A Longitudinal MRI Study of Infants at Risk for Autism

描述（由申请人提供）：项目摘要本申请是自闭症卓越中心（ACE）网络补助金的竞争延续。最初的拨款支持对自闭症高家族风险（HR）婴儿在6个月、12个月和24个月时的大脑和行为进行前瞻性纵向检查。在完成本初步研究时，将有400名HR和150名低风险婴儿进入本研究。结果显示，在24个月时继续患有自闭症的HR婴儿在6个月时的视觉定向和运动行为有障碍，这可能为在12个月大时在这些婴儿中观察到的自闭症定义特征（社交缺陷，重复行为）的出现奠定了基础。在24个月时被归类为自闭症的婴儿中，在6个月时可检测到异常的白色束发育（1），在6-24个月期间观察到白色束发育的进一步广泛异常和脑体积增长率增加。因此，我们的研究第一次确定，这种大脑变化与ASD中行为异常的出现同时发生。总的来说，这些发现表明，在第一年（以及早在6个月大的时候），大脑和行为的变化在自闭症行为的发生和发展中至关重要。在这项申请中，我们建议跟进这些发现，（3个月），更频繁（3，6，9，12，15，24个月）和更深入的检查200 HR和60 LR婴儿的大脑和行为发育的轨迹，更全面地了解大脑行为关系在这一至关重要的时期之前，并与自闭症的定义特征的出现相一致。我们还建议对我们最初的400名36至60个月大的HR受试者进行随访行为/诊断评估，当时自闭症的诊断被认为是更稳定的。这将使我们能够绘制大脑和行为发展的轨迹，并测试临床ASD诊断与发展轨迹变化之间的关联。最后，我们建议进行分析的儿童和家庭水平的特点，阐明早期预测模型，后来自闭症的联合队列的600 HR科目。在早期发育中描绘大脑和行为轨迹，以及在婴儿期、临床诊断之前和出生后大脑可塑性显著增强的时期从临床前风险标志物中预测自闭症诊断的能力，儿童可能从早期检测和干预中获益最大，有可能显着改善受影响个体的生活。

DESCRIPTION (provided by applicant): Project Summary This application is a competing continuation of an Autism Center of Excellence (ACE) Network grant. The initial grant supported a prospective, longitudinal examination of brain and behavior at 6, 12 and 24 months in infants at high familial risk (HR) for autism. By the completion of this initial study 400 HR and 150 low risk infants will have entered this study. Results reveal that HR infants who go on to have autism at 24 months have impairments in visual orienting and motor behavior at 6 months of age, which may lay the foundation for the emergence of the defining features of autism (social deficits, repetitive behaviors) observed in these same infants by 12 months of age. Aberrant white matter tract development is detectable by 6 months of age in infants classified as autistic at 24 months (1), with further widespread abnormalities in white matter tract development and an increased rate of brain volume growth observed over the 6-24 month period. Thus, our research establishes, for the first time, that such brain changes occur concurrently with the emergence of behavioral abnormalities in ASD. Taken together, these findings point to brain and behavior changes during the 1st year (and as early as 6 months of age) as being critically important in the onset and development of autistic behavior. In this application we propose to follow up these findings by conducting earlier (3 months), more frequent (3, 6, 9, 12, 15, 24 months) and more in depth examination of the trajectories of brain and behavior development in 200 HR and 60 LR infants, to more fully understand brain-behavior relationships during this critically important period preceding and coinciding with the emergence of the defining features of autism. We also propose to conduct follow up behavioral/diagnostic evaluations of our original sample of 400 HR subjects at 36 to 60 months of age, a time when the diagnosis of autism is considered to be more stable. This will allow us to map the trajectories of brain and behavior development and test the association between clinical ASD diagnosis and variation in developmental trajectories. Finally we propose to conduct an analysis of child and family level characteristics relevant to elucidating an early prediction model of later autism in the joint cohort of 600 HR subjects. The delineation of brain and behavior trajectories in early development and the ability to predict autism diagnosis from preclinical risk markers during infancy, prior to clinical diagnosis and during a period of substantial post-natal brain plasticity, when children may benefit maximally from early detection and intervention, has the potential to significantly improve the lives of affected individuals.