UW Autism Center of Excellence

华盛顿大学自闭症卓越中心

• 批准号: 7911673
• 负责人: Bryan H King
• 金额: $ 217.98万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-08-06 至 2012-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7911673
• 关键词: UW; Autism; Center; Excellence

The UW ACE theme centers on a comprehensive developmental model of risk, risk processes, symptom emergence, and adaptation in autism spectrum disorder (ASD). According to this model, early autism risk factors (genetic/familial, brain, and environmental) lead to risk processes, namely, altered patterns of interaction between the child and his/her environment, which contribute to the abnormal development of neural circuitry and atypical behaviors. Project I seeks to identify autism risk genes through quantitative trait locus analysis, and also seeks to expand the set of component traits (endophenotypes) for which there is evidence for a genetic basis. In a sample of infant siblings of children with autism ("infant sibs"), Project II will investigate whether neurophysiological risk indices measured at 6-7 mos of age will improve our ability to identify infants who will develop ASD by age 2 years. This project also will investigate the efficacy of an early intervention that is designed to enhance early social responsiveness and communication for reducing autism symptoms in infant sibs by age 2 years. Project III will examine the predictive validity of measures of early prelinguistic abilities as risk indices for language impairment and ASD in infant sibs, and determine whether early intervention can influence the development of speech perception, speech preferences, and acquisition of speech in such at-risk infants. Project IV will identify early manifestations of abnormal brain development in 12-month old infant sibs using magnetic resonance imaging (MRI) and magnetic resonance spectroscopic imaging (MRSI), and examine relationships between these brain measures and clinical course and symptom onset. This project also will conduct brain imaging studies on adolescents with ASD who have been previously imaged by our group at age 3-4, 6-7, and 9-10 years to identify brain developmental changes that may be related to onset of seizures and behavioral decline during adolescence. Project V will conduct a prospective longitudinal cohort study of children with ASD who are transitioning into adolescence to investigate the role of genetic, child phenotypic, and family risk and protective factors in development of associated symptoms, such as depressive and anxiety symptoms. In a younger longitudinal cohort, this project also will conduct a follow-up study of a randomized, controlled trial of early intensive behavioral intervention to examine the long term effects on both core and associated symptoms. The proposed studies bring together strong expertise by UW investigators in early intervention, infant social cognition and prelinguistic development, child clinical and developmental psychology, child psychiatry, developmental cognitive neuroscience and neurophysiology, magnetic resonance imaging and spectroscopy, and quantitative approaches to genetic research. This combined expertise has allowed us to design projects aimed at discovering both etiologic pathways and effective treatments for autism spectrum disorder.

UW ACE的主题是自闭症谱系障碍（ASD）的风险、风险过程、症状出现和适应的综合发展模型。根据该模型，早期自闭症风险因素（遗传/家族、大脑和环境）会导致风险过程，即儿童与其环境之间互动模式的改变，从而导致神经回路的异常发育和非典型行为。项目一旨在通过数量性状位点分析确定自闭症风险基因，并寻求扩大有遗传基础证据的组成性状（内表型）集。在自闭症儿童的婴儿兄弟姐妹样本（“婴儿兄弟姐妹”）中，项目II将调查在6-7岁时测量的神经生理风险指数是否会提高我们识别2岁前将发展为自闭症的婴儿的能力。该项目还将调查旨在提高早期社会反应和沟通的早期干预的效果，以减少2岁前婴儿的自闭症症状。项目III将检验早期前语言能力作为婴儿同胞语言障碍和ASD风险指标的预测有效性，并确定早期干预是否可以影响这些风险婴儿的语言感知、语言偏好和语言习得的发展。项目IV将使用磁共振成像（MRI）和磁共振光谱成像（MRSI）识别12个月大的婴儿同胞大脑发育异常的早期表现，并检查这些大脑测量与临床过程和症状发作之间的关系。该项目还将对患有ASD的青少年进行脑成像研究，这些青少年在3-4岁、6-7岁和9-10岁时进行过成像，以确定可能与青春期癫痫发作和行为下降有关的大脑发育变化。项目V将对过渡到青春期的ASD儿童进行一项前瞻性纵向队列研究，以调查遗传、儿童表型、家庭风险和保护因素在相关症状（如抑郁和焦虑症状）发展中的作用。在较年轻的纵向队列中，本项目还将对早期强化行为干预的随机对照试验进行随访研究，以检查对核心症状和相关症状的长期影响。这些拟议的研究汇集了华盛顿大学研究人员在早期干预、婴儿社会认知和语言前发展、儿童临床和发展心理学、儿童精神病学、发展认知神经科学和神经生理学、磁共振成像和光谱学以及基因研究定量方法方面的强大专业知识。这种综合的专业知识使我们能够设计旨在发现自闭症谱系障碍的病因途径和有效治疗方法的项目。