environment; Epigenetic Process; Funding; Future; Genes; Genetic; Genetic Predisposition to Disease; Genetic Risk; Genomic approach; Genomics; Goals; Grant; Gur; Health; IL6 gene; Immunology; Inflammation; Inflammatory; Intervention; K-Series Research Career Programs; Leadership; Measurable; Measures; Medical; Mental Health; Mentorship; Methylation; Modernization; Morbidity - disease rate; Neurology; Outcome; Paper; Pediatric Hospitals; Pediatric Research; Pediatrics; Pennsylvania; Phenotype; Philadelphia; Physicians; Policies; Population Heterogeneity; Positioning Attribute; Post-Traumatic Stress Disorders; Predisposition; Psyche structure; Psychiatry; Psychopathology; Radiology Specialty; Reporting; Research; Research Personnel; Risk; Role; Sampling; Scientist; Sex Differences; Sexual abuse; Stress; Stressful Event; Supervision; Testing; Training; Translational Research; Trauma; Universities; Work; Writing; biobank; career; childhood adversity; clinical care; cohort; comorbidity; cytokine; developmental psychology; early life adversity; epigenomics; experience; gene environment interaction; genomic data; improved; innovation; insight; longitudinal, prospective study; maltreatment; methylome; mortality; multimodality; neuropsychiatry; pediatric trauma; phenomics; physical abuse; physical conditioning; pleiotropism; polygenic risk score; professor; psychogenetics; sex; skills; systemic inflammatory response; training opportunity; translational genomics; trauma exposure; whole genome

Project Summary/Abstract This career development award details a 5-year training plan to facilitate the transition of Dr. Barbara H. Chaiyachati to an independent career as a physician-scientist studying predictors of mental and physical health of children after trauma with an objective to identify actionable targets of intervention. Experiences of child abuse and neglect place hundreds of thousands of children at risk for negative health outcomes every year in the U.S. Better understanding of proximate mental and physical health predictors after childhood traumatic stressful events (TSE), including predictive role of genetic susceptibility integrated with early biologic embedding by epigenetic age acceleration (EAA) and increased inflammation, may facilitate targeted interventions to ameliorate the spectrum of long-term health burdens. Thus, multimodal phenomic and genomic approaches are needed to elucidate the complex connections between maltreatment and health. The proposed project builds on the diverse clinical and research experiences of the candidate, with mentorship led by Dr. Raquel Gur, the Karl and Linda Rickels Professor of Psychiatry, Neurology and Radiology at the University of Pennsylvania and an expert in neurodevelopmental trajectories, and Dr. Hakon Hakonarson, Professor of Pediatrics at the Children’s Hospital of Philadelphia and an expert in translational genomics. A team of collaborators adds expertise in developmental psychology, basic and clinical immunology, psychiatric genetics, and behavioral epigenomics, with grounding in child abuse clinical care. The research leverages large, ancestry-diverse, adversity-exposed cohorts within established biorepositories to identify measurable, biologically-relevant health predictors after adversity in childhood. Dr. Chaiyachati will conduct phenomic (physical, mental health, systemic inflammation by cytokines) and genomic (whole genome and methylome) assessments. Specifically, Aim 1 is to determine the impact of TSEs and genetic stress sensitivity, as marked by genetic risk for PTSD, on mental and physical health in adolescence; Aim 2 will assess the impact of TSE on epigenetic aging per DNA methylation clocks; and Aim 3 will test for increased inflammation after experiences of maltreatment. Completion of the proposed studies will improve our understanding of mental and physical health trajectories after experiences of trauma. This proposal will also provide the candidate with experience studying phenomic and genomic data, writing grants and scientific papers, and allow her to gain skills requisite for supervision and leadership. Furthermore, this proposal will establish Dr. Chaiyachati’s intersectional research agenda and position her for independence as a physician-scientist.

项目总结/摘要 这个职业发展奖详细介绍了一个5年的培训计划，以促进博士芭芭拉H。 Chaiyachati作为一名研究心理和身体健康预测因素的物理学家， 目的是确定干预的可操作目标。儿童经历 虐待和忽视每年使数十万儿童面临负面健康后果的风险， 更好地了解儿童创伤后的精神和身体健康预测因素 应激事件（TSE），包括遗传易感性与早期生物学 通过表观遗传年龄加速（EAA）和炎症增加嵌入，可能有助于靶向 采取干预措施，减轻各种长期健康负担。因此，多模式表型和基因组 需要采取各种办法来阐明虐待与健康之间的复杂联系。拟议 该项目建立在候选人的多样化临床和研究经验的基础上，由Dr. 拉奎尔·古尔是密歇根大学的卡尔和琳达·里克尔精神病学、神经病学和放射学教授。 宾夕法尼亚州和神经发育轨迹的专家，和博士Hakon Hakonarson，教授 他是费城儿童医院的儿科医生和翻译基因组学专家。一队 合作者增加了发展心理学，基础和临床免疫学，精神遗传学， 和行为表观基因组学，以儿童虐待临床护理为基础。这项研究利用了大量， 在已建立的生物储存库中，祖先多样的，暴露于逆境的队列，以确定可测量的， 生物学相关的健康预测因子在童年逆境后。Chaiyachati博士将进行现象学 （身体、心理健康、细胞因子引起的全身炎症）和基因组（全基因组和甲基化组） 评估。具体而言，目标1是确定TSE和遗传应激敏感性的影响，如标记的 通过PTSD的遗传风险，对青少年的心理和身体健康;目标2将评估TSE的影响 根据DNA甲基化时钟的表观遗传衰老; Aim 3将测试在 虐待的经历。完成拟议的研究将提高我们对精神和 经历创伤后的身体健康轨迹。这一建议还将为候选人提供 经验研究表型和基因组数据，撰写赠款和科学论文，并让她获得 监督和领导所必需的技能。此外，该提案将建立Chaiyachati博士的 交叉研究议程，并定位她作为一个独立的物理学家，科学家。

项目成果

Association between Asthma and Suicidality in 9-12-Year-Old Youths.

• DOI: 10.3390/brainsci12121602
• 发表时间: 2022-11-23
• 期刊: BRAIN SCIENCES
• 影响因子: 3.3
• 作者: Hoffman, Kevin W.;Visoki, Elina;Argabright, Stirling T.;Schultz, Laura M.;Didomenico, Grace E.;Tran, Kate T.;Gordon, Joshua H.;Chaiyachati, Barbara H.;Moore, Tyler M.;Almasy, Laura;Barzilay, Ran
• 通讯作者: Barzilay, Ran

Child Welfare System-Level Factors Associated with All-Cause Mortality Among Children in Foster Care in the United States, 2009-2018.

与美国寄养儿童全因死亡率相关的儿童福利系统层面的因素，2009-2018 年。

• DOI: 10.1177/10775595231177313
• 发表时间: 2023
• 期刊: Child maltreatment
• 影响因子: 5.1
• 作者: Lee,JoyceY;Steelesmith,DanielleL;Chaiyachati,BarbaraH;Kirsch,Jaclyn;Rao,Smitha;Fontanella,CynthiaA
• 通讯作者: Fontanella,CynthiaA