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

基本信息

批准号：
10427848
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
项目类别：
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/10427848
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 Clinical Research Complex DNA Methylation Data Development Diagnosis 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 Longitudinal Studies 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 maltreatment methylome mortality multimodality neuropsychiatry pediatric trauma phenomics physical abuse physical conditioning pleiotropism polygenic risk score professor prospective psychogenetics sex skills systemic inflammatory response training opportunity translational genomics trauma exposure whole genome

项目摘要

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.

项目摘要/摘要该职业发展奖详细介绍了一项为期5年的培训计划，以促进Barbara H.博士的过渡。 Chaiyachati从事独立职业，作为身体健康的身体健康的预测指标创伤后的儿童，目的是确定可行的干预目标。孩子的经历虐待和忽视，每年有成千上万的儿童处于负面健康状况的风险美国对儿童创伤后的近端身心健康预测因素更好地理解压力事件（TSE），包括与早期生物学结合的遗传易感性的预测作用通过表观遗传年龄加速（EAA）嵌入并增加感染，可能有助于靶向改善长期健康伯良的干预措施。那是多模式现象和基因组需要采取方法来阐明虐待与健康之间的复杂联系。提议项目基于候选人的潜水员临床和研究经验，并由博士博士领导。拉奎尔·古尔（Raquel Gur），卡尔（Karl）和琳达·里克尔斯（Linda Rickels）的精神病学教授，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，以及Hakon Hakonarson博士费城儿童医院的儿科和翻译基因组学专家。一个团队合作者在发展心理学，基础和临床免疫学，精神遗传学方面增加了专家，和行为表观基因组学，在虐待儿童的临床护理中基础。该研究利用了很大的祖先多样，既定的生物座席店内都暴露于广告的人群，以识别可衡量的，可衡量的，童年广告后，与生物学相关的健康预测因素。 Chaiyachati博士将进行现象（物理，心理健康，细胞因子的全身感染）和基因组（全基因组和甲基组）评估。具体而言，目标1是确定TSE和遗传应力敏感性的影响，如标记通过PTSD的遗传风险，青少年的心理和身体健康； AIM 2将评估TSE的影响关于每个DNA甲基化时钟的表观遗传衰老； AIM 3将测试注射的增加虐待的经历。拟议研究的完成将提高我们对心理和经历创伤经历的身体健康轨迹。该建议还将为候选人提供研究现象和基因组数据，撰写赠款和科学论文的经验，并允许她获得需要进行监督和领导的技能。此外，该提议将建立Chaiyachati博士交叉研究议程并将其定位为独立性作为身体科学家。