Department of Forensic and Neurodevelopmental Sciences, and the Sackler Institute for Translational Neurodevelopmental Sciences, Institute of Psychiatry, Psychology and Neuroscience, King's College, London, UK.
Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, University Hospital, Goethe University, Frankfurt, Germany.
Cereb Cortex. 2020 Sep 3;30(10):5281-5292. doi: 10.1093/cercor/bhaa108.
22q11.2 deletion syndrome (22q11.2DS) is a genetic condition accompanied by a range of psychiatric manifestations, including autism spectrum disorder (ASD). It remains unknown, however, whether these symptoms are mediated by the same or distinct neural mechanisms as in idiopathic ASD. Here, we examined differences in lGI associated with ASD in 50 individuals with 22q11.2DS (n = 25 with ASD, n = 25 without ASD) and 81 individuals without 22q11.2DS (n = 40 with ASD, n = 41 typically developing controls). We initially utilized a factorial design to identify the set of brain regions where lGI is associated with the main effect of 22q11.2DS, ASD, and with the 22q11.2DS-by-ASD interaction term. Subsequently, we employed canonical correlation analysis (CCA) to compare the multivariate association between variability in lGI and the complex clinical phenotype of ASD between 22q11.2DS carriers and noncarriers. Across approaches, we established that even though there is a high degree of clinical similarity across groups, the associated patterns of lGI significantly differed between carriers and noncarriers of the 22q11.2 microdeletion. Our results suggest that ASD symptomatology recruits different neuroanatomical underpinnings across disorders and that 22q11.2DS individuals with ASD represent a neuroanatomically distinct subgroup that differs from 22q11.2DS individuals without ASD and from individuals with idiopathic ASD.
22q11.2 缺失综合征(22q11.2DS)是一种伴有多种精神表现的遗传病症,包括自闭症谱系障碍(ASD)。然而,目前尚不清楚这些症状是否与特发性 ASD 具有相同或不同的神经机制。在这里,我们研究了 50 名 22q11.2DS 患者(25 名 ASD 患者,25 名非 ASD 患者)和 81 名无 22q11.2DS 患者(40 名 ASD 患者,41 名典型发育对照者)的 ASD 相关局部脑区灰质体积(lGI)差异。我们首先采用因子设计来识别与 22q11.2DS、ASD 的主要效应以及 22q11.2DS 与 ASD 的交互作用相关的脑区 lGI 集合。随后,我们采用典型相关分析(CCA)比较 22q11.2DS 携带者和非携带者的 lGI 变异性与 ASD 复杂临床表型之间的多变量关联。通过两种方法,我们发现,尽管各组间具有高度的临床相似性,但携带者和非携带者的 lGI 相关模式存在显著差异。我们的研究结果表明,ASD 症状在不同障碍之间具有不同的神经解剖学基础,并且携带 22q11.2 微缺失的 ASD 患者代表了一个具有神经解剖学特征的亚组,与无 22q11.2DS 的 ASD 患者和特发性 ASD 患者不同。