title: Effects of a functional COMT polymorphism on brain anatomy and cognitive function in adults with velo-cardio-facial syndrome.
abstract: BACKGROUND
  Velo-cardio-facial syndrome (VCFS) is associated with deletions at chromosome 22q11, abnormalities in brain anatomy and function, and schizophrenia-like psychosis. Thus it is assumed that one or more genes within the deleted region are crucial to brain development. However, relatively little is known about how genetic variation at 22q11 affects brain structure and function. One gene on 22q11 is catechol-O-methyltransferase (COMT): an enzyme that degrades dopamine and contains a functional polymorphism (Val158Met) affecting enzyme activity. Here, we investigated the effect of COMT Val158Met polymorphism on brain anatomy and cognition in adults with VCFS.
  
  
  METHODS
  The COMT Val158Met polymorphism was genotyped for 26 adults with VCFS on whom DNA was available. We explored its effects on regional brain volumes using hand tracing approaches; on regional grey- and white-matter density using computerized voxel-based analyses; and measures of attention, IQ, memory, executive and visuospatial function using a comprehensive neuropsychological test battery.
  
  
  RESULTS
  After corrections for multiple comparisons Val-hemizygous subjects, compared with Met-hemizygotes, had a significantly larger volume of frontal lobes. Also, Val-hemizygotes had significantly increased grey matter density in cerebellum, brainstem, and parahippocampal gyrus, and decreased white matter density in the cerebellum. No significant effects of COMT genotype on neurocognitive performance were found.
  
  
  CONCLUSIONS
  COMT genotype effects on brain anatomy in VCFS are not limited to frontal regions but also involve other structures previously implicated in VCFS. This suggests variation in COMT activity is implicated in brain development in VCFS.
authors.affiliation: Department of Psychiatry, Academic Medical Centre, Amsterdam, The Netherlands. t.a.vanamelsvoort@amc.uva.nl
authors.forename: T
authors.initials: T
authors.lastname: van Amelsvoort
authors.forename: J
authors.initials: J
authors.lastname: Zinkstok
authors.forename: M
authors.initials: M
authors.lastname: Figee
authors.forename: E
authors.initials: E
authors.lastname: Daly
authors.forename: R
authors.initials: R
authors.lastname: Morris
authors.forename: M J
authors.initials: MJ
authors.lastname: Owen
authors.forename: K C
authors.initials: KC
authors.lastname: Murphy
authors.forename: L
authors.initials: L
authors.lastname: De Haan
authors.forename: D H
authors.initials: DH
authors.lastname: Linszen
authors.forename: B
authors.initials: B
authors.lastname: Glaser
authors.forename: D G M
authors.initials: DG
authors.lastname: Murphy
mesh_terms: D000328:Adult; D001921:Brain / Q000201:enzymology / Q000254:growth & development / Q000473:pathology*; D002394:Catechol O-Methyltransferase / Q000235:genetics* / Q000378:metabolism; D002872:Chromosome Deletion; D002892:Chromosomes, Human, Pair 22 / Q000235:genetics*; D003072:Cognition Disorders / Q000175:diagnosis* / Q000201:enzymology / Q000235:genetics*; D004062:DiGeorge Syndrome / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D005260:Female; D005787:Gene Frequency; D006801:Humans; D006984:Hypertrophy / Q000473:pathology; D008297:Male; D008715:Methionine / Q000235:genetics; D009483:Neuropsychological Tests / Q000706:statistics & numerical data*; D011110:Polymorphism, Genetic / Q000235:genetics*; D011618:Psychotic Disorders / Q000175:diagnosis / Q000201:enzymology / Q000235:genetics; D014633:Valine / Q000235:genetics
chemical_list: D008715:Methionine; D002394:Catechol O-Methyltransferase; D014633:Valine