Neuro-Genetic Markers of SSRI Treatment Response in Social Anxiety Disorder

社交焦虑症 SSRI 治疗反应的神经遗传标志物

• 批准号: 7239577
• 负责人: K. Luan Phan
• 金额: $ 5.47万
• 依托单位: UNIVERSITY OF CHICAGO
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-06-02 至 2007-10-05
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7239577
• 关键词: Aftercare; Alleles; Amygdaloid structure; Anger; Anxiety; Anxiety Disorders; Biological Markers; Brain; Brain imaging; Chronic; Clinical; Clinical Trials; DNA; Data; Disease; Dose; Emotions; Exhibits; Face; Fright; Functional Magnetic Resonance Imaging; Genes; Genetic; Genetic Markers; Genetic Polymorphism; Genetic Variation; Genotype; Goals; Knowledge; Label; Mediating; Mental disorders; Mentored Patient-Oriented Research Career Development Award; Mentors; Modality; Neurobiology; Neurosciences; Patients; Pharmaceutical Preparations; Pharmacogenetics; Play; Probability; Process; Psychopharmacology; Relative (related person); Research; Research Personnel; Research Project Grants; Research Training; Role; Selective Serotonin Reuptake Inhibitor; Sertraline; Severities; Stimulus; Symptoms; Therapeutic; Training; Treatment Efficacy; Variant; base; depressive symptoms; dosage; neurophysiology; programs; response; serotonin transporter; showing emotion; skills; social; social cognition; success; training project

DESCRIPTION (provided by applicant): Project Summary: Through this Mentored Patient-Oriented Research Career Development Award (K23), the long-term objective of the candidate is to gain proficiency in research on the neurobiology and treatment of social anxiety disorder (SAD). Although approximately half of patients with SAD fail to respond to first-line selective serotonin reuptake inhibitor (SSRI) treatment despite adequate dose and duration, little is known about the neurophysiological mechanisms underlying treatment efficacy. Converging evidence suggests that amygdala reactivity to social threat and a functional polymorphism on the serotonin transporter gene (5-HTTLPR) are potential biomarkers of SSRI treatment response. The proposed research training and project focus on elucidating the neuro-genetic basis of pharmacologic treatment response in SAD through the application of brain functional magnetic resonance imaging (fMRI) and pharmacogenetics. To accomplish this goal, the candidate will build on his strong background in brain imaging of emotions and gain additional mentoring by experts in the fields of clinical psychopharmacology, pharmacogenetics, and SAD. Furthermore, the candidate will participate in formal coursework and carry out a research project closely aligned with his research training goals. In the context of an open-label clinical trial of sertraline, this study proposes to perform pre- and post-treatment fMRI of amygdala reactivity to harsh/negative face stimuli and pre-treatment DNA genotyping of the 5- HTTLPR in 80 patients with generalized SAD and 40 matched healthy controls in order to examine the relationship between these neuro-genetic markers and treatment response. By implementing this research project and training plan, the candidate will gain sufficient knowledge and skills to become an independent translational clinical neuroscience investigator in the field of social anxiety disorder, and advance our knowledge on the effect of genes on neurophysiology and treatment of anxiety disorders. Relevance: Social anxiety disorder is a highly prevalent, disabling, and difficult-to-treat chronic mental illness. The primary goal of this research is to identify neurobiological markers of treatment responsiveness in order to save patients costly and lengthy trials of medications that are unlikely to be effective and guide treatment towards modalities that have a greater probability of success.

描述（由申请人提供）： 项目摘要：通过这项以患者为导向的研究职业发展奖（K23），候选人的长期目标是熟练掌握神经生物学研究和社交焦虑症（SAD）的治疗。虽然大约一半的 SAD 患者对一线选择性血清素再摄取抑制剂 (SSRI) 治疗没有反应，尽管剂量和持续时间足够，但人们对治疗效果背后的神经生理学机制知之甚少。综合证据表明，杏仁核对社会威胁的反应性和血清素转运蛋白基因 (5-HTTLPR) 的功能多态性是 SSRI 治疗反应的潜在生物标志物。拟议的研究培训和项目重点是通过应用脑功能磁共振成像 (fMRI) 和药物遗传学来阐明 SAD 药物治疗反应的神经遗传学基础。为了实现这一目标，候选人将利用其在情绪大脑成像方面的强大背景，并获得临床精神药理学、药物遗传学和 SAD 领域专家的额外指导。此外，候选人将参加正式课程并开展与其研究培训目标密切相关的研究项目。在舍曲林开放标签临床试验的背景下，本研究拟对 80 名广泛性 SAD 患者和 40 名匹配的健康对照者进行治疗前和治疗后杏仁核对严酷/消极面部刺激的反应性 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物与治疗反应之间的关系。通过实施该研究项目和培训计划，候选人将获得足够的知识和技能，成为社交焦虑症领域的独立转化临床神经科学研究人员，并增进我们对基因对神经生理学和焦虑症治疗的影响的认识。相关性：社交焦虑症是一种非常普遍、致残且难以治疗的慢性精神疾病。这项研究的主要目标是确定治疗反应性的神经生物学标志物，以便为患者节省昂贵且漫长的不太可能有效的药物试验，并指导治疗采取更有可能成功的方式。