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: 9325579
• 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 2019-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9325579
• 关键词: Adolescence; Adolescent; Affect; Amygdaloid structure; Anterior; Antidepressive Agents; Anxiety; Anxiety Disorders; Award; Biological Markers; Biometry; Brain; Brain imaging; 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; 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; Psychiatrist; Public Health; Recruitment Activity; Research; Research Design; Research Personnel; Role; Scanning; Secure; Selective Serotonin Reuptake Inhibitor; Structure; Suicide attempt; Task Performances; Techniques; Testing; Time; Training; United States National Institutes of Health; Work; Youth; career; childhood anxiety; cingulate cortex; cohort; experience; imaging study; in vivo; innovation; neural correlate; neurodevelopment; neuroimaging; neurophysiology; neuropsychopharmacology; pediatric patients; predictive of treatment response; psychopharmacologic; public health relevance; response biomarker; standard of care; 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）是青少年中最常见的焦虑症之一，通常在青春期出现，与显着的发病率以及自杀企图风险增加相关。重要的是，了解儿科广泛性焦虑症的精神药物治疗与功能活动以及几种前缘结构（例如杏仁核、腹外侧前额叶皮层）之间的功能连接之间的关系可以确定治疗反应的生物标志物。本研究将双盲、安慰剂对照治疗与选择性血清素再摄取抑制剂艾司西酞普兰和体内神经影像技术（即功能性 MRI 和功能连接分析 [Fc]）结合起来，治疗 GAD 青少年。此外，这项研究将评估腹外侧前额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，以阐明治疗反应的预测因素，这些反应在患有广泛性焦虑症的青少年临床改善之前。申请人是一名经过委员会认证的儿童和青少年精神病学家，将寻求在为期四年的 K23 奖项的过程中实现多个目标。在这方面，该奖项的长期目标是培养申请人作为独立研究者的研究生涯，专注于儿科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) 确保广泛性焦虑症神经发育的培训； (2) 发展 fMRI 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 使用经过验证的功能磁共振成像范式和对一组 GAD 患者和健康受试者进行 Fc 分析，得出 GAD 的基础，并生成有关艾司西酞普兰对儿科 GAD 脑功能激活和 Fc 模式的治疗相关影响的初步数据。该提议的中心假设是，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恢复正常。最后，这一假设的基本原理是，尽管 GAD 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 SSRIs 影响儿科 GAD 神经回路变化的机制。

项目成果

Neural Function Before and After Mindfulness-Based Cognitive Therapy in Anxious Adolescents at Risk for Developing Bipolar Disorder.

对有患双相情感障碍风险的焦虑青少年进行正念认知治疗前后的神经功能。

• DOI: 10.1089/cap.2015.0054
• 发表时间: 2016
• 期刊: Journal of child and adolescent psychopharmacology
• 影响因子: 1.9
• 作者: Strawn,JeffreyR;Cotton,Sian;Luberto,ChristinaM;Patino,LRodrigo;Stahl,LaurenA;Weber,WadeA;Eliassen,JamesC;Sears,Richard;DelBello,MelissaP
• 通讯作者: DelBello,MelissaP

The Impact of Antidepressant Dose and Class on Treatment Response in Pediatric Anxiety Disorders: A Meta-Analysis.

• DOI: 10.1016/j.jaac.2018.01.015
• 发表时间: 2018-04
• 期刊: Journal of the American Academy of Child and Adolescent Psychiatry
• 影响因子: 13.3
• 作者: Strawn JR;Mills JA;Sauley BA;Welge JA
• 通讯作者: Welge JA

Pharmacotherapy for Pediatric Generalized Anxiety Disorder: A Systematic Evaluation of Efficacy, Safety and Tolerability.

• DOI: 10.1007/s40272-015-0153-1
• 发表时间: 2016-02
• 期刊: Paediatric drugs
• 作者: Dobson ET;Strawn JR
• 通讯作者: Strawn JR

Pharmacologic Treatment of Pediatric Anxiety Disorders.

• DOI: 10.1007/s40501-016-0076-7
• 发表时间: 2016-06
• 期刊: Current treatment options in psychiatry

Executive Functioning in Pediatric Anxiety and Its Relationship to Selective Serotonin Reuptake Inhibitor Treatment Response: A Double-Blind, Placebo-Controlled Trial.

小儿焦虑症的执行功能及其与选择性血清素再摄取抑制剂治疗反应的关系：双盲、安慰剂对照试验。

• DOI: 10.1089/cap.2022.0012
• 发表时间: 2022
• 期刊: Journal of child and adolescent psychopharmacology
• 影响因子: 1.9
• 作者: Baumel,WThomas;Mills,JeffreyA;Schroeder,HeidiK;Specht,AshleyM;Rothenberg,Richard;Peris,TaraS;Strawn,JeffreyR
• 通讯作者: Strawn,JeffreyR