Predictors of Cognitive Development in Autism Spectrum Disorder

描述（由申请人提供）：现有的关于儿童中期的研究表明，一些ASD儿童在这一时期的智商和其他方面的认知功能有了显著的提高，而另一些儿童则保持稳定或进一步落后。随着强化早期干预的增加，目前尚不清楚这些早期研究的结果是否适用于ASD儿童。鉴于儿童早期和中期发展的认知能力为以后的能力提供了重要的基础，并且是青少年和成人结果的最强预测因素，因此对儿童中期认知发展的不清楚构成了我们对ASD理解的重大差距。为了缩小这一差距，我们建议对自闭症个体进行纵向研究，重点关注来自加州大学戴维斯分校心智研究所自闭症表型组项目（APP）的一组特征良好的儿童的中期儿童。189名ASD幼儿和90名典型发育（TYP）幼儿在儿童早期（2-3.5岁或T1）进行了评估。这些儿童中的一部分在5-6.5岁（T2）时接受额外的行为评估，并为应用程序提供试点数据。在本研究中，我们将重新评估279名进入童年中期（8-10岁或T3）的原始队列。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的预测因素。根据我们的试点数据和文献，我们假设他们会表现出3种智力发展轨迹。这包括：1)稳定的低发展轨迹；2)稳定的高发展轨迹；3)变革者的发展轨迹。我们假设，在T3时，稳定高组的成员资格将通过T1时更好的执行注意力控制和更少的自闭症相关社会影响症状来预测；在T3时，与稳定低水平组相比，改变者组的成员资格将通过在T1时没有倒退和更少的自闭症相关交流症状来预测。在目标#2中，我们测试了两种机制模型，即强化早期干预如何促进ASD患者的积极童年中期功能。其中包括“海马体补偿模型”，该模型提出，在一些儿童中，干预促进了海马体的神经可塑性，从而导致儿童中期记忆力、智商和学术功能的改善，以及“社会注意力模型”，这表明，在T3阶段学业、社交和适应功能较好的儿童，早期干预的强度与执行注意力控制和社会沟通发展之间存在正相关。该申请解决了IACC战略计划问题2和4；NIMH RDoC建议研究执行力控制。

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.