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)网络拨款的竞争性延续。最初的拨款支持对患有自闭症高家族风险(HR)的婴儿在6个月、12个月和24个月时进行前瞻性、纵向的大脑和行为检查。到这项初步研究完成时，将有400名HR和150名低风险婴儿进入这项研究。结果显示，24个月大的HR婴儿在6个月大时出现视觉定向和运动行为障碍，这可能为这些婴儿在12个月大时出现自闭症的明确特征(社交缺陷、重复行为)奠定基础。在24个月大的自闭症婴儿中，6个月大时可以检测到白质束发育异常，在6-24个月期间观察到白质束发育的进一步广泛异常和脑体积增长率的增加。因此，我们的研究首次证实，这种大脑变化与ASD行为异常的出现是同时发生的。综上所述，这些发现指出，第一年(早在6个月大的时候)的大脑和行为变化在自闭症行为的发生和发展中至关重要。在这项应用中，我们建议通过更早(3个月)、更频繁(3、6、9、12、15、24个月)和更深入地检查200名HR和60名LR婴儿的大脑和行为发展轨迹来跟踪这些发现，以更全面地了解在这一关键重要时期之前以及与自闭症定义特征的出现相吻合的大脑-行为关系。我们还建议对原始样本400名36至60个月大的HR受试者进行后续行为/诊断评估，这一时期自闭症的诊断被认为更稳定。这将使我们能够绘制大脑和行为发育的轨迹图，并测试临床ASD诊断和发育轨迹变异之间的关联。最后，我们建议对儿童和家庭层面的特征进行分析，以阐明600名人力资源受试者联合队列中未来自闭症的早期预测模型。在早期发育阶段描绘大脑和行为轨迹，以及在婴儿期、临床诊断前和出生后大脑可塑性较强的时期根据临床前风险标记预测自闭症诊断的能力，当儿童可能从早期检测和干预中获得最大好处时，有可能显著改善受影响个人的生活。

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.