Epigenetic Linkage Between PTSD and Respiratory Disease in WTC Responders

世贸中心急救人员中 PTSD 与呼吸系统疾病之间的表观遗传联系

• 批准号: 8472604
• 负责人: BENJAMIN J LUFT
• 金额: $ 49.99万
• 依托单位: STATE UNIVERSITY NEW YORK STONY BROOK
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-09-01 至 2014-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8472604
• 关键词: Epigenetic; Linkage; Between; PTSD; Respiratory

DESCRIPTION (provided by applicant): The September 11, 2001 terrorist attack on the World Trade Center (WTC) was an extraordinary environmental disaster containing an unprecedented combination of physical and emotional exposures to rescue and recovery workers. As a direct result, WTC disaster responders attending the WTC Health Programs (WTC-HP) exhibit persistent symptoms of post-traumatic stress disorder (PTSD) and respiratory illness linked to the severity of their exposures. Indeed, one-quarter of responders affected by these conditions suffer from both. Mental-physical comorbidity leads to increased disability and utilization of medical services. This proposal focuses on potential mechanisms underlying PTSD/respiratory comorbidity that may facilitate development of more effective, theory-driven interventions for these difficult to treat patients. The overall goal of this proposal is to explicate the mechanisms linking PTSD and lower respiratory symptoms (LRS) in WTC responders through an epigenetics approach. Given longitudinal findings from observational data on the pathway from WTC exposures to PTSD to respiratory illness and supportive biological data, ecogenomics is the logical next step for understanding immune dysregulation and thus increased persistence of symptoms over time. In the long-term, identification of biomarkers using the approach described in Uddin et al. may help to uncover new tools to genetically characterize different pathways to PTSD and respiratory illness in responders. The specific aims of study are: 1. to determine and compare the methylation pattern of the peripheral blood DNA of patients with WTC-PTSD, patients who never developed PTSD, and a non-traumatized healthy control group. We will also determine whether the methylation patterns observed in the WTC cohort are: comparable to findings from the Detroit-area community study (Uddin et al. 2010) similar for patients with chronic WTC-PTSD and those with PTSD in remission; and 2. To examine differences in methylation patterns among Long Island clinic responders with (a) comorbid WTC-PTSD and respiratory illness, (b) only respiratory illness, (c) only WTC-PTSD, and (d) neither respiratory illness nor WTC-PTSD. To accomplish these AIMS we will conduct whole-genome methylation assays on peripheral blood from these patients using the HumanMethylation450 BeadChip and Infinium assay and compare methylation patterns to identify biomarkers which differential the groups outlined in Aims 1 and 2. In addition, we will validate methylation differences in specific loci. PUBLIC HEALTH RELEVANCE: In sum, recent years have seen enormous progress in the field of ecogenomics. Although focused specifically on PTSD/respiratory comorbidity in the WTC-HP, ultimately, our novel approach aims to better understand how exposure to extreme events 'gets under the skin' and jointly shapes physical and mental health outcomes, and gives rise to comorbid conditions. The proposed study applies epigenetic principles to a population-based cohort, one of the largest to be investigated by these methods to date.

描述（由申请人提供）：2001年9月11日，对世界贸易中心（WTC）的恐怖袭击是一场非凡的环境灾难，其中包含了身体和情感上的前所未有的结合，以营救和恢复工作者。作为一个直接的结果，参加WTC健康计划（WTC-HP）的WTC灾难反应者表现出创伤后应激障碍（PTSD）的持续症状和与暴露严重程度有关的呼吸道疾病。确实，受这些条件影响的四分之一的响应者都遭受了两者的影响。心理合并症会导致医疗服务的残疾和利用增加。该提案的重点是PTSD/呼吸道合并症的潜在机制，这些机制可能有助于为这些难以治疗患者而开发更有效的，理论驱动的干预措施。该提案的总体目标是解释机制 通过表观遗传学方法将WTC反应者中的PTSD和下呼吸道症状（LRS）联系起来。从观察数据中，从WTC暴露于PTSD到呼吸系统疾病和支持性生物学数据的途径的纵向发现是理解免疫失调的逻辑下一步，因此随着时间的推移症状的持久性增加。长期，使用Uddin等人中描述的方法对生物标志物进行识别。可能有助于发现新工具以遗传来表征反应者中PTSD和呼吸道疾病的不同途径。研究的具体目的是：1。确定和比较WTC-PTSD患者的外周血DNA的甲基化模式，从未开发PTSD的患者以及未经创伤的健康对照组。我们还将确定在WTC队列中观察到的甲基化模式是否与底特律地区社区研究的发现相当（Uddin等人，2010年），对于慢性WTC-PTSD的患者和缓解PTSD的患者也相似；和2。检查长岛诊所反应者的甲基化模式差异（a）（a）（a）合并WTC-PTSD和呼吸道疾病，（b）仅呼吸道疾病，（c）仅WTC-PTSD，以及（d）呼吸疾病也不是WTC-PTSD。 为了实现这些目的，我们将使用人甲基化450珠奇普和无INFINIUM分析对这些患者的外周血进行全基因组甲基化测定，并比较甲基化模式，以鉴定目标1和2的生物标志物。此外，我们还将验证特定特定位置的甲基化差异。 公共卫生相关性：总而言之，近年来在生态学学领域取得了巨大进展。尽管专门针对WTC-HP中的PTSD/呼吸道合并症，但最终，我们的新方法旨在更好地了解暴露于极端事件的“皮肤下”，并共同塑造身心健康的成果，并引起综合条件。拟议的研究将表观遗传原理应用于基于人群的队列，这是迄今为止这些方法最大的研究之一。