Trajectories of Brain Maturation among Youth at Risk for Anxiety

有焦虑风险的青少年的大脑成熟轨迹

• 批准号: 9312090
• 负责人: Adriana Galvan
• 金额: $ 68.95万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-05-03 至 2022-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9312090
• 关键词: Address; Adolescence; Adolescent; Affect; Age; Amygdaloid structure; Anxiety; Anxiety Disorders; Automobile Driving; Behavior; Behavioral; Brain; Brain region; Child; Chronic; Communities; Complement; Corpus striatum structure; Decision Making; Development; Evidence based treatment; Evolution; Exhibits; Fright; Functional Magnetic Resonance Imaging; Goals; Heterogeneity; Impairment; Individual; Intervention; Light; Limbic System; Link; Longitudinal prospective study; Measures; Mental Health; Methods; Mission; Modeling; Neurobiology; Outcome; Participant; Patient Self-Report; Pattern; Phenotype; Play; Positioning Attribute; Prefrontal Cortex; Process; Psychophysiology; Regulation; Relapse; Remittance; Research; Rewards; Risk; Risk Behaviors; Risk-Taking; Role; Running; Sampling; Severities; Specific qualifier value; Strategic Planning; Symptoms; System; Systems Development; Testing; Time; United States National Institutes of Health; Ventral Striatum; Work; Youth; anxiety symptoms; anxious; approach avoidance behavior; approach behavior; attentional bias; avoidance behavior; base; causal model; childhood anxiety; cognitive control; coping; curative treatments; design; drinking; effective therapy; functional disability; functional outcomes; innovation; interest; meetings; neural circuit; neuroimaging; neuromechanism; novel; relating to nervous system; response; symptomatology; therapy development

Abstract Anxiety occurs widely among adolescents, with one in three youth meeting criteria for an anxiety disorder before the age of 18. Although evidence-based treatments exist, rates of relapse are strikingly high and treatment does little to alter the chronic, fluctuating course of symptoms. To address these concerns and to achieve the mission of “curative therapeutics” outlined in the current NIH strategic plan, factors linked to heterogeneity in the course of anxiety must be better understood. The goal of this application is to conduct a prospective longitudinal study of youth across the full continuum of anxiety symptoms, characterizing specific neural changes that underlie the evolution of illness and impairment. Existing cross-sectional research has specified a fear circuit encompassing the amygdala (AMY) and ventromedial prefrontal cortex (vmPFC) but has overlooked the role of other potentially important systems (e.g., striatum) in contributing to anxiety. Moreover, this work has failed to address multiple key questions for the field: How does identified circuitry change over time and how does this maturation relate to the course of anxiety symptoms? How do approach and avoidant processes interact and what is the role that the maturing regulatory cortex plays in modulating these limbic- based fear systems and influencing outcomes? In this study, we examine fronto-striato-limbic system development in a community sample (n=120) of youth ages 9-13, selected to exhibit the full range of anxiety symptoms with oversampling at the more severe end of the distribution. We choose this age range in light of robust evidence that it will capture significant worsening of anxiety symptom severity. Subjects will be followed annually for three years to track trajectories of change in approach/avoidance behaviors and the corresponding regulatory circuitry as well as anxiety symptom severity and related functional outcomes. We have a particular interest in tracking divergence from age-expected increases in novelty seeking and risk-taking behavior and its covariation with symptom course. At each time-point, participants will complete risky decision-making tasks while undergoing fMRI along with self-report, behavioral, and psychophysiological measures. These methods are complemented by innovative neuroimaging models that specifically test the direction of influence among target systems, which undergo substantial change in adolescence. Findings from the proposed research will shed light on the component and interactive processes by which approach-, avoidance-, and regulatory- circuitry contribute to the persistence/remittance of anxiety. The result will be a more holistic understanding of the mechanisms underlying heterogeneity in symptom course that may be used to guide the development of targeted interventions.

抽象的 焦虑症在青少年中广泛发生，三分之一的青年遇到焦虑标准 18岁之前的疾病。尽管存在基于证据的治疗，但缓解率惊人 治疗几乎没有改变慢性，波动的症状过程。解决这些问题和 为了实现当前NIH战略计划中概述的“治疗治疗学”的使命，与之相关的因素 在动画过程中的异质性必须更好地理解。该应用的目的是进行 对焦虑症状的全部持续性纵向研究的前瞻性纵向研究，表征特定 神经变化是疾病和损害发展的基础。现有的横断面研究 指定了涉及杏仁核（AMY）和腹侧前额叶皮层（VMPFC）的恐惧电路 忽视了其他潜在重要的系统（例如纹状体）在动画中的作用。而且， 这项工作未能解决该领域的多个关键问题：确定的电路如何随时间变化 这种成熟与动画症状过程有何关系？如何接近和回避 过程相互作用以及成熟调节皮层在调节这些边缘的作用是什么 基于恐惧系统和影响结果？在这项研究中，我们检查了Fronto-Striato-Limbic系统 在9-13岁的青年社区样本（n = 120）中的开发，被选为展示全部动画 在分布更严重的末端过采样的症状。我们选择这个年龄范围 有力的证据表明，它将引起对动画症状严重程度的严重担忧。受试者将遵循 三年再多一次，跟踪进近/避免行为的变化轨迹和相应的 调节电路以及焦虑症状严重程度和相关功能结果。我们有一个特殊的 追踪与年龄预期新颖性和冒险行为的增加的兴趣及其 与症状课程的协变。在每个时间点，参与者将完成风险的决策任务 同时享受fMRI以及自我报告，行为和心理生理措施。这些方法 由创新的神经影像模型完成，这些模型专门测试了影响方向 目标系统，这会发生重大变化。拟议研究的发现将 阐明了组件和互动过程，避免，避免和调节 - 电路有助于动画的持久性/汇款。结果将是对 症状课程中的异质性的基础机制可用于指导发展 有针对性的干预措施。