Puberty-related development of fronto-amygdala circuitry in anxious youth: A multimodal neuroimaging study with ultra-high resolution MRI scanner (7T) - Supplement

焦虑青年中与青春期相关的额杏仁核回路的发育：使用超高分辨率 MRI 扫描仪 (7T) 进行的多模式神经影像研究 - 补充

• 批准号: 10815888
• 负责人: Cecile D. Ladouceur
• 金额: $ 13.85万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-08-01 至 2024-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10815888
• 关键词: Adolescence; Adolescent; Adult; Age; Amygdaloid structure; Anxiety; Anxiety Disorders; Area; Award; Behavioral; Benchmarking; Brain; COVID-19 pandemic; Clinical; Data; Data Analytics; Development; Diagnostic; Emergency Situation; Ensure; Faculty; Fellowship; Functional Magnetic Resonance Imaging; Future; Gender; Goals; Incidence; Intervention; Magnetic Resonance Imaging; Mentored Patient-Oriented Research Career Development Award; Mentorship; Minor; Neurobiology; Neuronal Plasticity; Parents; Pathologic; Physicians; Positioning Attribute; Postdoctoral Fellow; Prevalence; Psychopathology; Puberty; Public Health; Publishing; Research Activity; Research Personnel; Research Support; Resources; Scientist; Supervision; Thinking; Time; Training; Treatment Efficacy; Universities; Youth; anxiety symptoms; anxious; childhood anxiety; cognitive control; depressive symptoms; early adolescence; emotion regulation; experience; girls; health organization; improved; interest; lens; multimodal neuroimaging; neurodevelopment; neuroimaging; neuromechanism; pediatric emergency; pilot test; public health emergency; resilience; resilience factor; rumination; skills; symposium; symptomatology; trend; ultra high resolution

Abstract Pediatric anxiety disorders are an area of critical public health need. The past two decades have seen substantial increases in both incidence and prevalence of anxiety psychopathology,1,2 trends which were amplified by the COVID-19 epidemic and have recently been declared an emergency.3 Early adolescence and the emergence of puberty is a pivotal moment wherein trajectories of anxiety symptoms begin to rise, especially in girls.4,5 It is also a period of puberty-associated neuroplastic changes in brain networks associated with emotion regulation and cognitive control.6,7 The parent R01 for this supplement investigates these puberty-related neurodevelopmental mechanisms through the lens of an important brain circuit, vmPFC-amygdala connectivity, and its relationship to threat reactivity, a known factor in anxiety disorders.8–10 This project proposes to extend the aims of the parent R01 to another known factor, perseverative thought (PT), a transdiagnostic construct comprising negative, repetitive thinking. PT in the form of worry and rumination has been associated with anxiety for decades.11 Although PT can vary in different aspects, a hallmark of pathological PT is its uncontrollability.12–14 Thus, the ability to disengage from PT is a potential factor of resilience. Recent years have seen interest in interventions targeting PT, which enhance PT disengagement skills and appear effective against anxiety and depressive symptoms.15 However, the neural mechanisms of real-time disengagement from PT in adolescence remain unknown. The study of neurodevelopmental mechanisms of PT disengagement therefore has substantial potential to improve treatment efficacy and identify new neurobiologically-informed treatment targets. The aim of the proposed project is to initiate a developmental study of PT disengagement by adapting a paradigm previously published in adults16 for use in adolescents. Aim 1 proposes minor adaptations of the task and behavioral pilot testing (N=30) to ensure understandability and tolerability in adolescents, then extending to a neuroimaging context (N=30) to confirm its tolerability. Aim 2 proposes analyses of the pilot data and their relationship to gender and symptomatology. The Candidate will expand her extant fMRI data analytic skills through a training plan including formal didactics and supervision from the study PI. This project will benefit from the parent PI’s extensive experience in neurodevelopment and psychopathology and the wealth of mentorship and resources at the University of Pittsburgh. It will further the Candidate’s goals of becoming an independent investigator by supporting research activities during the final year of clinical fellowship and generating pilot data and testable hypotheses for a K23 award proposal. Benchmarks for this award include presentations at scientific conferences and transition to a T32 postdoctoral fellowship as the next steps towards a faculty position and independence as a physician-scientist.

摘要 儿科焦虑症是一个关键的公共卫生需求领域。在过去的二十年里， 焦虑精神病理学的发病率和患病率均显著增加，1，2趋势， 2019冠状病毒病疫情加剧了这一问题，最近已被宣布为紧急情况。 青春期的出现是焦虑症状的轨迹开始上升的关键时刻， 特别是在女孩中。4，5这也是一个与青春期相关的大脑网络中的神经可塑性变化相关的时期。 情绪调节和认知控制。6，7 该补充剂的母体R 01研究了这些青春期相关的神经发育机制 通过一个重要的大脑回路的透镜，vmPFC-杏仁核连接，及其与威胁的关系， 反应性，焦虑症的一个已知因素。8 -10本项目建议将父母R 01的目标扩展到 另一个已知的因素，持续性思维（PT），一种包含负的、重复的、 思维几十年来，以担心和沉思形式出现的PT一直与焦虑有关。 病理性PT的一个特点是其不可降解性。12 -14因此， 脱离PT是恢复力的一个潜在因素。近年来，人们对干预措施感兴趣， PT，它增强了PT脱离技能，对焦虑和抑郁症有效。 然而，在青春期实时脱离PT的神经机制仍然未知。的 因此，PT脱离的神经发育机制的研究具有改善 治疗效果，并确定新的神经生物学告知治疗目标。 建议项目的目的是通过调整一个 paradigm先前在成人中发表的16用于青少年。目标1建议对任务进行小的调整 和行为试点测试（N=30），以确保青少年的可理解性和耐受性，然后扩展 神经影像学背景（N=30），以确认其耐受性。目标2提出了对试点数据及其 与性别和生殖学的关系。候选人将扩大她现有的功能磁共振成像数据分析技能 通过培训计划，包括正式教学和研究PI的监督。 该项目将受益于父母PI在神经发育方面的丰富经验， 精神病理学和匹兹堡大学丰富的导师和资源。中国将继续坚持 候选人的目标是通过在期末考试期间支持研究活动，成为一名独立的研究者。 一年的临床研究金并为K23奖项提案生成试点数据和可测试的假设。 该奖项的基准包括在科学会议上的演讲和过渡到T32博士后 奖学金作为下一步走向教师的立场和独立作为一个物理学家，科学家。