PTSD and Drug Dependence: Neuroimaging of Reward Circuitry

描述（由申请人提供）： 这份题为“PTSD和药物依赖：奖赏回路的神经成像”的提案是对NIDA请求R 01申请（#DA-04-001;压力和药物滥用：流行病学，病因学，预防和治疗）的回应。本研究的主要目的是探讨脑奖励功能作为创伤后应激障碍（PTSD）中物质使用障碍（SUDs）共病的潜在神经病理学基础。基础神经科学和临床研究结果表明，大脑奖励电路被改变的方式，可能是重要的促进SUD慢性应激暴露。我们假设：1）功能受损的大脑奖励机制可能包括对自然奖励刺激或情感麻木的反应性降低的核心PTSD症状的神经基质，2）该神经基质因共病SUD的存在而进一步改变。拟议的项目旨在测试这些假设整合功能磁共振成像，精神药理学和认知心理学，以经验性地测量奖励反应在创伤后应激障碍，可卡因依赖，创伤后应激障碍与共病可卡因依赖和健康。拟议的实验已经在健康志愿者的单独队列中成功进行，并在有和没有可卡因依赖的PTSD受试者中进行了试点。发表的数据和初步结果表明，独特的模式，血流动力学反应的核丘脑（NAc）和相关结构在奖励过程中，沿着PTSD相关异常的表现上的行为探针的奖励功能。在这个项目中使用的三个不同的实验范例包括：a）低剂量的FDA批准的欣快药物吗啡，其可以安全地施用给药物未接触过的受试者，B）以有吸引力的面孔的视觉处理的形式的社会奖励和c）并入赌博任务的金钱激励刺激。我们期望发现，在PTSD患者中，NAc对三种奖励刺激的激活幅度相对于健康对照组较小，但大于PTSD和可卡因依赖共病的个体。这项研究计划将为理解和预防慢性应激暴露或PTSD背景下SUD的发展提供重要线索。此外，我们的项目可能会提供有关情感麻木症状发病机制的见解，这些症状不仅会导致PTSD患者严重残疾，还会导致其他神经精神疾病，如SUDs，精神分裂症和重度抑郁症。

DESCRIPTION (provided by applicant): This proposal, entitled "PTSD and drug dependence: neuroimaging of reward circuitry" is a response to NIDA Request for R01 Applications (#DA-04-001; Stress and Drug Abuse: Epidemiology, Etiology, Prevention and Treatment). The primary goal of this proposal is to investigate brain reward function as a potential neuropathological basis for substance use disorders (SUDs) comorbidity in posttraumatic stress disorder (PTSD). Basic neuroscience and clinical findings suggest that brain reward circuitry is altered by chronic stress exposure in ways that may be important for facilitating SUDs. We hypothesize that: 1) functionally impaired brain reward mechanisms may comprise a neural substrate underlying core PTSD symptoms of reduced reactivity to natural rewarding stimuli or emotional numbing and that 2) this neural substrate is further altered by the presence of comorbid SUDs. The proposed project is designed to test these hypotheses integrating functional magnetic resonance imaging, psychopharmacology and cognitive psychology to empirically measure reward responses in PTSD, cocaine dependence, PTSD with comorbid cocaine dependence and in health. The proposed experiments have already been successfully performed in separate cohorts of healthy volunteers and piloted in PTSD subjects with and without cocaine dependence. The published data and preliminary results suggest unique patterns of hemodynamic responses in the nucleus accumbens (NAc) and related structures during reward processing along with PTSD-related abnormalities in performance on a behavioral probe of reward function. Three distinct experimental paradigms to be used in this project include a) low doses of an FDA-approved euphorigenic drug, morphine, which can be safely administered to drug-naive subjects, b) social reward in the form of visual processing of attractive faces and c) monetary incentive stimuli incorporated into a gambling task. We expect to find that in PTSD patients the magnitude of the NAc's activation in response to the three rewarding stimuli will be smaller relative to healthy controls, but larger than in individuals with comorbid PTSD and cocaine dependence. This research plan will provide important leads for understanding and preventing the development of SUDs in the context of chronic stress exposure or PTSD. Furthermore our project may offer insights on the pathogenesis of emotional numbing symptoms, which cause severe disability not only in PTSD patients, but also in those suffering from other neuropsychiatric conditions such as SUDs, schizophrenia and major depression.