Neuroanatomy and Cognition in Velocardiofacial Syndrome

描述（由申请人提供）：心面快速综合征（VCFS）由染色体22ql 1.2上的微缺失引起，与神经认知缺陷相关，导致学习障碍或智力迟钝，以及儿童时期的行为表型，包括ADHD和焦虑。据报道，高达30%的成年VCFS患者会发展为精神分裂症（SZ），这使得一些研究人员将VCFS视为SZ的一种遗传介导亚型。为了给患有VCFS的儿童提供早期有效的干预措施，了解22ql 1.2缺失对大脑形态和神经认知功能的影响至关重要。初步定量神经影像学和神经心理学研究表明，患有VCFS的儿童表现出额叶、顶叶皮层和小脑的体积减少，并且在注意力、执行功能、工作记忆、视觉感知和语音处理方面存在认知障碍。这些神经解剖学上的减少和认知缺陷指向两个重叠网络的破坏：大脑皮层异模联合区域网络（HASC）和皮层-小脑-丘脑-皮层回路网络（CCTCC）。然而，在VCFS中尚未对HASC和CCTCC网络中的几个特定区域进行调查。此外，由于样本量小和对照不匹配，初步研究的结果不确定。因此，本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学测试来比较40名VCFS儿童和40名年龄、性别和智商匹配的对照组的HASC和CCTCC网络的形态和相关功能。对比比较将包括在运动和边缘网络区域的形态和功能，我们假设在VCFS中幸免。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，而且还将作为一种病因同质模型，用于理解精神分裂症患者子集的形态学变化。

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.