Distinct & Common Neural Correlates of Fear Disorders, OCD, & Eating Disorders

描述(申请人提供)：精神疾病可以被可靠地诊断，但大脑功能障碍如何导致临床症状尚不清楚。正如NIMH战略计划所确认的那样，迫切需要研究诊断过程中的多个潜在大脑回路，以确定患有共同神经功能障碍的患者组。这种方法的最终目的是利用脑功能障碍作为临床诊断的辅助手段，指导治疗方法的选择和发展。与这种方法一致，这个为期3年的R01应用程序建议使用经过充分验证的神经行为任务来检查三种精神障碍的多个大脑系统：社交焦虑症(SAD)、强迫症(OCD)和神经性厌食症(AN)。尽管在临床上不同，但这些障碍都有围绕非理性恐惧组织起来的适应不良行为的共同特征。此外，这些障碍之间的关系也引起了激烈的争论。每种障碍都与不同的大脑系统有关：SAD的皮质-杏仁核回路，强迫症的额纹状体-苍白球回路，以及AN的皮质-中脑边缘回路。研究团队有使用经过充分验证的神经行为任务来评估这些不同神经系统的功能以及招募和评估所有三种类型的患者所需的临床专业知识的经验。具体地说，这个项目将研究180名参与者(40名SAD，40名强迫症，40名AN和60名健康对照组[HC])，使用以下神经行为任务：1)恐惧消退保持作为一种“安全”学习的衡量标准(杏仁皮质功能的探针)；2)脉冲前抑制作为感觉运动门控的一种衡量标准(皮质-纹状体-苍白球功能的一种探针)；以及3)延迟折扣作为延迟满足感能力的一种衡量标准(皮质-中脑边缘功能的一种探针)。所有180名参与者将完成所有三项任务和详细的临床评估。这项工作将在三年内完成，从而能够快速评估这一方法的成功。目标是：1)如试点数据所示，确定每个障碍与其中一项任务中的特定异常有关；2)确定这些异常是特定的还是与其他障碍共享的；3)探索反应模式是否与维度特征、临床特征或跨障碍的新病例分组有关。如果任务表现与假设的特定障碍有关，数据将支持特定神经系统在这些障碍中的作用，并支持将每项任务用作该障碍的神经行为标记。未来的研究将证实这些任务的神经相关性，扩展它们的特异性，并建立它们的临床应用。与NIMH的RDoC倡议一致，目标是使用非侵入性神经行为探测器澄清这些不同疾病背后的大脑功能障碍。这反过来又可以成为新的诊断方法的基础，以帮助指导，也许是开发新的治疗方法。

DESCRIPTION (provided by applicant): Psychiatric disorders can be diagnosed reliably, but how dysfunction in the brain leads to clinical symptoms is unclear. As recognized by the NIMH Strategic Plan, there is an urgent need to study multiple underlying brain circuits across diagnoses with the goal of identifying groups of patients with shared neural dysfunction. The ultimate goal of this approach is to use brain dysfunction, as an adjunct to clinical diagnosis, to guide the selection and development of treatments. Consistent with this approach, this 3-year R01 application proposes to use well-validated neurobehavioral tasks to examine multiple brain systems across three psychiatric disorders: social anxiety disorder (SAD), obsessive-compulsive disorder (OCD), and anorexia nervosa (AN). Although clinically different, these disorders share the feature of maladaptive behaviors organized around irrational fears. Moreover, the relationship between these disorders is hotly debated. Each disorder has been associated with different brain systems: cortico-amygdalar circuitry in SAD, fronto-striatal-pallidal circuitry in OCD, and cortico-mesolimbic circuitry in AN. The research team has experience using well-validated neurobehavioral tasks to assess the functioning of these different neural systems and the clinical expertise needed to recruit and evaluate all three types of patients. Specifically, this project will study 180 participants (40 with SAD, 40 with OCD, 40 with AN, and 60 healthy controls [HC]) using the following neurobehavioral tasks: 1) Fear extinction retention as a measure of "safety" learning (a probe of cortico-amygdalar functioning); 2) Prepulse inhibition as a measure of sensorimotor gating (a probe of cortico-striatal-pallidal functioning); and 3) Delay discounting as a measure of capacity to delay gratification (a probe of cortical-mesolimbic functioning). All 180 participants will complete all three tasks and detailed clinical assessments. This work will be completed in three years, enabling a rapid evaluation of the success of this approach. The goals are: 1) to establish that each disorder is associated with specific abnormalities on one of these tasks, as the pilot data suggest; 2) to determine whether these abnormalities are specific or shared with the other disorders; and 3) to explore whether the pattern of responses is associated with dimensional traits, clinical features, or novel groupings of cases across disorders. If task performance is associated with specific disorders as hypothesized, the data will support the role of particular neural systems in those disorders, and the use of each task as a neurobehavioral marker in that disorder. Future studies will confirm the neural correlates of these tasks, extend their specificity, and establish their clinical utility. Consistent with the RDoC initiative of NIMH, the goal is to clarify the brain dysfunction underlying these different disorders using non-invasive neurobehavioral probes. This, in turn, can be the basis for new diagnostic approaches to help guide, and perhaps develop, new treatments.