Twin Study of Biologic Markers for PTSD

描述(由申请人提供)：这项竞争性的延续提案将利用一个独特的机会，进一步跟进越南一群不适合战斗暴露的同卵双胞胎中创伤后应激障碍(PTSD)生物标志物来源的一系列调查。要解决的主要可能的标记来源是：a)创伤后应激障碍家族易感性与b.)后天创伤后应激障碍征。将通过检查双胞胎之间诊断的主要效果(在战斗暴露的双胞胎中PTSD与非PTSD)，以及通过对比战斗暴露的双胞胎中患有PTSD的(高风险)战斗暴露的同卵双胞胎与没有战斗暴露的双胞胎的(低风险)战斗暴露的同卵双胞胎来评估家庭脆弱性。获得性创伤后应激障碍征兆将通过检查诊断和内部暴露(战斗与非战斗)之间的相互作用，以及通过对比创伤后应激障碍战斗双胞胎和他们自己的战斗未暴露的同卵双胞胎来评估。最近的试点数据表明，以下可能是创伤后应激障碍的家族性易感因素：a.在fMRI中被动观看公开的恐惧面部表情时，嘴前扣带回皮质(RACC)减少和杏仁核激活增加，以及b.)在fMRI的多源干扰任务(MSIT)中，背侧ACC的激活增加。相比之下，试点数据表明，c.)心理生理条件恐惧反应的消退能力减退可能是后天创伤后应激障碍的征兆。这项相互竞争的延续提案中的工作将包括在另外的双胞胎受试者中测试上述三个试点结果，以试图获得确定的结果。发现(C)也将使用功能磁共振成像进行。其他实验将包括测量d。)正电子发射断层扫描中脚本驱动的战斗图像和其他个人应激事件中的局部脑血流，以及e。)核磁共振波谱测定dACC、rACC、腹内侧额叶皮质和海马区N-乙酰天冬氨酸水平。双胞胎受试者将被邀请前往马萨诸塞州综合医院进行为期两天的神经成像方案。这一结果有望促进我们对创伤后应激障碍生物异常的体质性和获得性的理解，以及这种疾病的神经解剖学和发病机制。此外，这项拟议的研究可能会确定候选基因对创伤后应激障碍风险影响的生物中介。公共卫生相关性：这项研究将试图通过确定创伤后应激障碍(PTSD)退伍军人的同卵双胞胎中是否存在生物异常来进一步解决创伤后应激障碍(PTSD)的生物异常。已发现的异常可成为创伤后应激障碍治疗的目标，而作为创伤后应激障碍风险因素的异常可用于筛查有风险的人和可能的预防性干预措施。

DESCRIPTION (provided by applicant): This competing continuation proposal will take advantage of a unique opportunity to further follow up on a series of investigations of the origin of biologic markers for post-traumatic stress disorder (PTSD) in a population of identical twins discordant for combat exposure in Vietnam. The main possible marker origins to be addressed are: a.) familial vulnerability for PTSD vs. b.) acquired PTSD sign. Familial vulnerability will be evaluated by examining the main effect of between-pair Diagnosis (PTSD vs. non- PTSD in the combat-exposed twin), as well as by contrasting the (high-risk) combat-unexposed co-twins of combat-exposed twins with PTSD vs. the (low-risk) combat-unexposed co-twins of combat-exposed twins without PTSD. Acquired PTSD sign will be evaluated by examining the interaction between Diagnosis and within-pair Exposure (combat vs. no combat), as well as by contrasting the PTSD combat twins vs. their own combat-unexposed co-twins. Recent pilot data suggest that the following may be familial vulnerability factors for PTSD: a.) decreased rostral anterior cingulate cortex (rACC) and increased amygdala activation during passive viewing of overt fearful facial expressions during fMRI, and b.) increased dorsal ACC activation during a multi-source interference task (MSIT) during fMRI. In contrast, pilot data suggest that c.) impaired retention of extinction of a psychophysiologic conditioned fear response may be an acquired PTSD sign. The work in this competing continuation proposal will include testing the above three pilot findings in additional twin subjects in an attempt to obtain definitive results. Finding (c) will also be pursued using fMRI. Additional experiments will include measuring d.) regional cerebral blood flow during script-driven imagery of combat and other personal stressful events during positron emission tomography, and e.) n- acetyl aspartate levels in dACC, rACC, ventromedial prefrontal cortex, and hippocampus by magnetic resonance spectroscopy. Twin subjects will be invited travel to the Massachusetts General Hospital for two days of neuroimaging protocols. Results are expected to advance our understanding of the constitutional vs. acquired nature of biologic abnormalities in PTSD and the neuroanatomy and pathogenesis of this disorder. Additionally the proposed research may identify biologic mediators of the effects of candidate genes on risk for PTSD. PUBLIC HEALTH RELEVANCE: This study will attempt to further resolve the origin of biologic abnormalities in post-traumatic stress disorder (PTSD) by determining whether or not they are present in the identical twins of combat veterans with PTSD. Abnormalities that are found to be acquired could become the target of PTSD treatments, whereas abnormalities that serve as risk factors for PTSD could be used in screening for persons at risk and possible preventive interventions.