Twin Study of Biologic Markers for PTSD

描述（由申请人提供）：这一竞争性的延续建议将利用一个独特的机会，进一步跟进一系列调查的起源，生物标志物的创伤后应激障碍（PTSD）在人口的同卵双胞胎不和谐的战斗暴露在越南。要解决的主要可能的标记来源是：a.）PTSD与B.）获得性创伤后应激障碍将通过检查配对间诊断的主要影响（创伤后应激障碍与非创伤后应激障碍在战斗暴露的双胞胎中），以及通过对比（高风险）战斗暴露的双胞胎与创伤后应激障碍的双胞胎的（高风险）战斗-未暴露的双胞胎与（低风险）战斗暴露的双胞胎无创伤后应激障碍的双胞胎的（低风险）战斗-未暴露的双胞胎来评估家族脆弱性。通过检查诊断和配对内暴露（战斗与无战斗）之间的相互作用，以及通过对比PTSD战斗双胞胎与其自身的战斗-未暴露的双胞胎，评估获得性PTSD体征。最近的试点数据表明，以下可能是PTSD的家庭脆弱性因素：a）在fMRI期间被动观察明显恐惧的面部表情期间，减少喙前扣带皮层（rACC）和增加杏仁核激活，和B.）增加背侧ACC激活过程中的多源干扰任务（MSIT）在fMRI。相比之下，试点数据表明，C。心理生理条件性恐惧反应消退的保持受损可能是获得性PTSD的标志。这项相互竞争的延续建议的工作将包括在额外的双胞胎受试者中测试上述三项试点研究结果，以获得明确的结果。结果（c）也将使用fMRI进行追踪。其他实验将包括测量d。在正电子发射断层扫描期间的战斗和其他个人压力事件的脚本驱动的图像期间的局部脑血流，以及e.）通过磁共振波谱法测定dACC、rACC、腹内侧前额叶皮质和海马中的N-乙酰天冬氨酸水平。将邀请双胞胎受试者前往马萨诸塞州总医院进行为期两天的神经成像方案。这些结果有望促进我们对创伤后应激障碍生物学异常的先天性与后天性以及这种疾病的神经解剖学和发病机制的理解。此外，拟议的研究可能会确定候选基因对PTSD风险影响的生物介质。公共卫生相关性：这项研究将试图进一步解决创伤后应激障碍（PTSD）的生物异常的起源，通过确定它们是否存在于患有PTSD的战斗退伍军人的同卵双胞胎中。发现获得的异常可能成为PTSD治疗的目标，而作为PTSD风险因素的异常可用于筛查风险人群和可能的预防干预措施。

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.