Brain Mechanisms Underlying Childhood Generalized Anxiety Disorder

童年广泛性焦虑症的大脑机制

• 批准号: 8460804
• 负责人: Ned H Kalin
• 金额: $ 21.67万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-04-19 至 2015-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8460804
• 关键词: Accounting; Acute; Adolescent; Adult; Affect; Alcohol abuse; Amygdaloid structure; Anisotropy; Anxiety; Anxiety Disorders; Arousal; Base of the Brain; Biological Markers; Brain; Child; Childhood; Chronic; Chronic Disease; Classification; Coupling; Cues; Data; Development; Down-Regulation; Drug abuse; Early Diagnosis; Early treatment; Face; Foundations; Functional Magnetic Resonance Imaging; Functional disorder; Funding; Future; Generalized Anxiety Disorder; Heterogeneity; Human; Hyperactive behavior; Image; Individual; Intervention; Knowledge; Life; Link; Longitudinal Studies; Measures; Mediating; Medical; Mental Depression; Methods; Monkeys; Muscle; Nucleic Acid Regulatory Sequences; Onset of illness; Pattern; Phenotype; Physiological; Population Study; Prevention; Protocols documentation; Psychopathology; Public Health; Reaction; Recovery; Regulation; Research; Risk; Risk Factors; Sampling; Site; Staging; Stimulus; Stress; Stressful Event; Structure; Substance abuse problem; Symptoms; Testing; Translating; Work; base; behavior measurement; childhood anxiety; clinically significant; depressive symptoms; design; disability; early childhood; effective intervention; improved; insight; neural circuit; nonhuman primate; novel; novel strategies; prospective; psychologic; psychosocial development; relating to nervous system; response; sound

DESCRIPTION (provided by applicant): Anxiety disorders in children are prevalent and are increasingly recognized as a major public health concern. In addition to the psychological suffering and disability associated with childhood anxiety disorders, these symptoms are commonly associated with comorbid depressive symptoms, exacerbate other medical illnesses, and increase the later risk to develop anxiety disorders, depression and comorbid drug and alcohol abuse. Despite the importance of generalized anxiety disorder (GAD) occurring during childhood, little is known about the brain alterations that mediate its development and pathophysiology. The overall aim of this proposal is to build on our work in young nonhuman primates by identifying intermediate brain phenotypes that are linked to early human childhood GAD. The hypothesis that altered prefrontal-amygdala connectivity and altered amygdala chronometry is associated with symptoms of GAD will be evaluated with structural and functional MRI, in conjunction with relevant physiological and behavioral measures. While these methods have been commonly used in adults and less frequently in adolescents, very few studies have examined these measures in relation to clinically significant anxiety in pre-adolescent children. This is particularly important since anxiety and depression in adults and adolescents frequently begins as clinically significant anxiety earlier in life. Understanding alterations in the neural circuitry that underlie the expression of GAD in preadolescent children will provide a rationale for using biomarkers aimed at early detection. Specifically, these data will lay the foundation for prospective longitudinal studies examining the utility of assessing amygdala chronometry and prefrontal-amygdala connectivity in relation to the early detection and treatment of these childhood illnesses. This proposal is intended to fund the initial stages of this research with the long-term plan to obtain a very large sample of children with GAD. Because of the heterogeneity of comorbid symptoms, obtaining a large sample will allow us to parse GAD and associated symptoms in relation to distinct underlying neural alterations. This has the potential to provide new insight into the current conceptualization of GAD and will set the stage for novel brain based classification of symptom patterns in children with clinically significant anxiety. The opportunities from performing these studies in GAD children are numerous. They will provide a developmental framework for understanding the structure and function of brain circuits that are associated with the earliest expression of psychopathology. In addition, this knowledge may provide a rationale 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 tha are based on a sound neurodevelopmental rationale hold the promise for the prevention of later adolescent and adult anxiety, depression and substance abuse.

描述（由申请人提供）：儿童的焦虑症普遍存在，并越来越被认为是主要的公共卫生问题。除了与儿童焦虑症相关的心理痛苦和残疾之外，这些症状通常与合并症抑郁症状有关，加剧其他医学疾病，并增加患焦虑症，抑郁症，抑郁症和合并症的药物和酒精滥用的风险。尽管童年时期发生普遍焦虑症（GAD）的重要性，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通过确定与早期人类儿童时期有关的中间脑表型来建立我们在年轻的非人类灵长类动物中的工作。与相关的生理和行为指标结合使用，将通过结构和功能性MRI评估改变前额叶 - 杏仁核连通性和改变的杏仁核症状的假设与GAD症状有关。尽管这些方法通常是在成年人中使用的，而在青少年中却较少使用，但很少有研究检查了这些措施与青春期前儿童中临床上显着的焦虑有关。这一点尤其重要，因为成人和青少年的焦虑和抑郁症经常以临床上显着的焦虑开始。理解在前儿童中GAD表达的神经回路中的改变将为使用针对早期检测的生物标志物提供理由。具体而言，这些数据将为前瞻性纵向研究奠定基础，研究了与早期发现和治疗这些童年疾病有关的评估杏仁核等级和前额叶 - 杏仁核连接性的实用性。该建议旨在为 这项研究的长期计划是为了获得大量患有GAD的儿童样本。由于合并症症状的异质性，获得大型样本将使我们能够与不同的潜在神经改变有关的GAD和相关症状。这有可能提供对当前GAD概念化的新见解，并将为具有临床意义焦虑的儿童的新型脑部症状模式分类奠定了基础。在GAD儿童中进行这些研究的机会很多。他们将提供一个发展框架，以了解与心理病理学最早表达相关的脑电路的结构和功能。此外，这些知识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提供了理由，并考虑了发育中儿童大脑的可塑性。早期更有效的干预措施是基于合理的神经发育原理，有望预防后来的青少年和成人焦虑，抑郁和药物滥用。