Generalized Anxiety Disorder and Social Anxiety Disorder:

广泛性焦虑症和社交焦虑症：

• 批准号: 7969417
• 负责人: james r blair
• 金额: $ 19.95万
• 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/7969417
• 关键词: Affective; Agreement; Alcohols; American; Amygdaloid structure; Anger; Anxiety; Anxiety Disorders; Archives; Caring; Categories; Choking; Classification; Commit; Coughing; Coupled; Data; Decision Making; Development; Disease; Disease model; Dissociation; Drug Formulations; Drug abuse; Face; Facial Expression; Food; Fright; Functional Magnetic Resonance Imaging; Functional disorder; Future; General Population; Generalized Anxiety Disorder; Human; Hyperactive behavior; Impairment; Individual; Intervention; Journals; Lateral; Life; Medial; Mediating; Medicine; Neurobiology; Paper; Participant; Pathology; Patients; Pattern; Perception; Population; Prefrontal Cortex; Prevalence; Psychiatry; Psychological reinforcement; Publications; Published Comment; Publishing; Recruitment Activity; Relative (related person); Role; Social Phobia; Stimulus; Subgroup; Suggestion; Suicide; Therapeutic; Time; Work; base; cognitive neuroscience; depression; design; economic cost; high risk; neural circuit; neuromechanism; novel; psychologic; relating to nervous system; response; social; therapeutic target

Our work has been important in suggesting that GAD and GSP are indeed associated with different pathophysiologies. In recent work, we presented patients with GSP, patients with GAD, and no pathology individuals with angry, fearful, and neutral facial expression stimuli. Our data clearly suggested that the neural circuitry dysfunction in GSP and GAD differ. Specifically, we found that 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. Importantly, a secondary analysis conducted with the subgroup of patients with comorbid GAD/GSP indicated that they presented with the pathologies associated with the GAD, but not the GSP. That is, these preliminary results strongly suggest the importance of a systematic examination and comparison of GSP, GAD, and comorbid GAD/GSP for a fuller disorder-specific understanding and development of new treatment targets. This paper was published in The American Journal of Psychiatry in 2008. In other recent work, we examined the neural responses to receipt of praise or criticism in GSP and GAD within a newly design novel statement paradigm. 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). There were again two major results. First, there again was a clear double dissociation between the individuals with GSP and GAD with suggestions of a divergent subcortical response to social stimuli in the two populations. Second, the results indicated an important role for self-relevance and medial prefrontal cortex (MPFC), mediating self-relevance, in GSP. Thus, on this task patients with GSP showed significantly increased neural responses in MPFC and amygdala to negative comments about the self (criticism). However, the groups did not differ significantly in their neural responses to any of the other statement categories: neutral or positive comments about the self, or negative, neutral, or positive comments about others. This paper was published in the Archives of General Psychiatry in 2008. In subsequent work, we considered whether the increased neural responses in GSP to negative comments about the self reflects (a) increased agreement with those comments, and/or (b) increased concern or mentalizing about others negative perceptions. Participants were presented again with positive, negative, and neutral statements (e.g., You are beautiful/ ugly/ human) but this time they were always self relevant, and instead we manipulated whether the comments came from somebody else (e.g., You are beautiful), or was internally generated (e.g., I am beautiful). The results further underlined the critical role of MPFC in GSP pathology, and again demonstrated a meaningful effect of psychological context on neural-circuitry hyperactivity in GSP. Thus, on this modified comment task, patients with GSP showed significantly increased activation in MPFC to comments that came from somebody else (i.e., You comments), however, they did not show increased neural responses to comments that originated within the self (i.e., I comments). This paper is currently being prepared for publication. The importance of MPFC and contextual information in GSP was further demonstrated in other recent work, where we examined the neural response to social situations that could either involve an intentional transgression (e.g., Joanna does not like her food and spits it out), or an unintentional (embarrassing) transgression (e.g., Joanna chokes on her food and coughs it up). People with no social anxiety typically show increased MPFC responses to the intentional social transgressions, presumably because those acts typically involve more severe consequences (i.e., using the Joanna example, spitting out the food will anger the host, but coughing up the food will probably not have consequences). However, in our study patients with GSP showed the opposite pattern with increased MPFC responses to unintentional transgressions, presumably because (1) they care more about causing embarrassment, than anger, and (2) the intentional stories are not relevant to them because they are extremely unlikely to intentionally commit a social transgression. This highly context dependent response in GSP helps constrain existing models of the disorder and may thus guide future therapeutic formulations in the treatment of the disorder. This paper is currently being prepared for publication. In other recent work, we examined stimulus-reinforcement based decision making using a task that has previously been demonstrated to recruit the amygdala and vmPFC in healthy individuals. The data on this task also indicated a dissociation between GAD and GSP. Thus, only patients with GAD showed impairment on this task (relative to both patients with GSP and healthy individuals who did not significantly differ). Moreover, the patients with comorbid GAD/GSP also showed significant impairment on the task (relative to both patients with GSP and healthy individuals). However, the patients with comorbid GAD/GSP and those with GAD alone did not show significant differences in impairment. Thus, this work has underlined the importance of determining the separable pathophysiologies associated with the individual conditions. This paper was published in Psychological Medicine in 2009.

