24个月大儿童自闭症诊断及家族易感性的脑功能连接相关性

Brain functional connectivity correlates of autism diagnosis and familial liability in 24-month-olds.

作者信息

Pruett John R, Todorov Alexandre A, Hawks Zoë W, Talovic Muhamed, Nishino Tomoyuki, Petersen Steven E, Davis Savannah, Stahl Lyn, Botteron Kelly N, Constantino John N, Dager Stephen R, Elison Jed T, Estes Annette M, Evans Alan C, Gerig Guido, Girault Jessica B, Hazlett Heather, MacIntyre Leigh, Marrus Natasha, McKinstry Robert C, Pandey Juhi, Schultz Robert T, Shannon William D, Shen Mark D, Snyder Abraham Z, Styner Martin, Wolff Jason J, Zwaigenbaum Lonnie, Piven Joseph

机构信息

Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, 63110, USA.

Brooklyn Health, 195 Montague St 14, Brooklyn, NY, 11201, USA.

出版信息

J Neurodev Disord. 2025 Jul 18;17(1):40. doi: 10.1186/s11689-025-09621-9.

DOI:10.1186/s11689-025-09621-9

PMID:40682020

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12275292/

Abstract

BACKGROUND

fcMRI correlates of autism spectrum disorder (ASD) diagnosis and familial liability were studied in 24-month-olds at high (older affected sibling) and low familial likelihood for ASD.

METHODS

fcMRI comparisons of high-familial-likelihood (HL) ASD-positive (HLP, N = 23) and ASD-negative (HLN, N = 91), and low-likelihood ASD-negative (LLN, N = 27) 24-month-olds from the Infant Brain Imaging Study (IBIS) Network were conducted, employing object oriented data analysis (OODA), support vector machine (SVM) classification, and network-level fcMRI enrichment analyses.

RESULTS

OODA (alpha = 0.0167, 3 comparisons) revealed differences in HLP and LLN fcMRI matrices (p = 0.012), but none for HLP versus HLN (p = 0.047) nor HLN versus LLN (p = 0.225). SVM distinguished HLP from HLN (accuracy = 99%, PPV = 96%, NPV = 100%), based on connectivity involving many networks. SVM accurately classified (non-training) LLN subjects with 100% accuracy. Enrichment analyses identified a cross-group fcMRI difference in the posterior cingulate default mode network 1 (pcDMN1)- temporal default mode network (tDMN) pair (p = 0.0070). Functional connectivity for implicated connections in these networks was consistently lower in HLP and HLN than in LLN (p = 0.0461 and 0.0004). HLP did not differ from HLN (p = 0.2254). Secondary testing showed HL children with low ASD behaviors still differed from LLN (p = 0.0036).

CONCLUSIONS

24-month-old high-familial-likelihood infants show reduced intra-DMN connectivity, a potential neural finding related to familial liability, while widely distributed functional connections correlate with ASD diagnosis.

摘要

背景

在24个月大、患自闭症谱系障碍（ASD）可能性高（有年长患病同胞）和可能性低的婴幼儿中，研究了ASD诊断及家族易感性的功能连接性磁共振成像（fcMRI）相关性。

方法

对来自婴儿脑成像研究（IBIS）网络的24个月大、家族患病可能性高（HL）的ASD阳性（HLP，N = 23）和ASD阴性（HLN，N = 91），以及家族患病可能性低的ASD阴性（LLN，N = 27）婴幼儿进行fcMRI比较，采用面向对象数据分析（OODA）、支持向量机（SVM）分类和网络水平的fcMRI富集分析。

结果

OODA（α = 0.0167，3次比较）显示HLP和LLN的fcMRI矩阵存在差异（p = 0.012）但HLP与HLN之间无差异（p = 0.047），HLN与LLN之间也无差异（p = 0.225）。基于涉及多个网络的连通性，SVM能将HLP与HLN区分开（准确率 = 99%，阳性预测值 = 96%，阴性预测值 = 100%）。SVM对（非训练）LLN受试者的准确分类率为100%。富集分析确定了后扣带回默认模式网络1（pcDMN1）-颞叶默认模式网络（tDMN）对中的跨组fcMRI差异（p = 0.0070）。这些网络中相关连接的功能连通性在HLP和HLN中始终低于LLN（p = 0.0461和0.0004）。HLP与HLN无差异（p = 0.2254）。二次测试显示ASD行为较少的HL儿童与LLN仍有差异（p = 0.0036）。