Benzodiazepine Receptor in PTSD

描述（由申请人提供）：作为伊拉克自由行动（OIF）的一部分，目前有超过15万名士兵部署在伊拉克，12%的OIF士兵回国后患有创伤后应激障碍（PTSD）。389,100名士兵在越南战争中患上了慢性创伤后应激障碍，需要终生的精神卫生保健，工作效率下降，卫生保健资源的利用率更高。我们小组和其他人的研究表明，包括海马体、内侧前额皮质和杏仁核在内的功能回路发生了变化。然而，这些研究使用了大脑功能和结构的整体测量；对于大脑中介导PTSD症状的特定神经化学系统知之甚少。苯二氮卓类药物系统对大脑功能有抑制作用。动物研究表明，压力导致海马和内侧前额皮质苯二氮卓受体结合减少。据我们所知，在唯一一项已发表的PTSD神经受体研究中，我们通过单光子发射计算机断层扫描（SPECT）发现患有慢性战斗相关PTSD的退伍军人内侧前额叶皮层中苯二氮卓类受体结合减少。我们现在有了更高分辨率的成像（2毫米与SPECT的13毫米相比），NCRR为PI提供了高分辨率研究层析成像仪（HRRT）的资助，该项目已经实施了两年。我们使用PET HRRT和[C-11]氟马西尼扫描了几个患者，氟马西尼是一种与苯二氮卓受体结合的神经受体化合物，可用于成像苯二氮卓受体在活人大脑中的结合。创伤后应激障碍的神经生物学研究主要在长期和慢性创伤后应激障碍患者中进行。目前的共识是，PTSD的早期阶段不同于慢性和长期的PTSD，在疾病变成慢性和持续的之前进行早期干预可能会提供更好的治疗机会。PI在亚特兰大退伍军人事务部的伊拉克自由行动（OIF）创伤项目中工作，每个月有超过1000名士兵返回乔治亚州，因此有充足的招募资源用于早期创伤后应激障碍的研究。本研究是一项测量有创伤后应激障碍（PTSD）和无创伤后应激障碍（PTSD）的OIF退伍军人和非战斗暴露的退伍军人苯二氮卓受体结合情况的初步研究，比较有创伤后应激障碍（PTSD）和无创伤后应激障碍（PTSD）的OIF退伍军人和非战斗暴露的受试者使用PET HRRT [C-11]氟马西尼。我们假设与其他两组相比，PTSD患者前额皮质苯二氮卓受体结合减少。我们还将评估苯二氮卓结合预测长期预后的能力。我们预测，在评估后一年，前额叶结合减少将与慢性PTSD的进展有关。次要目的是评估PTSD症状与苯二氮卓类药物在前额皮质的结合之间的关系。本项目旨在检查患有创伤后应激障碍（PTSD）的伊拉克战争退伍军人体内苯二氮卓受体的结合情况，并看看这种方法是否可以用来预测哪些退伍军人会发展成慢性PTSD。苯二氮平系统在焦虑的调节中起着重要的作用。了解苯二氮卓类药物系统的变化可能会为患有创伤后应激障碍的伊拉克战争退伍军人带来新的治疗方法；该项目还提出了一种测试脑成像是否可以用于预测结果的新方法，这可能为识别需要早期干预的退伍军人提供重要工具。

DESCRIPTION (provided by applicant): Over 150,000 soldiers are currently deployed in Iraq as part of Operation Iraqi Freedom (OIF), and 12% of returning OIF soldiers have posttraumatic stress disorder (PTSD). 389,100 soldiers developed chronic PTSD from the Vietnam War, requiring a life-time of mental health care, with a loss of work productivity and greater utilization of health care resources. Research from our group and others showed changes in a functional circuit including hippocampus, medial prefrontal cortex, and amygdala. However these studies used global measures of brain function and structure; little is known about specific neurochemical systems in the brain that mediate PTSD symptoms. The benzodiazepine system mediates an inhibitory effect on brain function. Studies in animals show that stress results in a decrease in benzodiazepine receptor binding in the hippocampus and medial prefrontal cortex. In the only published neuroreceptor study in PTSD to our knowledge we showed a decrease in benzodiazepine receptor binding in medial prefrontal cortex with single photon emission computed tomography (SPECT) in veterans with chronic combat-related PTSD. We now have much higher resolution imaging (2 mm versus 13 mm with SPECT) with a grant funded by the NCRR to the PI for a High Resolution Research Tomograph (HRRT), which has been in place for two years. We have scanned several patients using PET HRRT and [C-11]flumazenil, a neuroreceptor compound that binds to the benzodiazepine receptor and can be used to image benzodiazepine receptor binding in the living human brain. Studies of the neurobiology of PTSD have been primarily performed in patients with long standing and chronic PTSD. There is currently a consensus that early phases of PTSD are different than chronic and long-standing PTSD, and that early interventions before the disorder becomes chronic and unremitting may offer a better opportunity for treatment. The PI is working in the Operation Iraqi Freedom (OIF) Trauma Program at the Atlanta VA, and there over 1000 soldiers returning to the state of Georgia each month, so there are ample sources of recruitment for research on early PTSD. This is a pilot study to measure benzodiazepine receptor binding in returning OIF veterans with and without PTSD, and non combat exposed comparison subjects with PET HRRT [C-11]flumazenil in OIF combat veterans with and without PTSD and non-combat exposed subjects. We hypothesize decreased benzodiazepine receptor binding in the prefrontal cortex in PTSD compared to the other two groups. We will also assess the ability of benzodiazepine binding to predict long-term outcome. We predict decreased prefrontal binding will be associated with progression to chronic PTSD at one year post assessment. Secondary aims are to assess the relationship between PTSD symptoms and benzodiazepine binding in the prefrontal cortex. This project is designed to examine binding of the benzodiazepine receptor in Iraq combat veterans with posttraumatic stress disorder (PTSD) and to see if this measure can be used to predict which returning veterans will progress to the development of chronic PTSD. The benzodiazepine system plays an important role in the regulation of anxiety. Understanding changes in the benzodiazepine system may lead to new treatments for Iraq combat veterans with PTSD; this project also proposes a novel method of testing whether brain imaging can be used to predict outcomes, which could provide an important tool for identifying veterans in need of early intervention.