TWIN STUDY OF BIOLOGIC MARKERS FOR PTSD

PTSD 生物标志物的双胞胎研究

• 批准号: 2416118
• 负责人: ROGER K. PITMAN
• 金额: $ 57.52万
• 依托单位: HARVARD MEDICAL SCHOOL
• 依托单位国家: 美国
• 财政年份: 1995
• 资助国家: 美国
• 起止时间: 1995-09-30 至 1999-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2416118
• 关键词: auditory discrimination; auditory stimulus; behavioral /social science research tag; behavioral habituation /sensitization; biomarker; dexamethasone suppression test; disease /disorder proneness /risk; dizygotic twins; environmental stressor; evoked potentials; family genetics; genetic registry /resource /referral center; human subject; mental disorder diagnosis; monozygotic twins; patient /disease registry; posttraumatic stress disorder; psychophysiology; startle reaction; stimulus /response; veterans; war /peace

DESCRIPTION (Adapted from applicant's abstract): This project will take advantage of the unique opportunity presented by the Vietnam Era Twin (VET) Registry to evaluate potential biologic markers for familial vulnerability to the development of PTSD. Subjects will include twins discordant for combat exposure. Several know biologic PTSD markers will be evaluated by comparing their presence in the (high-risk) unexposed monozygotic (Mz) co-twins of exposed twins with combat-related PTSd versus the (low-risk) unexposed Mz co- twins of exposed twins without combat-related PTSD. A limited sample of (medium-high-risk) unexposed dizygotic (Dz) co-twins of exposed twins with combat-related PTSD will be recruited in order to test whether any identified familial biologic vulnerability factor for PTSD represents the produce of heredity. An additional aim is to examine susceptibility to mental disorder as a familial, possibly inherited, vulnerability factor for PTSD by performing comprehensive psychodiagnostic interviews on subjects in an design parallel to that employed for the PTSD biologic markers. Another aim is to evaluate potential acquired biologic PTSD signs by comparing exposed PTSD twins versus their unexposed Mz co-twins. Dependent variables will include (a) autonomic and muscular startle responses and their habituation; (b) amplitude of the P3 event-related potential (ERP) component in a target discrimination task; (c) slope of the P2 ERP component as a function f tone intensity in a stimulus intensity modulation experiment; and (d) suppression of salivary cortisol following low-dose oral dexamethasone. Each marker to be studied is non-invasive; can be measured on an ambulatory basis; has been shown in previous, published, peer-reviewed research to significantly differentiate PTSD and non-PTSD subject groups; and is capable of being informed by the data to be obtained in the proposed project. Subjects will be diagnosed by a field psychologist using the Clinician- Administered PTSD Scale, Structured Clinical Interview for DSM-IV, and other instruments. Dependent variables will be measured at a traveling field psychophysiology laboratory set up at a VA Medical Center or Vet Center near the subject's home. Statistical significance will be tested by means of univariate and multivariate analyses of variance and covariance and independent t-tests performed on key groups, and selected subgroups. Results are expected to advance our understanding of the constitutional versus acquired nature of biologic abnormalities in PTSD and the pathogenesis of this disorder. Results will also have implications for the prophylactic screening of persons at high risk for the development of PTSD upon exposure to military combat or other severe stressors.

描述（改编自申请人的摘要）：该项目将采取 利用越南时代双胞胎提供的独特机会 (VET) 评估家族潜在生物标志物的登记处 易受创伤后应激障碍 (PTSD) 发展的影响。受试者将包括双胞胎 与战斗暴露不一致。一些人知道生物 PTSD 标记会 通过比较它们在（高风险）未暴露环境中的存在来评估 患有与战斗相关的 PTSd 的暴露双胞胎的同卵 (Mz) 同卵双胞胎 与（低风险）未暴露的同卵双胞胎相比，未暴露的双胞胎 与战斗相关的创伤后应激障碍。未暴露的（中高风险）有限样本 患有与战斗相关的创伤后应激障碍 (PTSD) 的暴露双胞胎的异卵 (Dz) 双胞胎将 被招募来测试是否有任何已识别的家族生物学 PTSD 的脆弱性因素代表遗传的产物。一个 另一个目的是检查对精神障碍的易感性 PTSD 的家族性、可能遗传性、脆弱性因素，通过执行 对设计中的受试者进行全面的心理诊断访谈 与用于 PTSD 生物标记的方法平行。另一个目标 是通过比较来评估潜在的获得性生物 PTSD 体征 暴露于 PTSD 的双胞胎与未暴露于 PTSD 的同卵双胞胎。 因变量将包括 (a) 自主神经和肌肉惊吓 反应及其习惯； (b) P3事件相关的幅度 目标辨别任务中的潜在（ERP）组成部分； (c) 斜率 P2 ERP 分量作为刺激中音调强度的函数 强度调制实验； (d) 抑制唾液分泌 小剂量口服地塞米松后皮质醇。每个标记应 研究是非侵入性的；可以动态测量；有 之前已发表的同行评审研究表明 显着区分 PTSD 和非 PTSD 受试者组；并且是 能够通过拟议中获得的数据获悉 项目。 现场心理学家将使用临床医生对受试者进行诊断- 执行 PTSD 量表、DSM-IV 结构化临床访谈，以及 其他仪器。因变量将在行驶时测量 在退伍军人管理局医疗中心或兽医设立的现场心理生理学实验室 中心靠近对象的家。将检验统计显着性 通过单变量和多变量方差分析 对关键组进行协方差和独立 t 检验，并选择 亚组。结果预计将加深我们对 PTSD 中生物异常的先天性与后天性 以及这种疾病的发病机制。结果也会有 对高危人群预防性筛查的影响 经历军事战斗或其他严重的情况后出现创伤后应激障碍（PTSD） 压力源。