Abstract：
The neuroanatomy of autism spectrum disorder (ASD) shows highly heterogeneous developmental trajectories across individuals. Mapping atypical brain development onto clinical phenotypes, and establishing their molecular underpinnings, is therefore crucial for patient stratification and subtyping. In this longitudinal study we examined intra- and inter-individual differences in the developmental trajectory of cortical thickness (CT) in childhood and adolescence, and their genomic underpinnings, in 33 individuals with ASD and 37 typically developing controls (aged 11-18 years). Moreover, we aimed to link regional atypical CT development to intra-individual variations in restricted and repetitive behavior (RRB) over a two-year time period. Individuals with ASD showed significantly reduced cortical thinning in several of the brain regions functionally related to wider autism symptoms and traits (e.g., fronto-temporal and cingulate cortices). The spatial patterns of the neuroanatomical differences in CT were enriched for genes known to be associated with ASD at a genetic and transcriptomic level. Further, intra-individual differences in CT correlated with within-subject variability in the severity of RRBs. Our findings represent an important step towards characterizing the neuroanatomical underpinnings of ASD across development based upon measures of CT. Moreover, our findings provide important novel insights into the link between microscopic and macroscopic pathology in ASD, as well as their relationship with different clinical ASD phenotypes.
摘要：
自闭症谱系障碍（ASD）的神经解剖学显示出个体之间高度异质的发育轨迹。将非典型脑发育映射到临床表型，建立它们的分子基础，因此对于患者分层和分型至关重要。在这项纵向研究中，我们检查了儿童期和青春期皮质厚度（CT）发育轨迹的个体内和个体间差异，以及它们的基因组基础，33例ASD患者和37例通常发展为对照（年龄11-18岁）。此外，我们的目标是将区域非典型CT发展与限制和重复行为(RRB)在两年时间内的个体差异联系起来.患有ASD的个体在功能上与更广泛的自闭症症状和特征相关的几个大脑区域显示出显着减少的皮质变薄（例如，前颞骨和扣带回皮质）。在遗传和转录组水平上，已知与ASD相关的基因丰富了CT神经解剖学差异的空间模式。Further,CT的个体差异与受试者体内RRB严重程度的变异性相关.我们的发现代表了根据CT测量来表征ASD在整个发展过程中的神经解剖学基础的重要一步。此外，我们的发现为ASD的微观和宏观病理学之间的联系提供了重要的新见解，以及它们与不同临床ASD表型的关系。
