Neural Mechanisms of Fear Extinction Across Anxiety Disorders

描述（由申请人提供）：焦虑症的特征在于夸大和持续的恐惧反应，并且先前已被表征为在许多脑区域中显示功能障碍。这些大脑区域包括杏仁核、腹内侧前额叶皮质、背侧前扣带回和海马体。重要的是，这些大脑区域参与了恐惧学习、恐惧的表达以及随后的消失。这种恐惧消退网络的功能在创伤后应激障碍的从头恐惧消退的背景下受损。这种恐惧消退网络的功能是否在其他焦虑中也受损 精神障碍如果是的话，所有障碍的功能障碍是否等同，或者在恐惧消退的背景下是否有一种独特的功能障碍模式，可以帮助区分其他障碍？本申请中提出的研究将采用最先进的神经成像工具、心理生理学工具和经过充分验证的两天恐惧条件反射和消退范例来开始回答上述问题。具体而言，诊断为社交焦虑障碍（SAD），广泛性焦虑障碍（GAD），特定恐惧症（SP）和惊恐障碍（PD）的患者将在3T fMRI扫描仪中接受恐惧条件反射和消退范式。先前从创伤后应激障碍（PTSD）、强迫症（OCD）和大型健康对照队列中获得的数据将用于在焦虑症之间进行比较，以编制大型数据矩阵。该矩阵将用于进行关联分析，以检查恐惧消退网络功能障碍之间的共性和差异。这些数据可能会导致更好地理解的精神病理学的焦虑症的背景下，一个单一的范例。

DESCRIPTION (provided by applicant): Anxiety disorders are characterized by exaggerated and perserverant fear responses and have been previously characterized to show functional impairment in a number of brain regions. These brain regions include the amygdala, ventromedial prefrontal cortex, dorsal anterior cingulate, and the hippocampus. Importantly, these brain regions are involved in fear learning, its expression, and its subsequent extinction. The function of this fear extinction network is impaired in PTSD within the context of de novo fear extinction. Is the function of this fear extinction network also impaired in the other anxiety disorders? If yes, is the functional impairment equivalent across all the disorders or is there a distinct pattern of dysfunction within the context of fear extinction that could help distinguish oe disorder from another? The research proposed in this application will employ state- of-the-art neuroimaging tools, psychophysiological tools, and a well-validated two- day fear conditioning and extinction paradigm to begin to answer the above stated questions. Specifically, patients diagnosed with social anxiety disorder (SAD), generalized anxiety disorders (GAD), specific phobia (SP), and panic disorder (PD) will undergo the fear conditioning and extinction paradigm while in a 3T fMRI scanner. Previously acquired data from posttraumatic stress disorder (PTSD), obsessive compulsive disorder (OCD), and a large cohort of healthy controls will be used to compare across the anxiety disorders to compile a large matrix of data. This matrix will be used to conduct a conjunction analysis to examine the commonalities and differences between disorders regarding the dysfunction of the fear extinction network. These data could lead to better understanding of the psychopathology of the anxiety disorders within the context of one single paradigm.