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. ? ?
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