Brain Mechanisms of Childhood Anxiety Disorders

儿童焦虑症的大脑机制

• 批准号: 8782739
• 负责人: Lisa Williams
• 金额: $ 5.89万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-09-01 至 2017-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8782739
• 关键词: Accounting; Acute; Admixture; Adolescence; Adolescent; Adult; Affect; Age; Amygdaloid structure; Anisotropy; Anterior; Anxiety; Anxiety Disorders; Association Learning; Base of the Brain; Biological Markers; Biological Neural Networks; Brain; Categories; Child; Childhood; Clinical; Cues; Data; Detection; Development; Diagnosis; Diagnostic; Diffusion Magnetic Resonance Imaging; Early Diagnosis; Early Intervention; Early treatment; Emotional; Emotions; Etiology; Extramural Activities; Face; Family; Foundations; Fright; Functional Magnetic Resonance Imaging; Functional disorder; Funding; Future; Image; Individual; Insula of Reil; Intervention; Knowledge; Learning; Life; Link; Longitudinal Studies; Measures; Mediating; Mental Depression; Mental Health; Methods; Parents; Patients; Pattern; Phase; Phenotype; Positioning Attribute; Prefrontal Cortex; Prevalence; Prevention; Psychopathology; Public Health; Recovery; Regression Analysis; Regulation; Research; Research Personnel; Rest; Risk; Risk Factors; Role; Scanning; Seeds; Series; Signal Transduction; Site; Staging; Stimulus; Substance abuse problem; Symptoms; Temperament; Testing; Time; Training; Uncertainty; Work; base; childhood anxiety; cingulate cortex; clinical application; design; disability; disorder control; effective intervention; emotion regulation; emotional reaction; experience; insight; neural circuit; neuroimaging; nonhuman primate; novel; prevent; prospective; psychologic; psychosocial development; public health relevance; relating to nervous system; response; social; sound; white matter

DESCRIPTION (provided by applicant): Anxiety disorders (ADs) in children are common and increasingly recognized as a major public health concern. In addition to the psychological suffering and disability associated with childhood ADs, anxiety during childhood is a significant risk factor for anxiety disorders, depression and substance abuse later in life. Despite the prevalence and impact of childhood anxiety, little is known about the brain alterations that mediate its development and pathophysiology. The overall aim of this proposal is to identify intermediate brain phenotypes that are linked to AD symptoms in young children (age 8-12). Using structural and functional magnetic resonance imaging, these studies will test the hypothesis that altered prefrontal-amygdala connectivity and exaggerated amygdala response during different phases of experiencing a mild social threat are associated with the symptoms of anxiety. While these methods have been commonly used in adults and less frequently in adolescents, very few neuroimaging studies have been conducted with preadolescent children with anxiety. A better understanding of anxiety symptoms as they develop may create opportunities for early diagnosis and intervention to reduce or even prevent future psychopathology. Understanding alterations in the neural circuitry that underlies the expression of ADs in preadolescent children will provide a rationale for using biomarkers aimed at early detection, as well as a developmental framework to understand the integrity of brain circuits associated with the earliest expressions of psychopathology. This knowledge may also set the stage for the development of psychosocial and pharmacologic interventions that target key components of the involved neural circuit and take into account the plasticity of the developing child's brain. Early, more effective interventions that are based on a sound neurodevelopmental rationale hold the promise for the prevention of later adolescent and adult anxiety, depression and substance abuse. These data will also lay the foundation for prospective longitudinal studies examining the utility of assessing amygdala function and prefrontal-amygdala connectivity for early detection and treatment of childhood anxiety. The proposed projects are of high scientific impact, and provide a unique opportunity for Dr. Williams to expand her training in psychiatric neuroimaging to include studies of pediatric anxiety patients and to learn functional and structural connectivity methods to evaluate the integrity of amygdala networks in childhood ADs. Dedicated clinical training will enhance Dr. Williams' experimental background, making her better equipped to conduct research with clinical applications. Data collected during the F32 period will be used for a planned R01 submission for a large, multi-site imaging study of childhood ADs, on which Dr. Williams will be a co-PI, and an independent K01 application. Working on this exciting translational project, taking a first- author role on resulting publicatios, and assuming a PI role on applications for extramural funding will facilitate Dr. Williams' transition to an independent research position.

描述（由申请人提供）：儿童中的焦虑症（AD）很普遍，并且越来越被认为是主要的公共卫生问题。除了与儿童期广告相关的心理痛苦和残疾之外，儿童期焦虑是焦虑症，抑郁症和滥用药物的重要危险因素。尽管儿童焦虑症的流行和影响，但对介导其发育和病理生理学的大脑改变知之甚少。该提案的总体目的是确定与幼儿AD症状有关的中间脑表型（8-12岁）。这些研究使用结构和功能性磁共振成像，将检验以下假设，即在经历轻微的社会威胁的不同阶段，改变了前额叶 - 杏仁核连接性和夸张的杏仁核反应，与焦虑症状有关。尽管这些方法通常用于成年人，而在青少年中却较少使用，但很少对焦虑症的前儿童进行神经影像学研究。更好地了解焦虑症状时，可能会为早期诊断和干预措施创造机会，以减少甚至预防将来的心理病理学。理解基于在前儿童中AD表达的神经回路的改变将为使用旨在早期检测的生物标志物以及一个发展框架，以了解与最早的精神病理学表达相关的脑回路的完整性。这些知识还可能为发展涉及神经回路的关键组成部分的心理和药理干预措施的发展奠定了基础，并考虑了发育中的儿童大脑的可塑性。早期，基于合理的神经发育原理的更有效的干预措施有望预防后来的青少年和成人焦虑，抑郁症和药物滥用。这些数据还将为前瞻性纵向研究奠定基础，以研究评估杏仁核功能和前额叶 - 杏仁核连接性的实用性，以早期检测和治疗儿童焦虑症。拟议的项目具有很高的科学影响，并为威廉姆斯博士提供了一个独特的机会，以扩大她的培训 精神病神经影像学包括对小儿焦虑患者的研究以及学习功能和结构连通方法，以评估杏仁核网络在儿童期广告中的完整性。专门的临床培训将增强威廉姆斯博士的实验背景，使她能够更好地通过临床应用进行研究。在F32期间收集的数据将用于计划的R01提交，用于对童年广告进行的大型多站点成像研究，威廉姆斯博士将在其上是Co-Pi和独立的K01应用。从事这个令人兴奋的翻译项目，在产生的Publicatios中担任第一作者角色，并在校外资金的申请中发挥PI角色，将有助于威廉姆斯博士过渡到独立的研究职位。