Luo Tingting, Zhang Manxue, Li Sixun, Situ Mingjing, Liu Pei, Wang Meiwen, Tao Yujie, Zhao Shengnan, Wang Zhuo, Yang Yanping, Huang Yi
Mental Health Center, West China Hospital of Sichuan University, Chengdu, China.
Front Psychiatry. 2024 May 16;15:1384134. doi: 10.3389/fpsyt.2024.1384134. eCollection 2024.
Autism Spectrum Disorder (ASD) is a common neurodevelopmental disorder emerging in early childhood, with heterogeneous clinical outcomes across individuals. This study aims to recognize neuroimaging genetic factors associated with outcomes of ASD after a 4-year follow-up.
A total of 104 ASD children were included in this study; they underwent clinical assessments, MRI data acquisition, and the whole exome sequencing (WES). Exome functional risk score (EFRS) was calculated based on WES; and two modalities of brain connectivity were constructed based on MRI data, that is functional connectivity (FC) for functional MRI (fMRI), and individual differential structural covariance network (IDSCN) for structural MRI (sMRI), to explore the neuroimaging genetic biomarker of outcomes of ASD children.
Regression analysis found EFRS predicts social adaptability at the 4-year follow-up (Y = -0.013X + 9.29, = 0.003). We identified 19 pairs of FC associated with autism symptoms severity at follow-up, 10 pairs of FC and 4 pairs of IDSCN associated with social adaptability at follow-up, and 10 pairs of FC associated with ASD EFRS by support vector regression (SVR). Related brain regions with prognostic predictive effects are mainly distributed in superior frontal gyrus, occipital cortex, temporal cortex, parietal cortex, paracentral lobule, pallidum, and amygdala for FC, and temporal cortex, thalamus, and hippocampus for IDSCN. Mediation model showed that ASD EFRS affects the social communication of ASD children through the mediation of FC between left middle occipital gyrus and left pallidum (RMSEA=0.126, CMIN=80.66, DF=42, < 0.001, CFI=0.867, AIC=152).
Our findings underscore that both EFRS and brain connectivity can predict social adaptability, and that brain connectivity serving as mediator in the relationship of EFRS and behaviors of ASD, suggesting the intervention targets in the future clinical application.
自闭症谱系障碍（ASD）是一种常见的神经发育障碍，在幼儿期出现，个体间临床结果存在异质性。本研究旨在识别4年随访后与ASD结果相关的神经影像遗传因素。
本研究共纳入104名ASD儿童；他们接受了临床评估、MRI数据采集和全外显子测序（WES）。基于WES计算外显子功能风险评分（EFRS）；并基于MRI数据构建两种脑连接模式，即功能MRI（fMRI）的功能连接（FC）和结构MRI（sMRI）的个体差异结构协方差网络（IDSCN），以探索ASD儿童结果的神经影像遗传生物标志物。
回归分析发现EFRS可预测4年随访时的社会适应性（Y = -0.013X + 9.29， = 0.003）。通过支持向量回归（SVR），我们识别出19对与随访时自闭症症状严重程度相关的FC、10对与随访时社会适应性相关的FC和4对IDSCN，以及10对与ASD EFRS相关的FC。具有预后预测作用的相关脑区，对于FC主要分布在额上回、枕叶皮质、颞叶皮质、顶叶皮质、中央旁小叶、苍白球和杏仁核，对于IDSCN主要分布在颞叶皮质、丘脑和海马体。中介模型显示，ASD EFRS通过左侧枕中回和左侧苍白球之间的FC中介作用影响ASD儿童的社会沟通（RMSEA = 0.126，CMIN = 80.66，DF = 42，< 0.001，CFI = 0.867，AIC = 152）。
我们的研究结果强调，EFRS和脑连接都可以预测社会适应性，并且脑连接在EFRS与ASD行为的关系中起中介作用，这为未来临床应用提供了干预靶点。
