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: 8290799
• 负责人: CHARLES B NEMEROFF
• 金额: $ 40.17万
• 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/8290799
• 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. PUBLIC HEALTH RELEVANCE: Exposure to severe trauma is, unfortunately, extraordinarily common in the United States and worldwide, and consequently the prevalence rate of posttraumatic stress disorder (PTSD) is among the most common of the severe major psychiatric disorders. The fundamental unanswered question in the field is how to identify markers in trauma victims that predict who will later develop PTSD. The ability to identify those individuals with a high likelihood of developing PTSD will permit the development of a preventative intervention strategy that can be implemented appropriately and efficiently.

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）、人为灾难（漏油）、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，其患病率在美国和全世界可能会增加。尽管大多数创伤受害者都会经历重新体验、回避和过度警觉等主要症状，但对于大多数此类个体来说，这些症状不会变成慢性，也不会发展为创伤后应激障碍综合征。由于与这种疾病相关的医学和精神疾病发病率和死亡率非常高，因此识别出极少数极有可能患上创伤后应激障碍（PTSD）的创伤受害者非常重要。已有相当多的证据表明，遭受创伤后发生创伤后应激障碍的可能性是遗传和环境因素共同作用的结果。这个两个站点相连的 R-01 应用程序旨在利用基因组学、转录组学和表观遗传学方面的最先进进展，再加上全面的临床和心理测量，来解决 PTSD 临床服务和研究中这一尚未解答的重大问题。为了实现这一目标，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将招募500名遭受创伤的受试者，并定期进行为期一年的随访。这项重点突出、假设驱动的研究将仔细审查之前 确定心理和生物危险因素。遗传风险因素包括 ADCYAP1R1、FKBP5、DAT、BDNF、COMT、CRFR1、5HTTLPR、RGS2、GABA2 和 5HT3R 基因的多态性、新的遗传和表观遗传风险因素，最重要的是，通过使用传统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影响。这些发现应该提供方法来识别可能会患上创伤后应激障碍（PTSD）的创伤幸存者，因此可以转诊接受适当的心理治疗和/或精神药物治疗。这样的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 对我们医疗保健系统的负担。 公共卫生相关性：不幸的是，遭受严重创伤在美国和世界范围内非常普遍，因此创伤后应激障碍（PTSD）的患病率是最常见的严重主要精神疾病之一。该领域尚未解答的基本问题是如何识别创伤受害者的标记物，以预测谁以后会患上创伤后应激障碍（PTSD）。识别那些极有可能患上创伤后应激障碍（PTSD）的人的能力将允许制定可以适当和有效实施的预防性干预策略。