Computer Engineering Program, University of Wisconsin-Stout, Wisconsin.
Department of Psychiatry, University of Illinois, Chicago, Illinois.
Hum Brain Mapp. 2018 Jan;39(1):232-248. doi: 10.1002/hbm.23838. Epub 2017 Oct 8.
Occurring in at least 1 in 3,000 live births, chromosome 22q11.2 deletion syndrome (22q11DS) produces a complex phenotype that includes a constellation of medical complications such as congenital cardiac defects, immune deficiency, velopharyngeal dysfunction, and characteristic facial dysmorphic features. There is also an increased incidence of psychiatric diagnosis, especially intellectual disability and ADHD in childhood, lifelong anxiety, and a strikingly high rate of schizophrenia spectrum disorders, which occur in around 30% of adults with 22q11DS. Using innovative computational connectomics, we studied how 22q11DS affects high-level network signatures of hierarchical modularity and its intrinsic geometry in 55 children with confirmed 22q11DS and 27 Typically Developing (TD) children. Results identified 3 subgroups within our 22q11DS sample using a K-means clustering approach based on several midline structural measures-of-interests. Each subgroup exhibited distinct patterns of connectome abnormalities. Subtype 1, containing individuals with generally healthy-looking brains, exhibited no significant differences in either modularity or intrinsic geometry when compared with TD. By contrast, the more anomalous 22q11DS Subtypes 2 and 3 brains revealed significant modular differences in the right hemisphere, while Subtype 3 (the most anomalous anatomy) further exhibited significantly abnormal connectome intrinsic geometry in the form of left-right temporal disintegration. Taken together, our findings supported an overall picture of (a) anterior-posteriorly differential interlobar frontotemporal/frontoparietal dysconnectivity in Subtypes 2 and 3 and (b) differential intralobar dysconnectivity in Subtype 3. Our ongoing studies are focusing on whether these subtypes and their connnectome signatures might be valid biomarkers for predicting the degree of psychosis-proneness risk found in 22q11DS. Hum Brain Mapp 39:232-248, 2018. © 2017 Wiley Periodicals, Inc.
发生在至少 1/3000 活产儿中的 22q11.2 号染色体缺失综合征（22q11DS）产生了一种复杂的表型，包括一系列的医疗并发症，如先天性心脏缺陷、免疫缺陷、软腭功能障碍和特征性的面部畸形特征。精神科诊断的发病率也有所增加，特别是儿童时期的智力障碍和 ADHD，终身焦虑，以及精神分裂症谱系障碍的发病率极高，约 30%的 22q11DS 成年人患有该疾病。我们使用创新的计算连接组学方法，研究了 22q11DS 如何影响 55 名确诊的 22q11DS 儿童和 27 名典型发育（TD）儿童的高层次网络特征的分层模块性及其内在几何结构。结果使用基于几个中线结构指标的 K-均值聚类方法，在我们的 22q11DS 样本中识别出 3 个亚组。每个亚组都表现出不同的连接组异常模式。亚组 1 包含大脑外观通常健康的个体，与 TD 相比，在模块性或内在几何结构方面没有显著差异。相比之下，更异常的 22q11DS 亚组 2 和 3 大脑的右半球显示出显著的模块差异，而亚组 3（最异常的解剖结构）进一步表现出左右颞叶解体形式的显著异常连接组内在几何结构。总的来说，我们的研究结果支持以下观点：（a）22q11DS 亚组 2 和 3 存在前-后额颞/额顶叶连接障碍；（b）亚组 3 存在不同的叶内连接障碍。我们正在进行的研究集中于这些亚组及其连接组特征是否可以作为预测 22q11DS 中精神病倾向风险程度的有效生物标志物。《人类大脑图谱》39:232-248, 2018。© 2017 Wiley Periodicals, Inc.
