Predictors of Cognitive Development in Autism Spectrum Disorder

描述(由申请人提供)：现有的关于童年中期的研究表明，一些患有自闭症的儿童在这段时间内在智商和其他认知功能方面表现出显著的改善，而其他儿童则稳定或进一步落后。随着强化早期干预措施的增加，目前尚不清楚这些较老的研究结果是否适用于ASD儿童。鉴于儿童早期和中期发展的认知能力为后来的能力提供了关键的基础，并且是青少年和成人结果的最强预测因子，因此对儿童中期认知发展的缺乏清楚地构成了我们对自闭症的理解的一个重大差距。为了缩小这一差距，我们建议对自闭症患者进行一项纵向研究，重点是加州大学戴维斯分校心智研究所自闭症表现组项目(APP)中一组具有良好特征的儿童的童年中期。在儿童早期(2-3.5岁或T1)对189名患有自闭症的幼儿和90名典型发育(TYP)儿童进行了评估。这些儿童中的一部分在5-6.5岁(T2)时接受了额外的行为评估，并为该应用程序提供了试点数据。在拟议的研究中，我们将在279名儿童达到童年中期(8-10岁或T3)时重新评估最初的队列。在目标1中，我们将a)检查认知功能；b)确定儿童早期和中期智力功能/智商的不同发展轨迹，以及这些轨迹中成员的预测因素。我们假设，根据我们的试点数据和文献，他们将显示出3条智力发展的轨迹。它们包括：1)稳定的低发展轨迹；2)稳定的高发展轨迹；3)变化者的发展轨迹。我们假设，在t3时，通过更好的执行注意力控制和较少的自闭症相关社会影响症状，将预测在t3时加入稳定高水平组的成员；而在t3时，与稳定低组相比，在t3时，通过没有回归和较少的自闭症相关沟通症状来预测变更组的成员资格。在目标2中，我们测试了两个机械性模型，即早期强化干预如何促进自闭症患者积极的童年中期功能。其中包括“海马体补偿模型”和“社会注意模型”，该模型提出，在一些儿童中，干预促进了海马区的神经可塑性，从而导致儿童中期记忆、智商和学习功能的改善，以及“社会注意模型”，该模型表明，在T3具有更好的学习、社会和适应功能的儿童中，早期干预的强度与执行注意控制和社会交流发展之间将存在正相关。这个应用程序解决了IACC战略计划问题2和4；以及NIMH RDoC关于研究执行注意控制的建议。

DESCRIPTION (provided by applicant): Existing studies of middle childhood suggest that some children with ASD show significant improvements in IQ and other aspects of cognitive functioning during this period, while others stabilize or fall further behind. With the increased availability of intensive early intervention, it is not clear that findings from these older studie are applicable to children with ASD now. Given that cognitive abilities developed through early and middle childhood provide a critical foundation for later competencies, and are the strongest predictors of adolescent and adult outcomes, the lack of clarity about cognitive development during middle childhood constitutes a significant gap in our understanding of ASD. To close this gap we propose to conduct a longitudinal study of individuals with ASD that focuses on middle childhood in a well-characterized cohort of children from the UC Davis MIND Institute Autism Phenome Project (APP). One hundred and eighty nine toddlers with ASD and 90 with typical development (TYP) were assessed during early childhood (at 2-3.5 years or T1). A subset of these children received additional behavioral assessments when they were 5-6.5 years old (T2) and provide pilot data for the application. In the proposed study, we will reassess the original cohort of 279 when they reach middle childhood (at 8-10 years or T3). In Aim #1 we will a) examine cognitive functioning; and b) identify distinct developmental trajectories of intellectual functioning/IQ between early and middle childhood and predictors of membership in these trajectories. We hypothesize that they will show 3 trajectories of intellectual development based on our pilot data and the literature. These include the: 1) the Stable Low developmental trajectory; 2) the Stable High developmental trajectory; and 3) the Changers developmental trajectory. We hypothesize that membership in the Stable High group at T3, will be predicted by better executive attentional control and fewer autism-related social affect symptoms at T1; and that membership in the Changers group at T3, vs. the Stable Low group, will be predicted by the absence of regression and fewer autism-related communication symptoms at T1. In Aim #2, we test 2 mechanistic models of how intensive early intervention might promote positive middle childhood functioning in individuals with ASD. These include the "Hippocampal Compensation Model," which proposes that in some children intervention promotes neuroplasticity of the hippocampus which then leads to improvements in memory, IQ, and academic functioning in middle childhood and the "Social Attention Model," which suggests that in children with better academic, social, and adaptive functioning at T3 there will be a positive association between intensity of early intervention, and executive attentional control and social communication development. This application addresses IACC Strategic Plan Questions 2 and 4; and the NIMH RDoC recommendation to study executive attentional control.