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

摘要 儿童焦虑症是一个严重的公共卫生需求领域。在过去的二十年里，我们看到了 焦虑精神病的发病率和流行率都大幅增加，1，2趋势是 被新冠肺炎疫情放大，最近被宣布为紧急情况。3青春期早期和 青春期的出现是焦虑症状轨迹开始上升的关键时刻， 尤其是女孩。4、5也是青春期相关脑神经可塑性改变的相关脑部网络 与情绪调节和认知控制有关 本补充材料的父母R01研究了这些与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-杏仁核的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R01的目标扩展到 另一个已知的因素是持之以恒的思维(PT)，这是一种跨诊断结构，由消极的、重复的 思考。几十年来，焦虑和沉思的PT一直与焦虑联系在一起。11尽管PT 可以在不同的方面有所不同，病理性PT的一个标志是它的不可控性。12-14因此， 脱离PT是恢复能力的一个潜在因素。近年来，人们对针对以下目标的干预感兴趣 PT，提高PT脱离技能，对焦虑和抑郁症状似乎有效。15 然而，青春期实时脱离PT的神经机制仍不清楚。这个 因此，对PT脱离的神经发育机制的研究具有很大的潜力。 治疗效果，并确定新的神经生物学知情的治疗目标。 拟议项目的目的是启动一项关于PT脱离的发展研究，方法是使 先前在成年时发表的范例16，供青少年使用。目标1建议对任务进行较小的调整 和行为试点测试(N=30)，以确保青少年的理解和耐受性，然后扩大 神经影像检查(N=30)以确认其耐受性。目标2建议分析试点数据及其 与性别和症状学的关系。应聘者将扩展她现有的fMRI数据分析技能 通过培训计划，包括正式的教学和来自学习PI的监督。 该项目将受益于家长PI在神经发育和 精神病理学和匹兹堡大学丰富的导师和资源。它将进一步推动 候选人通过支持期末考试期间的研究活动成为独立调查员的目标 一年的临床团契，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向T32博士后的过渡 团契是迈向教员地位和作为内科科学家的独立性的下一步。

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.