Evans Maya M, Kim Jaekyoon, Abel Ted, Nickl-Jockschat Thomas, Stevens Hanna E
Department of Psychiatry, University of Iowa Carver College of Medicine, Iowa City, Iowa; Iowa Neuroscience Institute, University of Iowa, Iowa City, Iowa.
Department of Neuroscience and Pharmacology, University of Iowa Carver College of Medicine, Iowa City, Iowa; Iowa Neuroscience Institute, University of Iowa, Iowa City, Iowa.
Biol Psychiatry. 2024 Jan 15;95(2):102-111. doi: 10.1016/j.biopsych.2023.08.015. Epub 2023 Aug 29.
Autism spectrum disorder (ASD) is an increasingly prevalent neurodevelopmental condition characterized by social and communication deficits as well as patterns of restricted, repetitive behavior. Abnormal brain development has long been postulated to underlie ASD, but longitudinal studies aimed at understanding the developmental course of the disorder have been limited. More recently, abnormal development of the striatum in ASD has become an area of interest in research, partially due to overlap of striatal functions and deficit areas in ASD, as well as the critical role of the striatum in early development, when ASD is first detected. Focusing on the dorsal striatum and the associated symptom domain of restricted, repetitive behavior, we review the current literature on dorsal striatal abnormalities in ASD, including studies on functional connectivity, morphometry, and cellular and molecular substrates. We highlight that observed striatal abnormalities in ASD are often dynamic across development, displaying disrupted developmental trajectories. Important findings include an abnormal trajectory of increasing corticostriatal functional connectivity with age and increased striatal growth during childhood in ASD. We end by discussing striatal findings from animal models of ASD. In sum, the studies reviewed here demonstrate a key role for developmental disruptions of the dorsal striatum in the pathogenesis of ASD. Directing attention toward these findings will improve our understanding of ASD and of how associated deficits may be better addressed.
自闭症谱系障碍(ASD)是一种日益普遍的神经发育疾病,其特征为社交和沟通缺陷以及受限、重复的行为模式。长期以来,人们一直推测大脑发育异常是ASD的基础,但旨在了解该疾病发展过程的纵向研究一直很有限。最近,ASD中纹状体的异常发育已成为研究热点,部分原因是纹状体功能与ASD中的缺陷区域存在重叠,以及纹状体在首次检测到ASD的早期发育中起关键作用。本文聚焦于背侧纹状体以及受限、重复行为的相关症状领域,回顾了当前关于ASD中背侧纹状体异常的文献,包括功能连接性、形态学以及细胞和分子底物方面的研究。我们强调,在ASD中观察到的纹状体异常在整个发育过程中通常是动态的,表现出发育轨迹的紊乱。重要发现包括ASD中随着年龄增长皮质-纹状体功能连接性增加的异常轨迹以及儿童期纹状体生长增加。最后,我们讨论了ASD动物模型中的纹状体研究结果。总之,本文回顾的研究表明背侧纹状体发育紊乱在ASD发病机制中起关键作用。关注这些发现将增进我们对ASD以及如何更好地解决相关缺陷的理解。