Neuroanatomy and Cognition in Velocardiofacial Syndrome

描述(由申请人提供)：由染色体22ql 1.2上的微缺失引起的血管紧张症候群(VCFS)，与导致学习障碍或智力低下的神经认知缺陷以及儿童时期包括ADHD和焦虑在内的行为表型有关。据报道，多达30%的VCFS成年人会患上精神分裂症(SZ)，这导致一些研究人员将VCFS视为SZ的一种遗传亚型。为了对VCFS儿童提供早期有效的干预，了解22ql 1.2缺失对脑形态和神经认知功能的影响是至关重要的。初步的定量神经成像和神经心理学研究表明，VCFS儿童额叶和顶叶皮质以及小脑的体积减少，注意力、执行功能、工作记忆、视觉感知和语音处理方面的认知障碍。这些神经解剖学的减少和认知缺陷表明两个重叠的网络被破坏：大脑皮层的异模联结区域网络(HASC)和皮质-小脑-丘脑-皮质回路(CCTCC)。然而，HASC和CCTCC网络中的几个具体区域尚未在VCFS中进行调查。此外，由于样本较少和对照配对较差，初步研究的结果并不确定。因此，这项拟议的研究将使用高分辨率解剖磁共振成像和标准化的神经心理测试组件来比较40名VCFS儿童和40名年龄、性别和智商匹配的对照组儿童HASC和CCTCC网络的形态和相关功能。我们将对运动和边缘网络中包含的区域的形态和功能进行对比比较，我们假设这些区域在VCFS中是不存在的。潜在地，这些发现不仅将明确和阐明VCFS的神经解剖学和认知表型，从而促进早期和有效的干预，而且还将作为一个病因同质模型来理解精神分裂症患者子集的形态变化。

DESCRIPTION (provided by applicant): Velocardiofacial syndrome (VCFS), caused by a microdeletion on chromosome 22ql 1.2, is associated with neurocognitive deficits resulting in learning disabilities or mental retardation, and a behavioral phenotype in childhood that includes ADHD and anxiety. Up to 30% of adults with VCFS are reported to develop schizophrenia (SZ), leading some researchers to view VCFS as a genetically mediated subtype of SZ. In order to provide early and effective interventions to children with VCFS, it is critical that we understand the impact of the 22ql 1.2 deletion on brain morphology and neurocognitive function. Initial quantitative neuroimaging and neuropsychological studies suggest that children with VCFS demonstrate volumetric reductions in frontal and parietal cortex and the cerebellum, and cognitive impairments in attention, executive function, working memory, visual perception and phonological processing. These neuroanatomic reductions and cognitive deficits point to the disruption of two overlapping networks: the network of heteromodal association regions of the cerebral cortex (HASC) and the cortical-cerebellar-thalamic-cortical circuit (CCTCC). However, several of the specific regions within the HASC and CCTCC networks have not yet been investigated in VCFS. Moreover, results of initial studies are inconclusive, due to small samples and poorly matched controls. Accordingly, the proposed study will use high-resolution anatomic magnetic resonance imaging and a well-standardized neuropsychological test battery to compare the morphology and associated functions of the HASC and CCTCC networks of 40 children with VCFS and 40 age-, gender-, and IQ-matched controls. Contrast comparisons will be made of the morphology and functions of regions included within the motor and limbic networks, which we hypothesize are spared in VCFS. Potentially, the findings will not only specify and elucidate the neuroanatomic and cognitive phenotype of VCFS, thereby facilitating early and effective interventions, but also serve as an etiologically homogeneous model for understanding morphological changes in a subset of individuals with schizophrenia.