Mamat Makliya, Chen Yiyong, Shen Wenwen, Li Lin
School of Basic Medical Sciences, Health Science Center, Ningbo University, No. 818 Fenghua Road, Jiangbei District, Ningbo, 315211, Zhejiang, People's Republic of China.
Affiliated Kangning Hospital of Ningbo University, Ningbo, 315201, Zhejiang, People's Republic of China.
Mol Autism. 2025 Jan 6;16(1):1. doi: 10.1186/s13229-024-00632-2.
Autism spectrum disorder (ASD) is characterized by difficulties in social interaction, communication challenges, and repetitive behaviors. Despite extensive research, the molecular mechanisms underlying these neurodevelopmental abnormalities remain elusive. We integrated microscale brain gene expression data with macroscale MRI data from 1829 participants, including individuals with ASD and typically developing controls, from the autism brain imaging data exchange I and II. Using fractal dimension as an index for quantifying cortical complexity, we identified significant regional alterations in ASD, within the left temporoparietal, left peripheral visual, right central visual, left somatomotor (including the insula), and left ventral attention networks. Partial least squares regression analysis revealed gene sets associated with these cortical complexity changes, enriched for biological functions related to synaptic transmission, synaptic plasticity, mitochondrial dysfunction, and chromatin organization. Cell-specific analyses, protein-protein interaction network analysis and gene temporal expression profiling further elucidated the dynamic molecular landscape associated with these alterations. These findings indicate that ASD-related alterations in cortical complexity are closely linked to specific genetic pathways. The combined analysis of neuroimaging and transcriptomic data enhances our understanding of how genetic factors contribute to brain structural changes in ASD.
自闭症谱系障碍（ASD）的特征在于社交互动困难、沟通障碍和重复行为。尽管进行了广泛研究，但这些神经发育异常背后的分子机制仍然难以捉摸。我们将来自1829名参与者（包括来自自闭症大脑成像数据交换I和II的自闭症患者和正常发育对照）的微观大脑基因表达数据与宏观MRI数据进行了整合。使用分形维数作为量化皮质复杂性的指标，我们在左颞顶叶、左周边视觉、右中央视觉、左躯体运动（包括脑岛）和左腹侧注意网络中发现了ASD患者显著的区域改变。偏最小二乘回归分析揭示了与这些皮质复杂性变化相关的基因集，这些基因集在与突触传递、突触可塑性、线粒体功能障碍和染色质组织相关的生物学功能方面得到了富集。细胞特异性分析、蛋白质-蛋白质相互作用网络分析和基因时间表达谱进一步阐明了与这些改变相关的动态分子格局。这些发现表明，ASD相关的皮质复杂性改变与特定的遗传途径密切相关。神经影像学和转录组数据的联合分析增强了我们对遗传因素如何导致ASD患者大脑结构变化的理解。
