Geng Shujie, Dai Yuan, Rolls Edmund T, Liu Yuqi, Zhang Yue, Deng Lin, Chen Zilin, Feng Jianfeng, Li Fei, Cao Miao
Institute of Science and Technology for Brain-Inspired Intelligence, Fudan University, Shanghai, China.
Key Laboratory of Computational Neuroscience and Brain-Inspired Intelligence (Fudan University), Ministry of Education, Shanghai, China.
Mol Psychiatry. 2025 Jan 15. doi: 10.1038/s41380-025-02890-9.
To understand the neural mechanism of autism spectrum disorder (ASD) and developmental delay/intellectual disability (DD/ID) that can be associated with ASD, it is important to investigate individuals at an early stage with brain, behavioural and also genetic measures, but such research is still lacking. Here, using the cross-sectional sMRI data of 1030 children under 8 years old, we employed developmental normative models to investigate the atypical development of gray matter volume (GMV) asymmetry in individuals with ASD without DD/ID, ASD with DD/ID and individuals with only DD/ID, and their associations with behavioral and clinical measures and transcription profiles. By extracting the individual deviations of patients from the typical controls with normative models, we found a commonly abnormal pattern of GMV asymmetry across all ASD children: more rightward laterality in the inferior parietal lobe and precentral gyrus, and higher individual variability in the temporal pole. Specifically, ASD with DD/ID children showed a severer and more extensive abnormal pattern in GMV asymmetry deviation values, which was linked with both ASD symptoms and verbal IQ. The abnormal pattern of ASD without DD/ID children showed higher and more extensive individual variability, which was linked with ASD symptoms only. DD/ID children showed no significant differences from healthy population in asymmetry. Lastly, the GMV laterality patterns of all patient groups were significantly associated with both shared and unique gene expression profiles. Our findings provide evidence for rightward GMV asymmetry of some cortical regions in young ASD children (1-7 years) in a large sample (1030 cases), show that these asymmetries are related to ASD symptoms, and identify genes that are significantly associated with these differences.
为了了解自闭症谱系障碍(ASD)以及可能与ASD相关的发育迟缓/智力残疾(DD/ID)的神经机制,在早期阶段对个体进行大脑、行为以及基因方面的测量研究很重要,但此类研究仍较为缺乏。在此,我们使用1030名8岁以下儿童的横断面结构磁共振成像(sMRI)数据,采用发育规范模型来研究无DD/ID的ASD个体、伴有DD/ID的ASD个体以及仅患有DD/ID的个体中灰质体积(GMV)不对称性的非典型发育情况,以及它们与行为和临床测量指标及转录谱的关联。通过用规范模型提取患者相对于典型对照的个体偏差,我们发现所有ASD儿童中GMV不对称性存在一种共同的异常模式:顶下小叶和中央前回的右侧化程度更高,颞极的个体变异性更大。具体而言,伴有DD/ID的ASD儿童在GMV不对称性偏差值方面表现出更严重、更广泛的异常模式,这与ASD症状和言语智商均相关。无DD/ID的ASD儿童的异常模式表现出更高且更广泛的个体变异性,仅与ASD症状相关。DD/ID儿童在不对称性方面与健康人群无显著差异。最后,所有患者组的GMV侧化模式均与共享和独特的基因表达谱显著相关。我们的研究结果为大样本(1030例)中1 - 7岁ASD幼儿某些皮质区域的GMV右侧不对称性提供了证据,表明这些不对称性与ASD症状相关,并鉴定出与这些差异显著相关的基因。