NEURO-GENETIC MARKERS OF SOCIAL ANXIETY DISORDER

社交焦虑症的神经遗传标志物

• 批准号: 7604782
• 负责人: K. Luan Phan
• 金额: $ 0.42万
• 依托单位: UNIVERSITY OF CHICAGO
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-03-01 至 2007-09-16
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7604782
• 关键词: Amygdaloid structure; Anxiety; Anxiety Disorders; Biological Markers; Brain; Clinical Trials; Computer Retrieval of Information on Scientific Projects Database; DNA; Disease; Exposure to; Fright; Functional Magnetic Resonance Imaging; Funding; Genetic Markers; Genetic Polymorphism; Genetic Variation; Genotype; Goals; Grant; Institution; Label; Mediating; Neurobiology; Patients; Research; Research Personnel; Resources; Selective Serotonin Reuptake Inhibitor; Sertraline; Social Phobia; Source; Stimulus; Therapeutic; United States National Institutes of Health; base; dosage; response; serotonin transporter; social

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Social anxiety disorder, also known as social phobia, is an anxiety disorder characterized by excessive fear and/or avoidance of exposure to social situations that involve potential scrutiny by others. Little is known about the pathophysiologic mechanisms that underlie social anxiety disorder, although a neurobiologic basis is strongly suspected. While selective serotonin reuptake inhibitors (SSRI) are widely used in the treatment of social anxiety disorder (SAD), as many as half of the patients with the disorder fail to respond to this first-line treatment despite adequate dosage and duration. Little is known about the neurobiological factors that would predict which patients will or will not respond to respond to treatment, and thus, guidance towards optimal therapeutic strategies remain largely uninformed. Converging evidence suggests that two related biomarkers relevant to social anxiety may be involved in mediating the therapeutic response to SSRI treatment. They are: 1) amygdala reactivity to social threat, and 2) the serotonin transporter genetic polymorphism (5-HTTLPR). The overall goal of the proposed project is to investigate whether amygdala activation to socially salient stimuli/interactions and genetic variation in the serotonin transporter polymorphism are associated with response to SSRI treatment in SAD. In the context of an open-label clinical trial of sertraline, this study consists of pre- and post-treatment fMRI of amygdala reactivity and pre-treatment DNA genotyping of the 5-HTTLPR in 80 patients with generalized SAD and 80 matched healthy controls (HC) in order to examine the relationship between these neuro-genetic markers (brain response and 5-HTTLPR genotype) and treatment response.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目及 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 社交焦虑症，也称为社交恐惧症，是一种焦虑症，其特征是过度恐惧和/或避免暴露于可能受到他人审视的社交场合。 尽管人们强烈怀疑其神经生物学基础，但人们对社交焦虑症的病理生理机制知之甚少。 虽然选择性血清素再摄取抑制剂 (SSRI) 广泛用于治疗社交焦虑症 (SAD)，但尽管剂量和持续时间足够，但仍有多达一半的患者对这种一线治疗没有反应。对于预测哪些患者会对治疗有反应或不会有反应的神经生物学因素知之甚少，因此，对最佳治疗策略的指导在很大程度上仍然不知情。综合证据表明，与社交焦虑相关的两个相关生物标志物可能参与调节 SSRI 治疗的治疗反应。它们是：1）杏仁核对社会威胁的反应性，2）血清素转运蛋白遗传多态性（5-HTTLPR）。该项目的总体目标是调查杏仁核对社会显着刺激/相互作用的激活以及血清素转运蛋白多态性的遗传变异是否与 SAD 中 SSRI 治疗的反应相关。在舍曲林的开放标签临床试验中，本研究包括对 80 名全身性 SAD 患者和 80 名匹配的健康对照 (HC) 进行治疗前和治疗后杏仁核反应性功能磁共振成像 (fMRI) 以及治疗前 5-HTTLPR 的 DNA 基因分型，以检查这些神经遗传标记（脑反应和 5-HTTLPR 基因型）与治疗反应之间的关系。