PTSD and Drug Dependence: Neuroimaging of Reward Circui*

创伤后应激障碍（PTSD）和药物依赖：奖励循环的神经影像*

• 批准号: 6896439
• 负责人: IGOR ELMAN
• 金额: $ 38.67万
• 依托单位: MCLEAN HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-06-01 至 2008-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6896439
• 关键词: behavior test; behavioral /social science research tag; clinical research; cocaine; cognition; comorbidity; euphoria; functional magnetic resonance imaging; human subject; interview; morphine; neuroanatomy; nucleus accumbens; patient oriented research; posttraumatic stress disorder; psychological stressor; psychopharmacology; reinforcer; substance abuse related disorder

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.

描述(由申请人提供)： 这项题为“创伤后应激障碍与药物依赖：奖赏回路的神经成像”的提案是对NIDA关于R01应用的请求的回应(#DA-04-001；压力和药物滥用：流行病学、病因学、预防和治疗)。这项建议的主要目的是研究脑奖励功能作为创伤后应激障碍(PTSD)物质使用障碍(SUDS)共病的潜在神经病理学基础。基本的神经科学和临床研究结果表明，慢性应激暴露会改变大脑奖赏回路，这种改变可能对促进肥皂水很重要。我们假设：1)功能受损的大脑奖赏机制可能包括一种神经底物，其潜在的核心创伤后应激障碍症状是对自然奖赏刺激或情绪麻木的反应性降低，2)这一神经底物因并存肥皂水的存在而进一步改变。这项拟议的项目旨在测试这些假说，整合了功能磁共振成像、精神药理学和认知心理学，以经验地测量创伤后应激障碍、可卡因依赖、创伤后应激障碍合并可卡因依赖和健康的奖赏反应。拟议的实验已经在不同的健康志愿者队列中成功进行，并在有和没有可卡因依赖的创伤后应激障碍受试者中试行。已发表的数据和初步结果表明，伏隔核(NAC)和相关结构在奖赏加工过程中的独特血流动力学反应模式，以及在奖赏功能的行为探测器上与创伤后应激障碍相关的表现异常。在这个项目中使用的三种不同的实验范式包括：a)低剂量的FDA批准的促快感药物吗啡，它可以安全地用于药物幼稚的受试者，b)以视觉处理诱人面孔的形式的社会奖励，以及c)在赌博任务中加入金钱激励刺激。我们预计会发现，在PTSD患者中，NAC对三种奖励刺激的激活幅度将比健康对照组小，但比患有PTSD和可卡因依赖的人大。这项研究计划将为理解和预防慢性应激暴露或创伤后应激障碍中的肥胖症的发展提供重要的线索。此外，我们的项目可能为情绪麻木症状的发病机制提供见解，这些症状不仅会导致创伤后应激障碍患者严重残疾，而且还会导致患有其他神经精神疾病的人，如肥胖症、精神分裂症和严重抑郁症。