Telehealth Assessment of Syndromic Autism Risk in Infants

项目总结/摘要 尽管每68名美国儿童中就有1名受到影响，但自闭症谱系障碍的机制和早期病程 (ASD)在很大程度上是未知的，延迟了已知的干预措施的开始，以改变行为和神经过程， 发展目前对ASD出现的研究主要集中在ASD儿童的婴儿兄弟姐妹（ASIBs） 他们比没有家族史的孩子表现出高20倍的ASD风险。作为对这一方法的补充， 研究ASD在高危神经遗传综合征中的出现提供了以下信息：（1）ASD的普遍性， 对非ASIB的口头ASD“红旗”，考虑到大多数ASD儿童没有积极的兄弟姐妹史， 和（2）遗传和生物学途径，使ASD特征，促进机械敏感的治疗， 的部分。然而，由于高昂的费用，旅行需求， 以及评估低发病率群体的后勤挑战。此外，现有的远程保健方法， 规避这些挑战是不兼容的实验，实验室为基础的方法（如视觉atten， 任务，心理生理学）对ASD风险敏感。这种指导以患者为导向的研究职业发展- 门特奖（K23）将准备博士Tonnsen，一个临床训练的心理学家与ASD的出现专业知识 在综合征婴儿中，通过建立一个新的基于远程医疗的评估框架来解决这些障碍 进行前驱ASD监测该项目利用候选人目前在生物行为学方面的专业知识， 通过在（1）其当前专业知识之外的新ASD风险领域进行额外的指导培训， (e.g.社会沟通，运动技能），（2）基于远程医疗的临床研究，（3）机制和途径 综合征型ASD，（4）心理测量学和测量，（5）项目管理，学术写作， 伦理主要导师是发展精神病理学测量方面的专家（Don Lynam，Ph.D.）， 综合征ASD和远程医疗（伦纳德Abbeduto，博士），和社会交往发展的影响 （阿曼达塞德尔博士）。额外的培训由国家专家团队提供， (e.g.临床概况、治疗试验、保健工程）和基础（例如遗传学、小鼠模型）领域。 在她的导师团队的支持下，Tonnsen博士将开发和验证远程医疗评估电池 的前驱ASD的风险，在当地的综合征性智力残疾的婴儿（目的1）。然后她会远程申请 一组全国纵向样本的婴儿与Angelman综合征（50% ASD风险）和脆性X染色体 综合征（25-60% ASD风险;目标2），以生成后续R 01的初步数据和假设。的 拟议的研究是创新的，因为它代表了一个实质性的偏离目前的方法 框架和参与者样本的前瞻性ASD研究，奠定了基础，更高的权力， 成本更低，影响更广泛的ASD研究。此外，受保护的时间、训练和数据 该项目所提供的将使Tonnsen博士作为跨学科专家的独立之路更加清晰， 婴儿ASD综合征的微量监测

PROJECT SUMMARY / ABSTRACT Despite affecting 1 in 68 United States children, the mechanisms and early course of autism spectrum disorder (ASD) are largely unknown, delaying initiation of interventions known to alter the course of behavioral and neural development. Current studies of ASD emergence largely focus on infant siblings of children with ASD (ASIBs) who exhibit 20 times higher ASD risk than children without a family history. As a complement to this approach, studying the emergence of ASD in high-risk neurogenetic syndromes informs: (1) the generalizability of behav- ioral ASD “red flags” to non-ASIBs, given the majority of children with ASD do not have positive sibling histories, and (2) genetic and biological pathways subserving ASD features, facilitating mechanistically-sensitive treat- ments. However, syndromic ASD studies are rarely attempted in infants due to the high costs, travel demands, and logistical challenges of assessing low-incidence groups. Furthermore, existing telehealth methods that could circumvent these challenges are not compatible with experimental, laboratory-based methods (e.g. visual atten- tion tasks, psychophysiology) sensitive to ASD risk. This Mentored Patient-Oriented Research Career Develop- ment Award (K23) will prepare Dr. Tonnsen, a clinically trained psychologist with expertise in ASD emergence in syndromic infants, to address these barriers by establishing a novel, telehealth-based assessment framework for prodromal ASD surveillance. This project leverages the candidate’s current expertise in biobehavioral pre- dictors of ASD through additional mentored training in (1) new ASD risk domains outside of her current expertise (e.g. social communication, motor skills), (2) telehealth-based clinical research, (3) mechanisms and pathways of syndromic ASD, (4) psychometrics and measurement, and (5) program management, academic writing, and ethics. Primary mentors are experts in the measurement of developmental psychopathology (Don Lynam, Ph.D.), syndromic ASD and telehealth (Leonard Abbeduto, Ph.D.), and social communication development in infants (Amanda Seidl, Ph.D.). Additional training is provided by a national team of experts across both patient-oriented (e.g. clinical profiles, treatment trials, healthcare engineering) and basic (e.g. genetics, mouse models) domains. With the support of her mentorship team, Dr. Tonnsen will develop and validate a telehealth assessment battery of prodromal ASD risk in local infants with syndromic intellectual disability (Aim 1). She will then remotely apply the battery to a national longitudinal sample of infants with Angelman syndrome (50% ASD risk) and fragile X syndrome (25-60% ASD risk; Aim 2) to generate preliminary data and hypotheses for a subsequent R01. The proposed research is innovative because it represents a substantial departure from current methodological frameworks and participant samples for prospective ASD studies, laying the foundation for higher-powered, lower-cost, and wider-reaching studies of ASD emergence. Furthermore, the protected time, training, and data afforded by this project will crystallize Dr. Tonnsen’s path to independence as an interdisciplinary expert in re- mote surveillance of syndromic ASD in infants.