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）：儿童焦虑症很普遍，并且越来越被认为是一个主要的公共卫生问题。除了与儿童焦虑症相关的心理痛苦和残疾之外，这些症状通常还与共病抑郁症状相关，加剧其他疾病，并增加以后患焦虑症、抑郁症以及共病吸毒和酗酒的风险。尽管广泛性焦虑症（GAD）在儿童时期发生很重要，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通过识别与人类早期广泛性焦虑症相关的中间大脑表型，以我们在年轻非人类灵长类动物中的工作为基础。前额叶-杏仁核连接性改变和杏仁核计时改变与广泛性焦虑症症状相关的假设将通过结构和功能 MRI 结合相关的生理和行为测量进行评估。虽然这些方法在成人中常用，在青少年中使用较少，但很少有研究检验这些措施与青春期前儿童临床上显着焦虑的关系。这一点尤其重要，因为成人和青少年的焦虑和抑郁通常在生命早期就开始表现为临床上显着的焦虑。了解青春期前儿童 GAD 表达背后的神经回路变化将为使用旨在早期检测的生物标志物提供依据。具体来说，这些数据将为前瞻性纵向研究奠定基础，研究评估杏仁核计时和前额叶-杏仁核连接性与这些儿童疾病的早期发现和治疗相关的效用。该提案旨在为初始阶段提供资金 这项研究的长期计划是获得非常大的广泛性焦虑症儿童样本。由于共病症状的异质性，获得大样本将使我们能够解析与不同的潜在神经改变相关的广泛性焦虑症和相关症状。这有可能为当前广泛性焦虑症的概念提供新的见解，并将为临床上显着焦虑的儿童症状模式的基于大脑的新分类奠定基础。在广泛性焦虑症儿童中进行这些研究的机会很多。他们将为理解与精神病理学最早表达相关的大脑回路的结构和功能提供一个发展框架。此外，这些知识可能为针对相关神经回路的关键组成部分并考虑发育中儿童大脑的可塑性的社会心理和药物干预措施的发展提供理论基础。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。