Autonomic and Sensory Dysfunctions in FMR1 Conditions: Development, Mechanisms and Consequences

FMR1 条件下的自主神经和感觉功能障碍：发展、机制和后果

• 批准号: 10390007
• 负责人: Jane E Roberts
• 金额: $ 67.22万
• 依托单位: UNIVERSITY OF SOUTH CAROLINA AT COLUMBIA
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-07-08 至 2027-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10390007
• 关键词: Adaptive Behaviors; Address; Adult; Affect; Age; Anxiety; Arousal; Autonomic nervous system; Behavior; Behavioral; Biological; CGG repeat; Child; Data; Development; FMR1; FMR1 Premutation; FMRP; Female; Fragile X Premutation; Fragile X Syndrome; Functional disorder; Genetic; Genetic Variation; Heart Rate; Impairment; Individual; Infant; Inherited; Intervention; Knowledge; Learning; Length; Life; Link; Measures; Messenger RNA; Molecular Genetics; Mutation; Outcome; Pathway interactions; Phenotype; Physiological; Research; Risk; Role; Sensory; Severities; Sinus Arrhythmia; Symptoms; Time; Work; autism spectrum disorder; experience; heart function; improved; indexing; infancy; interest; male; prospective; reduce symptoms; respiratory; response; sensory stimulus; skills; social communication

PROJECT SUMMARY/ABSTRACT Despite the impairment in fragile X syndrome (FXS) and the fragile X premutation (FXpm), surprisingly little research has examined the underpinnings of these impairments. One potential factor that contributes to impairment is autonomic nervous system (ANS) dysfunction. Elevated physiological arousal, reflecting ANS dysfunction, has long been implicated as contributing to learning impairments and atypical behavior in FXS. While ANS dysfunction has been linked to impairment in both FXS and FXpm, research has not examined the presence, onset, developmental trajectory, or developmental consequences of ANS dysfunction or how molecular-genetic factors are associated. This project addresses these critical gaps with the following specific aims: (1) Identify the onset and developmental trajectory of baseline ANS dysfunction through prospective longitudinal assessment at 6, 9, 12, and 24 months in FXS (n=30 males) and FXpm (n=30; 15 males and 15 females) contrasted to typical controls (n=45; 30 males and 15 females); (2) Determine how molecular-genetic variation relates to the onset and/or developmental trajectory of ANS dysfunction in FXS and FXpm; (3) Characterize behavioral and ANS reactivity to sensory stimuli through prospective longitudinal assessment at 6, 9, 12, and 24 months in FXS and FXpm; and (4) Document the consequences of ANS dysfunction across infancy on sensory processing impairments, adaptive skills, ASD symptoms, and social communication, concurrently and at 24 months in FXS and FXpm. This work will have tremendous impact by greatly expanding information on the mechanistic underpinnings, biological pathways, and timing of symptom progression, which is essential to identify targets and timing of treatment to reduce symptom severity in FXS and FXpm. Our focus on infancy is critical, as evidence has documented that intervention provided early in life has the potential to accelerate development and improve developmental trajectories over time in a multi-dimensional manner.

项目摘要/摘要 尽管脆弱的X综合征（FXS）和脆弱的X Premunt（FXPM）受损，但令人惊讶的很少 研究检查了这些障碍的基础。有助于 障碍是自主神经系统（ANS）功能障碍。升高的生理唤醒，反映ANS 长期以来，功能障碍一直被牵涉到FXS中的学习障碍和非典型行为。 虽然ANS功能障碍与FXS和FXPM的损害有关，但研究尚未检查 ANS功能障碍的存在，发作，发展轨迹或发展后果或如何 分子遗传因素是相关的。该项目通过以下具体解决这些关键差距 目的：（1）通过预期确定基线ANS功能障碍的发作和发展轨迹 FXS（n = 30名男性）和FXPM（n = 30; 15男性和15个）在6、9、12和24个月的纵向评估 女性）与典型的对照形成对比（n = 45; 30名男性和15名女性）； （2）确定分子基因 变异与FXS和FXPM中ANS功能障碍的发作和/或发育轨迹有关； （3） 通过前瞻性纵向评估表征行为和ANS对感觉刺激的反应性 FXS和FXPM的6、9、12和24个月； （4）记录ANS功能障碍的后果 在感觉处理障碍，自适应技能，ASD症状和社交交流方面的婴儿期 同时在FXS和FXPM中同时使用24个月。这项工作将大大扩展会产生巨大的影响 有关机械基础，生物学途径和症状进展时机的信息， 对于识别治疗的靶标和时机至关重要，以减轻FXS和FXPM的症状严重程度。我们的重点 婴儿期至关重要，因为有证据表明，生命早期提供的干预措施有可能 以多维方式加速发展并改善发展轨迹。