Emergence, stability, and predictors of anxiety in Fragile X syndrome

项目总结/摘要 焦虑是最常见的儿科心理健康问题，影响约10%的儿童和成人1。 鉴于焦虑的普遍性和影响，最近的兴趣集中在表征焦虑上 在高焦虑风险临床亚组（例如，神经发育障碍），以提供关键的洞察力， 具体的风险因素，发展途径和焦虑的后果。脆性X的个体 综合征（FXS）构成了这样一个高焦虑风险亚组，高达80%的青少年和成人 符合至少一种焦虑症的标准16.我们最初由NIMH资助的R 01的工作表明， 在FXS中，焦虑出现在儿童早期，39%的学龄前儿童被诊断出至少有一种焦虑 疾病17，并在整个幼儿期的严重程度增加。本R 01的第一个供资期（2016-2023年） 在描述焦虑的出现、稳定性和流行性方面非常成功（至今有26篇论文） 在FXS儿童中纵向跨越幼儿期（3、4和5-7岁），与FXS儿童相比， 特发性（即，非综合征型）自闭症谱系障碍（nsASD）和神经型（NT）儿童。但是，在这方面， 这项工作引发了一系列关于焦虑症状发展轨迹的新问题， 从早期到中期的FXS诊断，这对确定稳定性和后果至关重要 FXS中的焦虑在关键的早期发展阶段，当干预是最有效的。 为了解决这些差距，这一具有竞争力的续约应用程序将利用我们现有的、丰富的、多维度的 纵向数据集，并遵循我们现有的FXS儿童、nsASD儿童和NT儿童队列 通过8-10年，以及招募一个新的大的8至10岁的横截面队列。具体 目的是（1）确定FXS中3-10岁的焦虑症状和诊断的变化 与nsASD儿童和NT儿童相比;（2）记录潜在早期风险的程度 FXS儿童与非FXS儿童相比， nsASD和NT儿童;和（3）确定（a）焦虑症状和诊断率，（B）功能 与焦虑相关的损伤，以及（c）与FXS儿童相比， nsASD和NT儿童在童年中期。这项研究是创新的，它包括一个智商匹配的 nsASD对照组，将回答关于综合征特异性的关键问题，并通过以下方式扩大我们的影响： 了解nsASD儿童焦虑的发展、预测因素和后果 和智力残疾。这项工作的意义在于它将大大扩展我们对焦虑的理解， FXS通过提供有关发展过程，预测因素和后果的关键信息， 儿童焦虑，这将告知干预的时机和目标，这将改善儿童的生活质量。 患有FXS的儿童及其家人。

PROJECT SUMMARY/ABSTRACT Anxiety is the most common pediatric mental health problem, affecting ~10% of children and adolescents1. Given the substantial prevalence and impact of anxiety, recent interest has focused on characterizing anxiety within high-anxiety-risk clinical subgroups (e.g., neurodevelopmental disorders) to provide critical insight into the specific risk factors, developmental pathways, and consequences of anxiety. Individuals with fragile X syndrome (FXS) constitute one such high-anxiety-risk subgroup, with up to ~80% of adolescents and adults meeting criteria for at least one anxiety disorder16. Work from our initial NIMH-funded R01 demonstrated that anxiety emerges early in childhood in FXS, with 39% of preschoolers diagnosed with at least one anxiety disorder17, and increases in severity across early childhood. The first funding period of this R01 (2016-2023) was highly successful (26 papers to date) in characterizing the emergence, stability, and prevalence of anxiety longitudinally across early childhood (3, 4, and 5-7 years) in children with FXS contrasted to children with idiopathic (i.e., non-syndromic) autism spectrum disorder (nsASD) and neurotypical (NT) children. However, this work has fueled a new set of questions regarding the developmental trajectory of anxiety symptoms and diagnoses from early to middle childhood in FXS which are crucial to identifying the stability and consequences of anxiety in FXS across critical early developmental periods when intervention is known to be most effective. To address these gaps, this competitive renewal application will leverage our existing, rich, multidimensional longitudinal dataset and follow our existing cohort of children with FXS, children with nsASD, and NT children through 8-10 years, as well as recruit a new large cross-sectional cohort of 8-to-10-year-olds. The specific aims are to (1) Determine change in anxiety symptoms and diagnoses from 3-10 years of age in FXS contrasted to children with nsASD and NT children; (2) Document the extent to which potential early risk factors predict change in anxiety symptoms and diagnoses in children with FXS contrasted to children with nsASD and NT children; and (3) Identify (a) rates of anxiety symptoms and diagnoses, (b) functional impairment associated with anxiety, and (c) sex differences in children with FXS contrasted to children with nsASD and NT children during middle childhood. This study is innovative in its inclusion of an IQ-matched nsASD contrast group, which will answer critical questions on syndrome specificity and amplify our impact by generating knowledge on the development, predictors, and consequences of anxiety in children with nsASD and intellectual disability. This work is significant in that it will greatly expand our understanding of anxiety in FXS by providing critical information about the developmental course, predictors, and consequences of childhood anxiety, which will inform the timing and targets of intervention that will improve quality of life for children with FXS and their families.