Neurofunctional Predictors of Treatment Response in Adolescents with GAD

青少年广泛性焦虑症 (GAD) 治疗反应的神经功能预测因素

• 批准号: 8806269
• 负责人: Jeffrey Robert Strawn
• 金额: $ 18.63万
• 依托单位: UNIVERSITY OF CINCINNATI
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-09-23 至 2018-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8806269
• 关键词: Adolescence; Adolescent; Affect; Amygdaloid structure; Anterior; Antidepressive Agents; Anxiety; Anxiety Disorders; Award; Biological Markers; Biometry; Brain; Brain imaging; Caring; Child; Childhood; Clinical; Coupled; Data; Depressive disorder; Disease; Double-Blind Method; Early treatment; Emotional; Emotions; Escitalopram; Fostering; Fright; Functional Magnetic Resonance Imaging; Functional disorder; Generalized Anxiety Disorder; Goals; High Prevalence; Intervention; Knowledge; Life; Longitudinal Studies; Magnetic Resonance Imaging; Measures; Mental disorders; Mentored Patient-Oriented Research Career Development Award; Mentors; Mentorship; Mission; Morbidity - disease rate; Neurobiology; Neuropharmacology; Outcome; Patients; Pattern; Placebo Control; Population; Positioning Attribute; Prefrontal Cortex; Prevalence; Process; Psychiatrist; Public Health; Recruitment Activity; Research; Research Design; Research Personnel; Research Training; Risk; Role; Secure; Selective Serotonin Reuptake Inhibitor; Structure; Suicide attempt; Task Performances; Techniques; Testing; Therapeutic; Time; Training; United States National Institutes of Health; Work; Youth; base; career; cingulate cortex; cohort; experience; in vivo; innovation; neurodevelopment; neuroimaging; neurophysiology; psychopharmacologic; public health relevance; relating to nervous system; response; suicidal risk; symptomatic improvement; treatment response

DESCRIPTION (provided by applicant): Generalized Anxiety Disorder (GAD) is among the most common anxiety disorders in youth, often emerges during adolescence, and is associated with significant morbidity as well as an increased risk of suicide attempts. Importantly, understanding the relationship between psychopharmacologic treatments for pediatric GAD and functional activity and functional connectivity among several anterior limbic structures (e.g., amygdala, ventrolateral prefrontal cortex) may identify biomarkers of treatment response. The present study will combine double-blind, placebo-controlled treatment with the selective serotonin reuptake inhibitor escitalopram and in vivo neuroimaging techniques (i.e., functional MRI and functional connectivity analyses [Fc]) in adolescents with GAD. Additionally, this study will evaluate early, treatment-related changes in functional activity of the ventrolateral prefrontl cortex and the amygdala, as well as the Fc of these structures, to elucidate predictors of treatment response which precede clinical improvement in youth with GAD. The applicant, a board-certified, child and adolescent psychiatrist, will seek to accomplish several goals and objectives over the course of this four year K23 award. In this regard, the long-term goal of this award is to foster the applicant's research career as an independent investigator focusing on the neurophysiology and neuropharmacology of pediatric anxiety disorders. More immediate objectives of this K23 proposal are to: (1) secure training in the neurodevelopment of GAD; (2) develop expertise in fMRI and Fc analyses; (3) become proficient at longitudinal study design, integrating psychopharmacologic interventions and neurophysiology; and (4) enhance the applicant's knowledge of biostatistics. Additional objectives include exploring the neurobiological basis of GAD using a validated fMRI paradigm and Fc analyses with a cohort of GAD patients and healthy subjects, and generating preliminary data regarding treatment-related effects of escitalopram on brain functional activation and Fc patterns in pediatric GAD. The central hypothesis of this proposal is that core dysfunction within the anterior limbic network, which we and others have observed in GAD, will be normalized by successful treatment. Finally, the rationale underlying this hypothesis is that, despite the high prevalence of GAD, there is a need to understand its neurobiology and to identify biomarkers of treatment response and the mechanisms by which SSRIs putatively effect changes in the neurocircuitry of pediatric GAD.

描述(申请人提供)：广泛性焦虑症(GAD)是青少年中最常见的焦虑症之一，通常出现在青春期，与显著的发病率和自杀企图的风险增加有关。重要的是，了解儿童广泛性焦虑症的精神药物治疗与几个前缘结构(如杏仁核、前额叶腹外侧区)之间的功能活动和功能连通性之间的关系，可能会确定治疗反应的生物标志物。目前的研究将结合双盲、安慰剂对照治疗、选择性5-羟色胺再摄取抑制剂艾司匹林和体内神经成像技术(即功能磁共振成像和功能连接分析[FC])来治疗青少年广泛性AD。此外，这项研究将评估与治疗相关的早期腹外侧额叶皮质和杏仁核功能活动的变化，以及这些结构的Fc，以阐明在青少年GAD临床改善之前的治疗反应的预测因素。申请者是一名获得董事会认证的儿童和青少年精神病学家，他将在四年的K23奖项过程中寻求实现几个目标和目的。在这方面，该奖项的长期目标是促进申请者作为一名独立研究员的研究生涯，专注于儿童焦虑症的神经生理学和神经药理学。K23提案更直接的目标是：(1)确保GAD的神经发育方面的培训；(2)发展功能磁共振成像和功能障碍分析方面的专业知识；(3)精通纵向研究设计，整合精神药理学干预和神经生理学；以及(4)增强申请者的生物统计学知识。其他目标包括探索神经生物学 通过对广泛性痴呆症患者和健康受试者进行队列研究，使用经过验证的功能磁共振成像范式和FC分析为广泛性阿尔茨海默病的研究奠定了基础，并生成了有关艾司匹兰对儿童广泛性AD患者脑功能激活和FC模式的治疗相关效应的初步数据。这一建议的中心假设是，我们和其他人在广泛性痴呆症中观察到的前缘网络内的核心功能障碍将通过成功的治疗而正常化。最后，这一假说的基本原理是，尽管广泛性AD的患病率很高，但仍需要了解其神经生物学，并确定治疗反应的生物标志物以及SSRI可能影响儿童广泛性AD神经回路变化的机制。