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）：儿童焦虑症（AD）很常见，并且越来越被认为是一个主要的公共卫生问题。除了与儿童 AD 相关的心理痛苦和残疾之外，儿童时期的焦虑也是日后焦虑症、抑郁症和药物滥用的重要危险因素。尽管儿童焦虑症普遍存在并产生影响，但人们对介导其发展和病理生理学的大脑变化知之甚少。该提案的总体目标是确定与幼儿（8-12 岁）AD 症状相关的中间大脑表型。这些研究将使用结构和功能磁共振成像来检验这样的假设：在经历轻度社会威胁的不同阶段，前额叶-杏仁核连接的改变和杏仁核反应的过度与焦虑症状有关。虽然这些方法在成人中常用，在青少年中使用较少，但针对青春期前焦虑儿童进行的神经影像学研究却很少。更好地了解焦虑症状的发展可能会为早期诊断和干预创造机会，以减少甚至预防未来的精神病理学。了解青春期前儿童 AD 表达背后的神经回路的变化将为使用旨在早期检测的生物标志物提供基本原理，并为了解与精神病理学最早表达相关的大脑回路的完整性提供一个发展框架。这些知识也可能为社会心理和药物干预措施的发展奠定基础，这些干预措施针对相关神经回路的关键组成部分，并考虑到发育中儿童大脑的可塑性。基于合理的神经发育原理的早期、更有效的干预措施有望预防以后的青少年和成人焦虑、抑郁和药物滥用。这些数据还将为前瞻性纵向研究奠定基础，研究评估杏仁核功能和前额叶-杏仁核连接对于早期发现和治疗儿童焦虑的效用。拟议的项目具有很高的科学影响力，并为威廉姆斯博士提供了一个独特的机会来扩展她的培训 精神神经影像学包括对儿科焦虑症患者的研究，并学习功能和结构连接方法来评估儿童 AD 中杏仁核网络的完整性。专门的临床培训将增强威廉姆斯博士的实验背景，使她能够更好地开展临床应用研究。 F32 期间收集的数据将用于计划提交的 R01 项目，该项目用于儿童 AD 的大型多站点成像研究（威廉姆斯博士将担任该研究的联合 PI）以及独立的 K01 申请。从事这个令人兴奋的转化项目，在所产生的出版物中担任第一作者，并在校外资助申请中担任首席研究员，将有助于威廉姆斯博士过渡到独立研究职位。