Neuroanatomy and Cognition in Velocardiofacial Syndrome

描述（由申请人提供）：由染色体22 ql 1.2上的微缺失引起的速度心面综合征（VCFS）与导致学习障碍或智力迟钝的神经认知缺陷以及包括ADHD和焦虑的儿童期行为表型相关。据报道，多达30%的VCFS成人发展为精神分裂症（SZ），导致一些研究人员将VCFS视为SZ的遗传介导亚型。为了给VCFS儿童提供早期有效的干预措施，了解22 ql 1.2缺失对脑形态和神经认知功能的影响至关重要。最初的定量神经影像学和神经心理学研究表明，VCFS儿童表现出额叶和顶叶皮层和小脑的体积减少，注意力，执行功能，工作记忆，视觉感知和语音处理的认知障碍。这些神经解剖学的减少和认知缺陷指向两个重叠网络的破坏：大脑皮层的异模态关联区域（HASC）和皮质-小脑-丘脑-皮质回路（CCTCC）的网络。然而，HASC和CCTCC网络中的几个特定区域尚未在VCFS中进行研究。此外，由于样本量小和对照组匹配不佳，初步研究的结果是不确定的。因此，拟议的研究将使用高分辨率解剖磁共振成像和一个良好的标准化神经心理测试电池比较的形态和相关功能的HASC和CCTCC网络的40名儿童VCFS和40个年龄，性别和智商匹配的控制。对比比较将包括在运动和边缘网络，我们假设是幸免于VCFS的区域的形态和功能。潜在地，研究结果不仅将详细说明和阐明VCFS的神经解剖学和认知表型，从而促进早期和有效的干预，而且还可以作为一个病因同质模型，用于了解精神分裂症患者的形态学变化。

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.