PET Imaging of OFC and Amygdala in Panic Disorder

恐慌症中 OFC 和杏仁核的 PET 成像

• 批准号: 7032622
• 负责人: MONTE Stuart BUCHSBAUM
• 金额: $ 44.45万
• 依托单位: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-04-15 至 2009-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7032622
• 关键词: amygdala; anxiety disorders; bioimaging /biomedical imaging; brain imaging /visualization /scanning; clinical research; cognitive behavior therapy; fear; human subject; hyperpnea; neuroendocrine system; neurophysiology; panic disorder; patient oriented research; positron emission tomography; prefrontal lobe /cortex; vasoconstriction; vasoconstrictors

DESCRIPTION (provided by applicant): This is a second resubmission to study the response of the amygdala and orbitofrontal cortex (OFC) in patients with panic disorder (PD) to anticipatory anxiety and panic states using FOG-PET. Preclinical research has demonstrated that the amygdala is a crucial brain structure for the acquisition and expression of conditioned fear. Several different brain imaging methods have been employed to show that amygdala activation commonly occurs during the induction of fear and anxiety in humans. Some studies suggest that the threshold for amygdala activation is lower in anxiety disorder patients. Several preclinical studies have also now shown that areas within the prefrontal cortex exert control over the amygdala. Neuroimaging data also indicate this in humans and-that 1 feature of anxiety disorder patients is an alteration in activity of prefrontal cortical areas, including the anterior cingulate and the OFC. In a PET study using 15O-H20 we found that immediately prior to the administration of doxapram, which reliably produces panic attacks in PD patients but not controls, subjects who subsequently panicked after doxapram administration showed marked reduction in OFC activity. This finding indicates the need to further study the relationship between the amygdala and prefrontal cortex in PD patients. The substantial vasoconstriction caused by doxapram-induced hyperventilation made it impossible to image amygdala activation during the actual panic attack. Therefore, by adapting FDG PET to doxapram administration in a pilot study that measures metabolic rate instead of blood flow, we are able to image the amygdala and OFC during panic attacks. Our pilot data show that PD patients demonstrate increased amygdala activation more than controls during doxapram administration, but unexpectedly also show increased OFC metabolic rate. Cognitive behavioral therapy (CBT) normalized the patients' OFC response. We speculate that CBT modifies prefrontal cortical activity thereby restoring normal interaction with the amygdala. We propose to study PD patients and matched normal comparison subjects who will undergo FDG PET scans during resting, placebo, and doxapram administration. We predict that while anticipating panic, patients will show altered OFC metabolic rate compared to controls and that during doxapram administration panicking patients will show altered amygdala activation compared to non-panicking subjects. We will also look for correlations between these brain metabolic analyses and changes in autonomic, neuroendocrine, and subjective anxiety measures. Patients will then be treated with CBT and the PET scans repeated. We predict that successful treatment will lead to a normalization in OFC and doxapram-induced amygdala activity. We have added assessment of anxious anticipation and anxious arousal at the different stages of the experiment and several design changes to insure the maintenance when appropriate of an anticipatory state. The study aims to further understanding of the neuroanatomical substrate of panic attacks and to establish a possible mechanism of action for successful CBT.

描述（由申请人提供）：这是第二次重新提交，旨在使用FOG-PET研究惊恐障碍（PD）患者的杏仁核和眶额皮质（OFC）对预期焦虑和惊恐状态的反应。临床前研究已经证明，杏仁核是获得和表达条件性恐惧的关键大脑结构。几种不同的大脑成像方法已经被用来表明杏仁核的激活通常发生在人类恐惧和焦虑的诱导过程中。一些研究表明，焦虑症患者的杏仁核激活阈值较低。几项临床前研究也表明，前额皮质内的区域对杏仁核起着控制作用。神经影像学数据也表明了这一点，焦虑症患者的一个特征是前额叶皮质区的活动改变，包括前扣带回和眶额皮层。在使用15 O-H20的PET研究中，我们发现，在给予多沙普仑之前，多沙普仑在PD患者中可靠地产生惊恐发作，而不是对照，随后在多沙普仑给药后恐慌的受试者显示OFC活性显著降低。这一发现表明，需要进一步研究帕金森病患者杏仁核和前额叶皮质之间的关系。多沙普仑引起的过度换气引起的大量血管收缩使得在实际的惊恐发作期间不可能想象杏仁核激活。因此，在一项测量代谢率而不是血流量的初步研究中，通过将FDG PET调整为多沙普仑给药，我们能够在惊恐发作期间对杏仁核和OFC进行成像。我们的初步数据显示，PD患者在多沙普仑给药期间表现出比对照组更多的杏仁核激活，但出乎意料地也显示出OFC代谢率增加。认知行为疗法（CBT）使患者的OFC反应正常化。我们推测，认知行为疗法改变了前额叶皮层的活动，从而恢复了与杏仁核的正常互动。我们建议研究PD患者和匹配的正常对照受试者，他们将在静息、安慰剂和多沙普仑给药期间接受FDG PET扫描。我们预测，在预期恐慌的同时，患者将显示与对照组相比OFC代谢率的改变，并且在多沙普仑给药期间，与非恐慌受试者相比，恐慌患者将显示杏仁核激活的改变。我们还将寻找这些大脑代谢分析与自主神经，神经内分泌和主观焦虑指标变化之间的相关性。然后，患者将接受CBT治疗，并重复PET扫描。我们预测，成功的治疗将导致正常化的OFC和多沙普仑诱导的杏仁核活动。我们在实验的不同阶段增加了对焦虑预期和焦虑唤醒的评估，并对设计进行了一些修改，以确保在适当的时候维持预期状态。该研究旨在进一步了解惊恐发作的神经解剖学基础，并建立成功CBT的可能作用机制。