Abnormal cortical activation during response inhibition in 22q11.2 deletion syndrome.
22q11.2 deletion syndrome (22q11.2DS) is a well-known genetic risk factor for schizophrenia. The catechol-O-methyltransferase (COMT) gene falls within the 22q11.2 minimal critical region of the deletion. Brain activity, as measured by functional magnetic resonance imaging (fMRI) during a Go/NoGo, response inhibition task was assessed in adolescents with 22q11.2DS (n = 13), typically developing (TD) controls (n = 14), and controls with developmental disability (DD, n = 9). Subjects with 22q11.2DS were also genotyped for the COMT Met/Val polymorphism. Groups did not differ on task performance. However, compared to both control groups, the 22q11.2DS group showed greater brain activation within left parietal regions. Comparison of brain activation between 22q11.2DS Met and Val subgroups revealed significantly increased activation (Met>Val) in the cingulate but not the dorsolateral prefrontal cortex. These preliminary findings suggest that adolescents with 22q11.2DS compensate for executive dysfunction via recruitment of parietal regions. Further, the COMT Met subgroup of 22q11.2DS may recruit additional cingulate activation for tasks requiring attention and inhibition. 22q11.2DS is a unique model for learning about the deleterious effects of decreased dosage of the COMT gene on brain function.
Gothelf
Doron
D
The Behavioral Neurogenetics Center, Child Psychiatry Department, Schneider Children's Medical Center of Israel, Petah Tiqwa, Israel. gothelf@post.tau.ac.il
Hoeft
Fumiko
F
Hinard
Christine
C
Hallmayer
Joachim F
JF
Stoecker
John Van Dover
JV
Antonarakis
Stylianos E
SE
Morris
Michael A
MA
Reiss
Allan L
AL
D000293:Adolescent; D000328:Adult; D001931:Brain Mapping; D016022:Case-Control Studies; D002394:Catechol O-Methyltransferase / Q000235:genetics; D002540:Cerebral Cortex / Q000002:abnormalities* / Q000098:blood supply / Q000473:pathology / Q000503:physiopathology; D002872:Chromosome Deletion; D002892:Chromosomes, Human, Pair 22; D002658:Developmental Disabilities / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted / Q000379:methods; D007266:Inhibition, Psychological; D008279:Magnetic Resonance Imaging; D008297:Male; D008715:Methionine / Q000235:genetics; D009483:Neuropsychological Tests; D010100:Oxygen / Q000097:blood; D012559:Schizophrenia / Q000235:genetics*; D014633:Valine / Q000235:genetics
D008715:Methionine; D002394:Catechol O-Methyltransferase; D014633:Valine; D010100:Oxygen