Generalized Anxiety Disorder and Social Anxiety Disorder:

广泛性焦虑症和社交焦虑症：

• 批准号: 8745722
• 负责人: james r blair
• 金额: $ 14.39万
• 依托单位: NATIONAL INSTITUTE OF MENTAL HEALTH
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/8745722
• 关键词: Affective; Alcohol abuse; Amygdaloid structure; Anxiety Disorders; Decision Making; Development; Disease; Drug abuse; Emotional; Event; Fright; Functional Magnetic Resonance Imaging; Functional disorder; General Population; Generalized Anxiety Disorder; Impairment; Individual; Intervention; Learning; Life; Maintenance; Medial; Mental Depression; Nature; Neurobiology; Pathology; Patients; Phobic anxiety disorder; Population; Prefrontal Cortex; Prevalence; Probability; Process; Reaction; Role; Social Environment; Social Phobia; Stimulus; Suggestion; Suicide; Work; base; cognitive neuroscience; economic cost; emotional reaction; frontal lobe; functional disability; high risk; neuromechanism; relating to nervous system; response; showing emotion; social; therapeutic target

There are three important strands to our work with patients with GSP and GAD: The first of these strands is determining the degree to which the pathology seen in GAD differs from that seen in GSP. In previous work, we were the first to demonstrate that patients with GSP and GAD differ in their responsiveness to emotional expression stimuli. Specifically, we showed that the heightened amygdala response to fearful expressions seen in GSP is not seen in patients with GAD. Indeed, they show indications of hypo-responsiveness. Over the past year, we have extended these results in two important ways: (a) only patients with GAD and not those with GSP show reduced optimistic bias. This appears to reflect dysfunction in the role of rostral medial frontal cortex in comparison processes; and (b) only patients with GSP and not those with GAD show dysfunction in the context of social referencing. Social referencing refers to the process by which an individual learns the value of objects and actions by witnessing another's reactions to them. The second strand concerns the specific nature of the functional impairment seen in GSP. In previous work, we have shown that GSP does not simply represent a heightened amygdala response to social threats. Instead, there appears additionally to be atypical self referential processing of social information. In short, our earlier work had indicated an important role for not only the amygdala but also medial prefrontal cortex (MPFC a region critical for self referential processing) in GSP. This year, we extended this work by showing that patients with GSP show heightened amygdala and medial prefrontal cortex responses when engaged in social referencing (watching another show an emotional reaction to an object) than comparison populations. In addition, patients with GSP show heightened amygdala responses to objects associated with another individuals emotional displays. Importantly, social referencing is thought to be important for the development and maintenance of phobias and the impairment may contribute to the persistence of this disorder. The third strand of work concerns the specific nature of the functional impairment seen in GAD. In particular, we have been examining whether some of the problems in emotional responding in GAD that we observed in our preliminary work with patients with this disorder might manifest in difficulties on decision making tasks. Following on from our previous results, we developed an optimistic bias task suitable for fMRI. Optimistic bias refers to the tendency of healthy individuals to consider that good things are more likely to occur to them, and bad things less likely to occur to them, than is statistically probable. Reduced optimistic bias is seen in depression and we showed that it is also seen in GAD but not GSP. Importantly, we identified the neuro-computational impairment that may underpin the impairment in GAD. Specifically, the role of rostral medial frontal cortex in the comparison of valenced event probabilities appears to be disrupted in GAD.

我们对GSP和GAD患者的工作有三个重要方面： 第一条是确定GAD中所见病理与GSP中所见病理的不同程度。在以前的工作中，我们是第一个证明GSP和GAD患者对情绪表达刺激的反应不同。具体来说，我们发现，在GSP中看到的杏仁核对恐惧表情的反应增强，在GAD患者中没有看到。事实上，它们显示出低反应性的迹象。在过去的一年里，我们在两个重要方面扩展了这些结果：（a）只有GAD患者而不是GSP患者表现出乐观偏差减少。这似乎反映了在比较过程中，吻侧内侧额叶皮质的作用功能障碍;（B）只有GSP患者而非GAD患者在社会参照的背景下表现出功能障碍。社会参照指的是一个人通过目睹他人对他们的反应来学习物体和行动的价值的过程。 第二部分涉及普惠制中所见的功能损害的具体性质。在以前的工作中，我们已经表明，GSP并不仅仅代表了杏仁核对社会威胁的反应。相反，似乎还存在非典型的社会信息的自我参照处理。简而言之，我们早期的工作表明，不仅杏仁核，而且内侧前额叶皮层（MPFC是自我参照处理的关键区域）在GSP中起着重要作用。今年，我们扩展了这项工作，表明GSP患者在参与社会参照（观看另一个人对某个物体表现出情绪反应）时，杏仁核和内侧前额叶皮层的反应比对照人群高。 此外，GSP患者对与另一个人的情绪表现相关的物体表现出杏仁核反应增强。 重要的是，社会参照被认为对恐惧症的发展和维持很重要，而这种损害可能导致这种疾病的持续存在。 第三部分工作涉及GAD中所见的功能障碍的具体性质。特别是，我们一直在研究是否在GAD的情绪反应，我们观察到在我们的初步工作与这种疾病的患者的一些问题可能会表现在决策任务的困难。根据我们以前的结果，我们开发了一个适合fMRI的乐观偏见任务。乐观偏见是指健康个体倾向于认为好事更有可能发生在他们身上，坏事不太可能发生在他们身上，而不是统计上的可能性。在抑郁症中可以看到减少的乐观偏见，我们发现它也可以在GAD中看到，但不是GSP。重要的是，我们确定了可能支持GAD损伤的神经计算损伤。具体来说，喙内侧额叶皮层的作用，在比较valenced事件的概率似乎被打乱在广泛性焦虑症。