Generalized Anxiety Disorder and Social Anxiety Disorder:

广泛性焦虑症和社交焦虑症：

• 批准号: 8342150
• 负责人: james r blair
• 金额: $ 7.34万
• 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/8342150
• 关键词: Affective; Alcohol abuse; Amygdaloid structure; Anger; Anxiety; Anxiety Disorders; Coupled; Data; Decision Making; Disease; Drug abuse; Emotional; Face; Facial Expression; Fright; Functional Magnetic Resonance Imaging; Functional disorder; General Population; Generalized Anxiety Disorder; Hearing; Human; Impairment; Individual; Intervention; Lateral; Life; Medial; Mental Depression; Nature; Neurobiology; Participant; Pathology; Patients; Performance; Play; Prefrontal Cortex; Prevalence; Process; Published Comment; Punishment; Regulation; Relative (related person); Rewards; Role; Self Concept; Severities; Social Phobia; Stimulus; Suggestion; Suicide; Symptoms; Thinking; Time; Work; base; cognitive neuroscience; economic cost; follow-up; functional disability; high risk; neuromechanism; relating to nervous system; response; 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 the first study of its kind, we presented patients with GSP, patients with GAD, patients with both GSP and GAD and no pathology individuals with angry, fearful, and neutral facial expression stimuli. We demonstrated clear differences in the pathology of GAD and GSP. Patients with GSP showed significantly increased activation to fearful relative to neutral expressions in several regions, including the amygdala. In contrast, patients with GAD showed significantly reduced activation to fearful relative to neutral faces compared to healthy individuals and patients with GSP but this was coupled with anomalously and significantly increased responses in a lateral region of prefrontal cortex. Patients with comorbid GAD/GSP appeared to present with the pathology associated with the GAD, but not the GSP. Our on-going work has continued to follow this approach. Specifically, we have been examining differences in automatic and controlled emotional regulation and, more recently, self-referential processing, across these patient groups. The second strand concerns the specific nature of the functional impairment seen in GSP. Patients with GSP show increased amygdala responses to socially threatening stimuli such as fearful and angry expressions. We followed this work up by examining the neural responses to receipt of praise or criticism in GSP. Participants were presented with positive, negative, and neutral statements (e.g., You are beautiful/ ugly/ human) that could be either about highly relevant and about themselves or less relevant about somebody else (e.g., He is beautiful). The results of this study indicated an important role for not only the amygdala but also medial prefrontal cortex (MPFC) in GSP. MPFC plays an important role in self-referential processing and it now appears that GSP reflects a particular sensitivity to self-referential information. Our on-going work has followed up on these results. In particular, we have been examining the specific nature of this sensitivity to self-referential information in patients with GSP. So, for example in one study we presented participants with the statements from the first study, however, this time the statements were always self-referential and what we varied instead was whether the statements originated from others (e.g., hearing You are beautiful/ ugly/ human) or the self (e.g., thinking I am beautiful/ ugly/ human). Whereas the healthy comparison individuals in this study showed significantly increased MPFC response to the I relative to U statements, the GSP patients showed increased MPFC responses to the U relative to the I comments. Further, the responses of the patients with GSP to the I statements correlated negatively with social anxiety symptom severity. These results underscore the importance of dysfunctional self-referential processing and MPFC in GSP. We believe that these data reflect a reorganization of self-referential reasoning in the disorder with a self-concept perhaps atypically related to the view of others. 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. Using several decision making paradigms where successful performance is based on the appropriate representation of reward and punishment expectances, we observed significant impairment in patients with GAD (Devido et al., 2009). Notably, such impairments were not seen in patients with GSP. Our on-going work is following up these results and using functional magnetic resonance imaging to determine their neural basis.

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。在第一项同类研究中，我们向GSP患者、GAD患者、GSP和GAD患者以及无病理个体提供愤怒、恐惧和中性面部表情刺激。我们证明了GAD和GSP在病理学上的明显差异。GSP患者在几个区域（包括杏仁核）表现出对恐惧相对于中性表达的激活显著增加。相比之下，与健康人和GSP患者相比，GAD患者对恐惧相对于中性面孔的激活显着减少，但这与前额叶皮层外侧区域的反应显著增加相结合。GAD/GSP共病患者出现与GAD相关的病理，但与GSP无关。我们目前的工作继续遵循这一方针。具体来说，我们一直在研究自动和控制情绪调节的差异，最近，自我参照处理，在这些患者群体。 第二部分涉及普惠制中所见的功能损害的具体性质。GSP患者对社会威胁性刺激（如恐惧和愤怒的表情）的杏仁核反应增强。我们接着研究了GSP中接受表扬或批评时的神经反应。向参与者提供积极、消极和中立的陈述（例如，你是美丽的/丑陋的/人类），这可能是高度相关的和关于自己或不太相关的其他人（例如，他是美丽的）。这项研究的结果表明，不仅杏仁核，而且内侧前额叶皮质（MPFC）在GSP中也发挥着重要作用。MPFC在自我参照加工中起着重要的作用，现在看来，GSP反映了一个特殊的敏感性自我参照信息。我们正在进行的工作是根据这些结果进行的。特别是，我们一直在研究这种敏感性的具体性质，以自我参考的信息与GSP患者。 因此，例如，在一项研究中，我们向参与者展示了第一项研究中的陈述，然而，这一次的陈述总是自我指涉的，我们改变的是这些陈述是否来自他人（例如，听你是美丽的/丑陋的/人类）或自我（例如，我觉得自己很美/很丑/很人性化。 在本研究中，健康对照个体对I相对于U陈述的MPFC反应显着增加，而GSP患者对U相对于I评论的MPFC反应显着增加。 此外，GSP患者对I陈述的反应与社交焦虑症状严重程度呈负相关。这些结果强调了功能失调的自我参照处理和MPFC在GSP中的重要性。我们相信，这些数据反映了重组的自我指涉推理的障碍与自我概念，也许是相关的观点，他人。 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。使用几种决策模式，其中成功的表现是基于奖励和惩罚预期的适当表示，我们观察到GAD患者的显著损害（Devido et al.，2009年）。值得注意的是，在GSP患者中未观察到此类损伤。我们正在进行的工作是跟进这些结果，并使用功能性磁共振成像来确定其神经基础。