美国康奈尔大学医学院Conor Liston小组的研究在分子和网络水平揭示了自闭症谱系障碍（ASD）个体差异的机制。相关论文于2023年3月9日发表在《自然—神经科学》杂志上。

使用大型神经影像数据集，研究人员确定了功能性大脑网络连接的三个潜在维度，这些维度预测了ASD行为的个体差异，并且在交叉验证中是稳定的。沿着这三个维度的聚类揭示了四个可重复的ASD亚组，这些亚组在ASD相关网络中具有明显的功能连接改变，并且在独立样本中具有可重复的临床症状特征。

通过将神经影像学数据与两个独立转录组图谱的典型基因表达数据相结合，研究发现在每个亚组中，ASD相关的功能连接可以通过不同ASD相关基因集的表达区域差异来解释。这些基因集与免疫和突触功能、G蛋白偶联受体信号传导、蛋白质合成和其他过程的不同分子信号通路差异相关。总的来说，该研究结果描绘了不同ASD的非典型连接模式，这些模式涉及不同的分子信号机制。

附：英文原文

Title: Molecular and network-level mechanisms explaining individual differences in autism spectrum disorder

Author: Buch, Amanda M., Vrtes, Petra E., Seidlitz, Jakob, Kim, So Hyun, Grosenick, Logan, Liston, Conor

Issue&Volume: 2023-03-09

Abstract: The mechanisms underlying phenotypic heterogeneity in autism spectrum disorder (ASD) are not well understood. Using a large neuroimaging dataset, we identified three latent dimensions of functional brain network connectivity that predicted individual differences in ASD behaviors and were stable in cross-validation. Clustering along these three dimensions revealed four reproducible ASD subgroups with distinct functional connectivity alterations in ASD-related networks and clinical symptom profiles that were reproducible in an independent sample. By integrating neuroimaging data with normative gene expression data from two independent transcriptomic atlases, we found that within each subgroup, ASD-related functional connectivity was explained by regional differences in the expression of distinct ASD-related gene sets. These gene sets were differentially associated with distinct molecular signaling pathways involving immune and synapse function, G-protein-coupled receptor signaling, protein synthesis and other processes. Collectively, our findings delineate atypical connectivity patterns underlying different forms of ASD that implicate distinct molecular signaling mechanisms.

DOI: 10.1038/s41593-023-01259-x

Source: https://www.nature.com/articles/s41593-023-01259-x