Choi Eun Jung, Vandewouw Marlee M, Taylor Margot J, Arnold Paul D, Brian Jessica, Crosbie Jennifer, Kelley Elizabeth, Lai Meng-Chuan, Liu Xudong, Schachar Russell J, Lerch Jason P, Anagnostou Evdokia
Autism Research Centre, Bloorview Research Institute, Holland Bloorview Kids Rehabilitation Hospital, Toronto, ON, Canada; Neurosciences & Mental Health, Research Institute, The Hospital for Sick Children, Toronto, Canada.
Autism Research Centre, Bloorview Research Institute, Holland Bloorview Kids Rehabilitation Hospital, Toronto, ON, Canada; Neurosciences & Mental Health, Research Institute, The Hospital for Sick Children, Toronto, Canada; Diagnostic Imaging, The Hospital for Sick Children, Toronto, ON, Canada; Institute of Biomedical Engineering, University of Toronto, ON, Canada.
Neuroimage Clin. 2020;28:102476. doi: 10.1016/j.nicl.2020.102476. Epub 2020 Oct 27.
Children with neurodevelopmental disorders (NDDs) share common behavioural manifestations despite distinct categorical diagnostic criteria. Here, we examined canonical resting-state network connectivity in three diagnostic groups (autism spectrum disorder, attention-deficit/hyperactivity disorder and paediatric obsessive-compulsive disorder) and typically developing controls (TD) in a large single-site sample (N = 407), applying diagnosis-based and dimensional approaches to understand underlying neurobiology across NDDs. Each participant's functional network graphs were computed using five graph metrics. In diagnosis-based comparisons, an analysis of covariance was performed to compare all NDDs to TD, followed by pairwise comparisons between NDDs. In the dimensional approach, participants' functional network graphs were correlated with continuous behavioural measures, and a data-driven k-means clustering analysis was applied to determine if subgroups of participants were seen, without diagnostic information having been included. In the diagnosis-based comparisons, children with NDDs did not differ significantly from the TD group and the NDD categorical groups also did not differ significantly from each other, across all graph metrics. In the dimensional, diagnostic-independent approach, however, subcortical functional connectivity was significantly correlated with participants' general adaptive functioning across all participants. The clustering analysis identified an optimal solution of two clusters, and participants assigned in the same data-driven cluster were highly heterogeneous in diagnosis. Neither cluster exclusively contained a specific diagnostic group, nor did NDDs separate cleanly from TDs. Each participant's distance ratio between the two clusters was significantly correlated with general adaptive functioning, social deficits and attentional problems. Our results suggest the neurobiological similarity and dissimilarity between NDDs need to be investigated beyond DSM/ICD-based, behaviourally-defined diagnostic categories.
尽管神经发育障碍（NDDs）有不同的分类诊断标准，但患有这些疾病的儿童有共同的行为表现。在此，我们在一个大型单中心样本（N = 407）中，研究了三个诊断组（自闭症谱系障碍、注意力缺陷多动障碍和小儿强迫症）以及典型发育对照组（TD）的典型静息态网络连通性，应用基于诊断和维度的方法来理解整个NDDs的潜在神经生物学。使用五个图指标计算每个参与者的功能网络图。在基于诊断的比较中，进行协方差分析以比较所有NDDs与TD，随后对NDDs之间进行两两比较。在维度方法中，将参与者的功能网络图与连续行为测量值相关联，并应用数据驱动的k均值聚类分析来确定是否能看到参与者亚组，且不包括诊断信息。在基于诊断的比较中，在所有图指标上，患有NDDs的儿童与TD组没有显著差异，NDD分类组之间也没有显著差异。然而，在维度的、与诊断无关的方法中，皮质下功能连通性与所有参与者的一般适应性功能显著相关。聚类分析确定了两个聚类的最优解，并且在同一数据驱动聚类中分配的参与者在诊断上高度异质。没有一个聚类专门包含特定的诊断组，NDDs也没有与TDs清晰分开。每个参与者在两个聚类之间的距离比与一般适应性功能、社交缺陷和注意力问题显著相关。我们的结果表明，需要超越基于《精神疾病诊断与统计手册》（DSM）/《国际疾病分类》（ICD）、基于行为定义的诊断类别来研究NDDs之间的神经生物学异同。