我们的工作对于暗示GAD和GSP确实与不同的病理生理相关的工作非常重要。在最近的工作中，我们介绍了患有GSP，患有GAD的患者，没有病理学患者，患有愤怒，恐惧和中性面部表达刺激的患者。我们的数据清楚地表明，GSP和GAD中的神经回路功能障碍有所不同。具体而言，我们发现GSP患者在包括杏仁核在内的多个地区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。重要的是，与合并症/GSP患者亚组进行的二次分析表明，他们呈现了与GAD相关的病理学，但没有GSP。也就是说，这些初步结果强烈表明了对GSP，GAD和合并症GAD/GSP进行系统检查和比较的重要性，以便对新治疗靶标有特定于疾病的特定理解和开发。 本文于2008年发表在《美国精神病学杂志》上。 在最近的其他工作中，我们研究了在新设计的小说陈述范式中，在GSP和GAD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）。再次有两个主要结果。首先，在两个人群中，具有GSP和GAD的个体之间的同皮下反应有分歧的皮层反应，这再次是明显的双重分离。其次，结果表明，在GSP中，自相关和内侧前额叶皮层（MPFC）（MPFC）的重要作用。因此，在这项任务上，患有GSP的患者对MPFC和杏仁核的神经反应显着增加，对关于自我的负面评论（批评）。但是，这些群体在对其他任何陈述类别的神经反应中没有显着差异：对自我或对他人的消极，中立或积极评论的中性或积极评论。 本文于2008年发表在《普通精神病学档案》上。 在随后的工作中，我们考虑了GSP中对自我负面评论的神经反应增加是否反映了（a）与这些评论的同意增加，以及/（b）对他人负面看法的关注或心理增加。 再次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），但是这次他们总是与自我相关，相反，我们操纵了这些评论是来自其他人（例如，您是美丽的），还是内部产生的（例如，我很漂亮）。 结果进一步强调了MPFC在GSP病理学中的关键作用，并再次证明了心理环境对GSP中神经通路多动的有意义的影响。 因此，在这项修改后的评论任务上，GSP患者在MPFC中显示出来自其他人的评论的激活显着增加（即您的评论），但是，他们没有显示出对起源于自我（即我评论）评论的神经反应的增加。 本文目前正在准备出版。 在最近的其他工作中进一步证明了MPFC和GSP中情境信息的重要性，在那里我们检查了对社交状况的神经反应，这些反应可能涉及有意犯罪（例如，乔安娜不喜欢她的食物并吐出自己的食物），或者吐出它），或者是无意的（尴尬的）传播（例如，乔安娜（Joanna）对她的食物（例如，乔安娜（Joanna chokes））对她的食物和她的食物cho ch）。 没有社交焦虑的人通常会显示出MPFC对故意社会犯罪的反应增加，这大概是因为这些行为通常涉及更严重的后果（即，使用乔安娜的例子，吐出食物会激怒宿主，但咳嗽的食物可能不会产生后果）。 但是，在我们的研究中，患有GSP的患者表现出相反的模式，MPFC对无意违法的反应增加，大概是因为（1）他们更关心造成尴尬，而不是愤怒，并且（2）故意的故事与他们无关，因为它们极不可能故意犯下社交侵犯。 GSP中这种高度背景的反应有助于限制现有的疾病模型，因此可以指导将来的治疗疾病治疗中的治疗表述。本文目前正在准备出版。 在最近的其他工作中，我们研究了基于刺激 - 强化的决策做出，该任务以前已被证明是在健康个体中招募杏仁核和VMPFC。有关此任务的数据还表明GAD和GSP之间存在解离。因此，只有GAD患者在这项任务上显示出障碍（相对于GSP患者和没有显着差异的健康个体患者）。此外，合并症/GSP的患者在任务上也显示出严重的损害（相对于患有GSP和健康个体的患者）。但是，合并症GAD/GSP和单独使用GAD的患者在损伤方面没有显着差异。因此，这项工作强调了确定与个人条件相关的可分离病理生理的重要性。 本文于2009年发表在心理医学上。