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. ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
1R01MH065481-01A2
Application #
6680879
Study Section
Biobehavioral and Behavioral Processes 3 (BBBP)
Program Officer
Rumsey, Judith M
Project Start
2003-06-01
Project End
2006-05-31
Budget Start
2003-06-01
Budget End
2004-05-31
Support Year
1
Fiscal Year
2003
Total Cost
$268,920
Indirect Cost
Name
Upstate Medical University
Department
Psychiatry
Type
Schools of Medicine
DUNS #
058889106
City
Syracuse
State
NY
Country
United States
Zip Code
13210
Vorstman, Jacob A S; Breetvelt, Elemi J; Duijff, Sasja N et al. (2015) Cognitive decline preceding the onset of psychosis in patients with 22q11.2 deletion syndrome. JAMA Psychiatry 72:377-85
Radoeva, Petya D; Coman, Ioana L; Salazar, Cynthia A et al. (2014) Association between autism spectrum disorder in individuals with velocardiofacial (22q11.2 deletion) syndrome and PRODH and COMT genotypes. Psychiatr Genet 24:269-72
Antshel, Kevin M; Hendricks, Kaitlin; Shprintzen, Robert et al. (2013) The longitudinal course of attention deficit/hyperactivity disorder in velo-cardio-facial syndrome. J Pediatr 163:187-93.e1
Kunwar, Arun; Ramanathan, Seethalakshmi; Nelson, Joshua et al. (2012) Cortical gyrification in velo-cardio-facial (22q11.2 deletion) syndrome: a longitudinal study. Schizophr Res 137:20-5
Radoeva, Petya D; Coman, Ioana L; Antshel, Kevin M et al. (2012) Atlas-based white matter analysis in individuals with velo-cardio-facial syndrome (22q11.2 deletion syndrome) and unaffected siblings. Behav Brain Funct 8:38
Friedman, Marcia A; Miletta, Nathanial; Roe, Cheryl et al. (2011) Cleft palate, retrognathia and congenital heart disease in velo-cardio-facial syndrome: a phenotype correlation study. Int J Pediatr Otorhinolaryngol 75:1167-72
Kates, Wendy R; Antshel, Kevin M; Faraone, Stephen V et al. (2011) Neuroanatomic predictors to prodromal psychosis in velocardiofacial syndrome (22q11.2 deletion syndrome): a longitudinal study. Biol Psychiatry 69:945-52
Kates, Wendy R; Bansal, Ravi; Fremont, Wanda et al. (2011) Mapping cortical morphology in youth with velocardiofacial (22q11.2 deletion) syndrome. J Am Acad Child Adolesc Psychiatry 50:272-282.e2
Antshel, Kevin M; Shprintzen, Robert; Fremont, Wanda et al. (2010) Cognitive and psychiatric predictors to psychosis in velocardiofacial syndrome: a 3-year follow-up study. J Am Acad Child Adolesc Psychiatry 49:333-44
Roizen, Nancy J; Higgins, Anne M; Antshel, Kevin M et al. (2010) 22q11.2 deletion syndrome: are motor deficits more than expected for IQ level? J Pediatr 157:658-61

Showing the most recent 10 out of 26 publications