Neural circuitry of submissive behavior and treatment response in social anxiety

描述（由申请人提供）：社交焦虑障碍（SAD）是一种普遍存在的致残性疾病，其神经生物学仍然知之甚少。本研究的目的是确定一种与SAD相关的新型内表型及其对治疗反应的生物标志物，可用于动物模型和人类的进一步研究，以提高对SAD病因的理解并推进其治疗。对注视的恐惧是SAD的核心症状，它似乎与进化保守的顺从行为有关，例如避免直接注视和对社会威胁的警惕。威胁性的面部表情（特别是如果隐式处理），激活SAD中涉及感知社会视觉线索的神经回路，但眼睛凝视刺激很少被研究。此外，凝视和面部表情刺激尚未用于识别SAD治疗相关的神经激活变化。这项研究将评估SAD患者治疗前后的神经回路激活情况，使用fMRI和两组刺激：1）一组新的面部照片，逼真地模拟眼睛运动到直接或间接凝视; 2）情绪面部表情照片。我们假设，在SAD患者中，用直接眼睛凝视的面孔处理和愤怒的面部表情处理将优先激活恐惧电路结构，例如杏仁核和脑岛、相关的额叶区域（喙侧前扣带回和内侧前额叶皮质）以及视觉面孔处理的核心区域（梭状回）。我们进一步假设这些区域的激活与这些患者SAD的严重程度相关，并且在用5-羟色胺再摄取抑制剂（SSRI）药物治疗后，这些区域的激活将正常化，并且正常化的程度将与症状改善的程度相关。将使用fMRI评估20名全身性SAD受试者和20名匹配的健康对照（HC）受试者对直接与间接注视以及对愤怒和中性面部表情的内隐与外显处理的神经回路激活。将使用眼动追踪设备评估fMRI期间的凝视回避，并将其用作fMRI分析的协变量。SAD受试者完成SSRI药物急性治疗后，受试者将在12周后重复相同的程序。如果威胁神经回路激活与SAD中的直接眼睛注视相关，并且降低的激活与治疗反应相关，则这将支持对动态直接注视刺激的反应作为适合于在患有SAD和其他病症的动物模型和人类中进一步研究的内表型。7.项目叙述社交焦虑障碍是一种普遍的致残性疾病，其神经生物学仍然知之甚少。本研究的目的是确定这种疾病的生物标志物及其对治疗的反应，可用于动物模型和人类的进一步研究，并最终改善社交焦虑症的诊断和治疗。

DESCRIPTION (provided by applicant): Social anxiety disorder (SAD) is a prevalent and disabling condition whose neurobiology remains poorly understood. The goal of this study is to identify a novel endophenotype associated with SAD and a biomarker of its response to treatment that could be used for further research in animal models and humans to improve understanding of the causes of SAD and to advance its treatment. Fear of eye gaze is a core symptom of SAD that appears related to evolutionarily-conserved submissive behaviors, such as avoidance of direct gaze and vigilance for social threat. Threatening facial expressions (especially if implicitly processed), activate neural circuits in SAD involved with perceiving social visual cues, but eye gaze stimuli have been little studied. Also, gaze and facial expression stimuli have not yet been used to identify SAD treatment-related changes in neural activation. This study will assess neural circuitry activation in SAD, before and after treatment, using fMRI with two sets of stimuli: 1) a novel set of face photos that realistically simulate eye motion into direct or indirect gaze; and 2) emotional facial expression photos. We hypothesize that in SAD patients, processing of faces with direct eye gaze and processing of angry facial expressions will preferentially activate fear circuitry structures such as the amygdala and insula, associated frontal regions (rostral anterior cingulate and medial prefrontal cortex), and core areas of visual face processing (fusiform gyrus). We further hypothesize that activation of these regions will be correlated with severity of SAD in these patients, and that after treatment with serotonin reuptake inhibitor (SSRI) medication, these regional activations will normalize, and the extent of normalization will be correlated with the extent of symptomatic improvement. Twenty subjects with generalized SAD and 20 matched healthy comparison (HC) subjects will be assessed with fMRI for activation of neurocircuitry in response to direct vs. indirect gaze, and to implicit vs. explicit processing of angry and neutral facial expressions. Gaze avoidance during fMRI will be assessed using an eye tracking device and utilized as a covariate in fMRI analyses. Subjects will repeat the same procedures 12 weeks later, after SAD subjects have completed acute treatment with SSRI medication. If threat neurocircuitry activation is associated with direct eye gaze in SAD and decreased activation is associated with treatment response, this would support the response to dynamic direct gaze stimuli as an endophenotype suitable for further study in animal models and humans with SAD and other disorders. 7. Project Narrative Social anxiety disorder is a prevalent and disabling condition whose neurobiology remains poorly understood. The goal of this study is to identify a biological marker of this disorder and its response to treatment that could be used for further research in animal models and humans, and ultimately to improve the diagnosis and treatment of social anxiety disorder.