Abstract
Chromosome 22q11.2 Deletion Syndrome (22q11.2DS) is caused by the most common human microdeletion, and it is associated with cognitive impairments across many domains. While impairments in cognitive control have been described in children with 22q11.2DS, the nature and development of these impairments are not clear. Children with 22q11.2DS and typically developing children (TD) were tested on four well-validated tasks aimed at measuring specific foundational components of cognitive control: response inhibition, cognitive flexibility, and working memory. Molecular assays were also conducted in order to examine genotype of catechol-O-methyltransferase (COMT), a gene located within the deleted region in 22q11.2DS and hypothesized to play a role in cognitive control. Mixed model regression analyses were used to examine group differences, as well as age-related effects on cognitive control component processes in a cross-sectional analysis. Regression models with COMT genotype were also conducted in order to examine potential effects of the different variants of the gene. Response inhibition, cognitive flexibility, and working memory were impaired in children with 22q11.2DS relative to TD children, even after accounting for global intellectual functioning (as measured by full-scale IQ). When compared with TD individuals, children with 22q11.2DS demonstrated atypical age-related patterns of response inhibition and cognitive flexibility. Both groups demonstrated typical age-related associations with working memory. The results of this cross-sectional analysis suggest a specific aberration in the development of systems mediating response inhibition in a sub-set of children with 22q11.2DS. It will be important to follow up with longitudinal analyses to directly examine these developmental trajectories, and correlate neurocognitive variables with clinical and adaptive outcome measures.
Highlights
Chromosome 22q11.2 Deletion Syndrome (22q11.2DS) results from a 1.5- to 3-megabase microdeletion on the long (q) arm of chromosome 22 (Carlson et al, 1997) and occurs in approximately one in 2000–4000 live births (Oskarsdóttir et al, 2004; Shprintzen, 2008)
Response inhibition was measured by accuracy on No-Go trials that were parametrically manipulated for difficulty
There was a significant effect of No-Go condition on accuracy in typically developing children (TD) children, such that when No-Go trials were preceded by increasing numbers of Go trials, TD children had greater accuracy [F(2, 96) = 11.51, p < 0.0001; mean accuracy = 70.5[18.7]%, 77.7[14.7]%, and 81.7[14.0]% for one, three, and five preceding Go trials, respectively]
Summary
Chromosome 22q11.2 Deletion Syndrome (22q11.2DS) results from a 1.5- to 3-megabase microdeletion on the long (q) arm of chromosome 22 (Carlson et al, 1997) and occurs in approximately one in 2000–4000 live births (Oskarsdóttir et al, 2004; Shprintzen, 2008) Children with this disorder have mild to moderate intellectual impairments (median full scale IQ 70 ± 15) (Scambler, 2000) and a cognitive profile with difficulties on a range of functions including attention and quantitative processing (Simon et al, 2005; Simon, 2008; Simon and Luck, 2011), as well as cognitive control (Bish et al, 2005; Sobin et al, 2005). Based on this line of evidence, a better understanding of cognitive control component processes in children with 22q11.2DS, a group with a genetically conferred risk for schizophrenia, might help to identify specific cognitive functions that could act both as biomarkers for conversion risk, and as specific targets for intervention that might reduce that risk
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