1 of 2 - Prospective Determination of Psychobiological Risk Factors for PTSD

1 of 2 - PTSD 心理生物学风险因素的前瞻性确定

• 批准号: 8470246
• 负责人: CHARLES B NEMEROFF
• 金额: $ 34.18万
• 依托单位: UNIVERSITY OF MIAMI SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-05-17 至 2017-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8470246
• 关键词: Accident and Emergency department; Accidents; Acute; Address; Adult; Algorithms; Alleles; Biological; Biological Factors; Biological Markers; Biological Models; Blood; Brain-Derived Neurotrophic Factor; Candidate Disease Gene; Cessation of life; Child Abuse; Chronic; Chronic Post Traumatic Stress Disorder; Classification; Clinical; Clinical Research; Clinical Services; Collection; Coupled; Crime; Cross-Sectional Studies; DNA; DNA Markers; Data; Data Collection; Data Set; Development; Diagnosis; Disasters; Disease; Dissociation; Doctor of Medicine; Doctor of Philosophy; Earthquakes; Enrollment; Environmental Risk Factor; Epidemiologic Studies; Epigenetic Process; Event; Exhibits; Exposure to; Family; Family Study; Female; Forcible intercourse; Gender; Gene Expression; Gene Expression Profile; Genes; Genetic; Genetic Polymorphism; Genetic Transcription; Genomics; Goals; HTR3A gene; Healthcare Systems; Heritability; Hospitals; Hurricane; Image; Individual; Injury; Intervention; Life; Link; Maps; Measurement; Measures; Medical; Mental disorders; Methods; Methylation; Microarray Analysis; Minority; Modeling; Morbidity - disease rate; Natural Disasters; Oils; Outcome; Pathogenesis; Patients; Phenotype; Population; Post-Traumatic Stress Disorders; Prevalence; Prevention; Prospective Studies; RGS2 gene; RNA; Reading; Recruitment Activity; Research; Risk; Risk Factors; Running; Sampling; Seminal; Series; Severities; Site; Social support; Statistical Models; Survivors; Symptoms; Techniques; Terrorism; Trauma; Tsunami; Twin Studies; United States; Universities; Validation; Variant; Violence; War; abuse neglect; automobile accident; base; biosignature; cohort; combat; disorder risk; experience; follow-up; gene function; genetic analysis; genetic risk factor; genome wide association study; genome-wide; inclusion criteria; inner city; instrument; man; meetings; mortality; novel; predictive modeling; prospective; psychobiologic; psychologic; psychopharmacologic; psychosocial; research study; resilience; statistics; tool; transcriptomics; trauma centers

DESCRIPTION (provided by applicant): Post-traumatic Stress Disorder (PTSD) is one of the most highly prevalent psychiatric disorders and its prevalence is likely increasing in the United States and worldwide due to the rising numbers of natural disasters (earthquakes, hurricanes, tsunamis), man-made disasters (oil spills), terrorism and wars, as well as violent crime and automobile accidents. Although the majority of trauma victims experience the cardinal symptoms of re-experiencing, avoidance and hyperarousal, for the large majority of such individuals, these symptoms do not become chronic nor do they develop syndromal PTSD. It is important to identify the large minority of trauma victims with a high likelihood of developing PTSD because of the very significant medical and psychiatric morbidity and mortality associated with this disorder. There is already considerable evidence that the likelihood of developing PTSD after trauma exposure is due to a combination of genetic and environmental factors. This two-site, linked R-01 application seeks to utilize state-of-the art advances in genomics, transcriptomics and epigenetics, coupled with comprehensive clinical and psychological measures, to address this seminal unanswered question in PTSD clinical service and research. To achieve this goal, 500 trauma-exposed subjects will be recruited at the University of Miami Ryder Trauma Center and the Emory University affiliated Grady Memorial Hospital and followed at regular intervals for one year. This focused, hypothesis-driven study will scrutinize previously identified psychological and biological risk factors. Genetic risk factors include polymorphisms of the ADCYAP1R1, FKBP5, DAT, BDNF, COMT, CRFR1, 5HTTLPR, RGS2, GABA2 and 5HT3R genes, novel genetic and epigenetic risk factors and most importantly, the primary downstream effects of these genomic and epigenetic findings by the use of conventional and newer statistical modeling methods. These findings should provide the means to identify trauma survivors who will likely develop PTSD and can therefore be referred for appropriate psychotherapeutic and/or psychopharmacologic treatment. Such a strategy has the potential to help redefine psychobiological subtypes of PTSD as well as to reduce the burden of chronic PTSD on our healthcare system.

描述（由申请人提供）：创伤后应激障碍（PTSD）是最常见的精神疾病之一，由于自然灾害（地震，飓风，海啸），人为灾害（石油泄漏），恐怖主义和战争以及暴力犯罪和汽车事故的数量不断增加，其患病率可能在美国和世界范围内增加。虽然大多数创伤受害者经历的主要症状是重新体验，回避和过度觉醒，但对于大多数这样的人来说，这些症状不会变成慢性的，也不会发展成综合征性PTSD。重要的是要确定大量的少数创伤受害者与发展PTSD的可能性很高，因为非常显着的医疗和精神疾病的发病率和死亡率与这种疾病。已经有相当多的证据表明，创伤暴露后发展为PTSD的可能性是由于遗传和环境因素的结合。这两个网站，链接的R-01应用程序旨在利用最先进的基因组学，转录组学和表观遗传学的进步，再加上全面的临床和心理措施，以解决这个开创性的创伤后应激障碍临床服务和研究悬而未决的问题。为了实现这一目标，将在迈阿密大学莱德创伤中心和埃默里大学附属格雷迪纪念医院招募500名创伤暴露受试者，并定期随访一年。这项重点突出的假设驱动的研究将仔细审查以前 确定心理和生物风险因素。遗传风险因素包括ADCYAP 1 R1、FKBP 5、DAT、BDNF、COMT、CRFR 1、5 HTTLPR、RGS 2、GABA 2和5 HT 3R基因的多态性，新的遗传和表观遗传风险因素，最重要的是，通过使用常规和更新的统计建模方法，这些基因组和表观遗传发现的主要下游效应。这些发现应该提供一种方法，以确定创伤幸存者谁可能会发展PTSD，因此可以参考适当的心理治疗和/或精神药理学治疗。这种策略有可能帮助重新定义PTSD的心理生物学亚型，并减轻慢性PTSD对我们医疗系统的负担。