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.

我们与GSP和GAD患者的工作有三个重要的链。这些链中的第一个是确定GAD中看到的病理与GSP中看到的病理的程度。在对此类研究的第一项研究中，我们介绍了患有GSP的患者，患有GAD的患者，患有GSP和GAD的患者以及没有病理学的患者，患有愤怒，恐惧和中性的面部表达刺激。我们在GAD和GSP的病理学上表现出明显的差异。在包括杏仁核在内的几个地区，GSP患者相对于中性表达的恐惧表现出明显增加的激活。相比之下，与健康个体和GSP患者相比，GAD患者相对于中性面孔的激活显着降低，但在前额叶皮层的侧面区域中，异常和明显增加了反应。合并症/GSP的患者似乎伴有与GAD相关的病理学，但没有GSP。我们正在进行的工作继续遵循这种方法。具体而言，我们一直在研究这些患者群体的自动和控制情绪调节的差异，以及最近的自我指南处理。 第二链涉及在GSP中看到的功能障碍的特定性质。 GSP患者显示，杏仁核对社会威胁性刺激的反应增加，例如恐惧和愤怒的表情。我们遵循了这项工作，研究了GSP中接受赞美或批评的神经反应。向参与者展示了积极，消极和中立的陈述（例如，您是美丽/丑陋/人的），可能与他人高度相关，或与其他人相关（例如，他是美丽的）。这项研究的结果表明，不仅是杏仁核，而且对GSP中的内侧前额叶皮层（MPFC）的重要作用。 MPFC在自指处理中起着重要的作用，现在看来GSP反映了对自指信息的特殊敏感性。我们正在进行的工作已遵循这些结果。特别是，我们一直在研究GSP患者对自指信息的敏感性的特定性质。 因此，例如，在一项研究中，我们向参与者介绍了第一项研究的陈述，但是，这次陈述始终是自我指的，而我们所改变的是，这些陈述是来自其他陈述（例如，听到您是美丽/丑陋/人类）还是自我（例如，认为我是美丽/丑陋/人）。 尽管这项研究中的健康比较个体显示，相对于U对U的i对I的MPFC响应显着增加，但GSP患者显示，相对于I注释，MPFC对U的反应增加。 此外，GSP患者对I陈述的反应与社交焦虑症状的严重程度负相关。这些结果强调了GSP中功能失调的自指加工和MPFC的重要性。我们认为，这些数据反映了这种疾病中自称推理的重组，可能与他人的观点非典型地相关。 第三组工作涉及GAD中看到的功能障碍的特定性质。特别是，我们一直在研究我们在与这种疾病患者的初步工作中观察到的情感反应中的一些问题可能在决策任务上遇到困难。我们使用几种决策范式取得了成功的表现，基于奖励和惩罚期望的适当表示，我们观察到GAD患者的严重损害（Devido等，2009）。值得注意的是，在GSP患者中未见这种障碍。我们正在进行的工作正在跟进这些结果，并使用功能磁共振成像来确定其神经基础。