Kappa Opioid Receptor Imaging in PTSD

描述(由申请人提供)：该项目旨在提供一个对与创伤相关的主要应激源的适应和适应不良反应的翻译模型，不仅有可能为创伤后应激障碍的病因提供新的见解，而且还可以指导创伤后应激障碍患者的新治疗发展。我们的建议旨在对两个主要的应激反应系统--kappa阿片受体系统和糖皮质激素系统的功能提供一个综合的观点，为未来对这些系统测试针对这些患者的特定干预措施的研究奠定基础。这是一项为期3年的研究，涉及三个研究组[创伤后应激障碍(PTSD)，n=10；创伤暴露健康对照组(TC)，n=10；非创伤暴露健康对照组(HC，n=10；年龄范围18-50岁，每个队列中男女人数相等])的30名药物初学者，他们将通过公开广告招募，并被邀请参加使用[11C]LY2795050和PET对kappa阿片受体进行的医学和精神病学评估、神经内分泌评估、一项MRI研究和一项PET研究。 公共卫生相关性：该提案旨在确定kappa阿片受体(k-OR)在创伤后应激障碍的病理生理学中的潜在作用。我们建议招募创伤后应激障碍患者以及有和没有创伤暴露的健康对照组受试者，并将使用新型选择性k-OR放射性配基[11C]LY2795050和正电子发射断层扫描(PET)在体内研究k-OR。这项研究将首次确定这种阿片受体亚型在创伤后应激障碍中的作用，并可能为这一患者群体的新治疗开发奠定基础。

DESCRIPTION (provided by applicant): This project aims to provide a translational model of adaptive and maladaptive responses to major stressors associated with trauma with the potential to not only provide novel insight into the etiology of PTSD but in addition to guide nove treatment developments for patients with PTSD. Our proposal aims to provide an integrative view on the functions of two major stress-response systems, the kappa opioid receptor system and glucocorticoids, which lays the foundation for future studies of these systems testing specific interventions for these patients. This proposal is a 3-year study involving thirty drug-naive participants in three study groups [PTSD, n=10; trauma-exposed healthy control subjects (TC), n=10; non trauma-exposed healthy control subjects (HC), n=10; age range 18-50 years, equal numbers of men and women in each cohort] who are to be recruited through public advertisement and invited to participate in a medical and psychiatric evaluation, neuroendocrine assessments, one MRI study and one PET study of kappa opioidreceptors using [11C]LY2795050 and PET. PUBLIC HEALTH RELEVANCE: This proposal aims to determine the potential role of kappa opioid receptors (k-OR) in the pathophysiology of PTSD. We propose to recruit patients with PTSD, as well as healthy control subjects with and without trauma exposure and will study k-ORs in vivo using the novel selective k-OR radioligand [11C]LY2795050 and positron emission tomography (PET). This study will for the first time determine the role of this opoid receptor subtype in PTSD and may lay the foundation for novel treatment developments for this patient population.