title: Reduced brain activation during inhibitory control in children withCOMTVal/Val genotype.
abstract: Behavioral undercontrol is a well-established risk factor for substance use disorder, identifiable at an early age well before the onset of substance use. However, the biological mechanistic structure underlying the behavioral undercontrol/substance use relationship is not well understood. The enzyme catecholO-methyltransferase (COMT) catabolizes dopamine and norepinephrine in the prefrontal cortex and striatum, brain regions involved in behavioral control. The goal of this work was to investigate the association between genetic variation in COMT functioning and fronto-striatal brain functioning during successful inhibitory control, a critical aspect of behavioral control.
  
  
  
  Participants were 65 (22 female) 7-12 year olds who were genotyped for the functionalCOMTVal158Met (rs4680) single-nucleotide polymorphism and underwent functional magnetic resonance imaging while performing a go/no-go task. The majority of the sample (80%) had at least one parent with a history of alcohol use disorder and were thus at heightened risk for substance use disorders.
  
  
  
  There was a significant main effect of genotype on brain activation in left and right putamen during successful versus failed inhibition and in right inferior frontal gyrus/insula during successful inhibition versus baseline. Follow-up tests revealed that Met homozygotes had greater activation in each region relative to Val homozygotes.
  
  
  
  These results are relevant for understanding how specific genes influence brain functioning related to underlying risk factors for substance use disorders and other disinhibitory psychopathologies.
authors.affiliation: Department of Psychiatry University of Michigan Ann Arbor MI USA; Addiction Center University of Michigan Ann Arbor MI USA.
authors.forename: Lora M
authors.initials: LM
authors.lastname: Cope
authors.affiliation: Department of Psychiatry University of Michigan Ann Arbor MI USA; Addiction Center University of Michigan Ann Arbor MI USA.
authors.forename: Jillian E
authors.initials: JE
authors.lastname: Hardee
authors.affiliation: Department of Psychiatry University of Michigan Ann Arbor MI USA; Addiction Center University of Michigan Ann Arbor MI USA.
authors.forename: Mary E
authors.initials: ME
authors.lastname: Soules
authors.affiliation: Department of Psychiatry University of Michigan Ann Arbor MI USA; Molecular & Behavioral Neuroscience Institute University of Michigan Ann Arbor MI USA; Department of Human Genetics University of Michigan Ann Arbor MI USA.
authors.forename: Margit
authors.initials: M
authors.lastname: Burmeister
authors.affiliation: Department of Psychiatry University of Michigan Ann Arbor MI USA; Addiction Center University of Michigan Ann Arbor MI USA.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Zucker
authors.affiliation: Department of Psychiatry University of Michigan Ann Arbor MI USA; Addiction Center University of Michigan Ann Arbor MI USA.
authors.forename: Mary M
authors.initials: MM
authors.lastname: Heitzeg
mesh_terms: D001921:Brain / Q000000981:diagnostic imaging / Q000201:enzymology / Q000502:physiology*; D002394:Catechol O-Methyltransferase / Q000235:genetics*; D002648:Child; D005260:Female; D006801:Humans; D007266:Inhibition, Psychological; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D020641:Polymorphism, Single Nucleotide; D013647:Task Performance and Analysis; D014633:Valine / Q000235:genetics
chemical_list: C588010:COMT protein, human; D002394:Catechol O-Methyltransferase; D014633:Valine
keywords: catechol O‐methyltransferase; children; dopamine; functional magnetic resonance imaging; go/no‐go; inferior frontal gyrus; insula; putamen; response inhibition; substance use disorder risk