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: 8932029
• 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/8932029
• 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; Health; High Prevalence; Intervention; Knowledge; Life; Longitudinal Studies; MRI Scans; 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; childhood anxiety; cingulate cortex; cohort; experience; in vivo; innovation; neural correlate; neurodevelopment; neuroimaging; neurophysiology; pediatric patients; psychopharmacologic; 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（由申请人提供）：广泛性焦虑症（GAD）是青少年最常见的焦虑症之一，通常出现在青春期，与显著的发病率以及自杀企图的风险增加有关。重要的是，了解儿童GAD的精神药理学治疗与几个前边缘结构（例如，杏仁核、腹外侧前额叶皮质）可以鉴定治疗反应的生物标志物。本研究将联合收割机双盲、安慰剂对照治疗与选择性5-羟色胺再摄取抑制剂艾司西酞普兰和体内神经成像技术（即，功能性MRI和功能连接分析[Fc]）。此外，本研究将评估腹外侧前额叶皮质和杏仁核功能活动的早期治疗相关变化，以及这些结构的Fc，以阐明GAD青年临床改善之前的治疗反应预测因素。申请人是一名获得委员会认证的儿童和青少年精神病学家，将在这四年的K23奖项中寻求实现几个目标。在这方面，该奖项的长期目标是促进申请人的研究生涯，作为一个独立的研究者，专注于儿童焦虑症的神经生理学和神经药理学。该K23提案的更直接目标是：（1）确保GAD神经发育方面的培训;（2）发展功能磁共振成像和Fc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;（4）增强申请人的生物统计学知识。其他目标包括探索神经生物学 使用经验证的fMRI范例和Fc分析，对一组GAD患者和健康受试者进行GAD的基础研究，并生成关于艾司西酞普兰对儿科GAD患者脑功能激活和Fc模式的治疗相关影响的初步数据。这个建议的中心假设是，我们和其他人在广泛性焦虑症中观察到的前边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，这一假设的基本原理是，尽管广泛性焦虑症的患病率很高，但仍有必要了解其神经生物学，并确定治疗反应的生物标志物和SSRI类药物对儿童广泛性焦虑症神经回路产生影响的机制。