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.

我们的工作很重要，表明 GAD 和 GSP 确实与不同的病理生理学相关。在最近的工作中，我们向 GSP 患者、GAD 患者和无病理个体呈现愤怒、恐惧和中性的面部表情刺激。我们的数据清楚地表明 GSP 和 GAD 的神经回路功能障碍有所不同。具体来说，我们发现，GSP 患者在几个区域（包括杏仁核）表现出相对于中性表达的恐惧激活显着增加。相比之下，与健康个体和患有 GSP 的患者相比，患有 GAD 的患者表现出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。重要的是，对患有 GAD/GSP 共病的患者亚组进行的二次分析表明，他们表现出与 GAD 相关的病理，但与 GSP 无关。也就是说，这些初步结果强烈表明系统检查和比较 GSP、GAD 和共病 GAD/GSP 对于更全面地了解特定疾病和开发新治疗靶点的重要性。 该论文于2008年发表在《美国精神病学杂志》上。 在最近的其他工作中，我们在新设计的新颖陈述范式中检查了 GSP 和 GAD 对受到赞扬或批评的神经反应。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）。再次有两个主要结果。首先，GSP 和 GAD 个体之间再次存在明显的双重分离，这表明这两个人群对社会刺激的皮层下反应不同。其次，结果表明自我相关性和内侧前额叶皮层（MPFC）在 GSP 中发挥重要作用，调节自我相关性。因此，在这项任务中，GSP 患者的 MPFC 和杏仁核对自我负面评论（批评）的神经反应显着增强。然而，各组对任何其他陈述类别的神经反应没有显着差异：对自我的中立或积极评论，或对他人的消极、中立或积极评论。 这篇论文于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 对自我负面评论的神经反应增加是否反映了（a）与这些评论的一致性增加，和/或（b）对他人负面看法的担忧或心理化增加。 参与者再次收到积极、消极和中性的陈述（例如，你很美丽/丑陋/人类），但这一次它们总是与自身相关，相反，我们操纵这些评论是来自其他人（例如，你很美丽），还是内部产生的（例如，我很美丽）。 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 中神经回路过度活跃的有意义的影响。 因此，在这个修改后的评论任务中，GSP 患者的 MPFC 对来自其他人的评论（即“你的评论”）的激活显着增加，然而，他们并没有表现出对源自自我的评论（即“我的评论”）的神经反应增加。 这篇论文目前正在准备出版。 MPFC 和 GSP 中的情境信息的重要性在最近的其他工作中得到了进一步证明，我们检查了对社交情境的神经反应，这些社交情境可能涉及故意的越轨（例如，乔安娜不喜欢她的食物并将其吐出来），或无意的（令人尴尬的）越轨（例如，乔安娜被食物噎住并将其咳出）。 没有社交焦虑的人通常会对故意的社交违规表现出更强的 MPFC 反应，大概是因为这些行为通常会带来更严重的后果（即，用乔安娜的例子，吐出食物会激怒主人，但咳出食物可能不会产生后果）。 然而，在我们的研究中，GSP 患者表现出相反的模式，MPFC 对无意的越轨反应增加，大概是因为 (1) 他们更关心造成尴尬，而不是愤怒，(2) 故意的故事与他们无关，因为他们极不可能故意犯下社会越轨行为。 GSP 中这种高度背景依赖性的反应有助于限制现有的疾病模型，从而可以指导未来治疗该疾病的治疗配方。这篇论文目前正在准备出版。 在最近的其他工作中，我们使用先前已被证明可以在健康个体中募集杏仁核和 vmPFC 的任务来检查基于刺激强化的决策。该任务的数据还表明 GAD 和 GSP 之间存在分离。因此，只有 GAD 患者在这项任务上表现出障碍（相对于 GSP 患者和健康个体，没有显着差异）。此外，患有 GAD/GSP 共病的患者在任务上也表现出显着的损害（相对于患有 GSP 的患者和健康个体）。然而，合并 GAD/GSP 的患者和单独患有 GAD 的患者在损伤方面没有表现出显着差异。因此，这项工作强调了确定与个体状况相关的可分离病理生理学的重要性。 该论文于2009年发表在《心理医学》杂志上。