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 患者的工作分为三个重要部分。第一条是确定 GAD 中所见病理学与 GSP 中所见病理学的不同程度。在此类研究中，我们为 GSP 患者、GAD 患者、同时患有 GSP 和 GAD 的患者以及无病理个体提供了愤怒、恐惧和中性的面部表情刺激。我们证明了 GAD 和 GSP 病理学上的明显差异。与中性表达相比，GSP 患者在多个区域（包括杏仁核）的恐惧表达显着增加。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恐惧激活显着减少，但这与前额皮质外侧区域异常且显着增加的反应相结合。患有 GAD/GSP 共病的患者似乎表现出与 GAD 相关的病理，但与 GSP 无关。我们正在进行的工作继续遵循这种方法。具体来说，我们一直在研究这些患者群体在自动和受控情绪调节以及最近的自我参照处理方面的差异。 第二条涉及 GSP 中所见功能损伤的具体性质。 GSP 患者表现出杏仁核对社交威胁刺激（例如恐惧和愤怒的表情）的反应增强。我们通过检查普惠制中受到赞扬或批评的神经反应来跟进这项工作。向参与者提供积极、消极和中性的陈述（例如，你很漂亮/丑陋/人类），这些陈述可能与他们自己高度相关，也可能与其他人不太相关（例如，他很漂亮）。这项研究的结果表明，在 GSP 中，杏仁核和内侧前额叶皮层 (MPFC) 都发挥着重要作用。 MPFC 在自我参照处理中发挥着重要作用，现在看来，GSP 反映了对自我参照信息的特殊敏感性。我们正在进行的工作就是对这些结果的跟进。特别是，我们一直在研究普惠制患者对自我参照信息的敏感性的具体性质。 因此，例如在一项研究中，我们向参与者提供了第一项研究中的陈述，然而，这一次这些陈述总是自我指涉的，我们改变的是这些陈述是否源自他人（例如，听到你很漂亮/丑陋） /人类）或自我（例如，认为我很漂亮/丑陋/人类）。 虽然本研究中的健康对照个体显示 MPFC 对 I 的反应相对于 U 语句显着增加，但 GSP 患者显示 MPFC 对 U 的反应相对于 I 评论增加。 此外，GSP 患者对 I 语句的反应与社交焦虑症状的严重程度呈负相关。这些结果强调了 GSP 中功能失调的自我参照处理和 MPFC 的重要性。我们认为，这些数据反映了这种疾病中自我参照推理的重组，其自我概念可能与他人的观点非典型相关。 第三部分工作涉及广泛性焦虑症中所见功能障碍的具体性质。特别是，我们一直在研究我们在对广泛性焦虑症患者的初步研究中观察到的一些情绪反应问题是否可能表现为决策任务的困难。使用几种决策范例，其中成功的表现基于奖励和惩罚预期的适当表示，我们观察到广泛性焦虑症患者的显着损害（Devido 等，2009）。值得注意的是，在 GSP 患者中并未发现此类损伤。我们正在进行的工作是跟踪这些结果并使用功能磁共振成像来确定它们的神经基础。