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However, the biological mechanistic structure underlying the behavioral undercontrol\/substance use relationship is not well understood. The enzyme catechol<jats:italic>O<\/jats:italic>\u2010methyltransferase (<jats:styled-content style=\"fixed-case\">COMT<\/jats:styled-content>) 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<jats:styled-content style=\"fixed-case\">COMT<\/jats:styled-content>functioning and fronto\u2010striatal brain functioning during successful inhibitory control, a critical aspect of behavioral control.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Participants were 65 (22 female) 7\u201312\u00a0year olds who were genotyped for the functional<jats:italic><jats:styled-content style=\"fixed-case\">COMT<\/jats:styled-content><\/jats:italic>Val<jats:sup>158<\/jats:sup>Met (rs4680) single\u2010nucleotide polymorphism and underwent functional magnetic resonance imaging while performing a go\/no\u2010go 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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>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\u2010up tests revealed that Met homozygotes had greater activation in each region relative to Val homozygotes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>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.<\/jats:p><\/jats:sec>","DOI":"10.1002\/brb3.577","type":"journal-article","created":{"date-parts":[[2016,10,12]],"date-time":"2016-10-12T21:27:38Z","timestamp":1476307658000},"source":"Crossref","is-referenced-by-count":6,"title":["Reduced brain activation during inhibitory control in children with<i><scp>COMT<\/scp><\/i>Val\/Val genotype"],"prefix":"10.1002","volume":"6","author":[{"given":"Lora M.","family":"Cope","sequence":"first","affiliation":[{"name":"Department of Psychiatry University of Michigan Ann Arbor MI USA"},{"name":"Addiction Center University of Michigan Ann Arbor MI USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jillian E.","family":"Hardee","sequence":"additional","affiliation":[{"name":"Department of Psychiatry University of Michigan Ann Arbor MI USA"},{"name":"Addiction Center University of Michigan Ann Arbor MI USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mary E.","family":"Soules","sequence":"additional","affiliation":[{"name":"Department of Psychiatry University of Michigan Ann Arbor MI USA"},{"name":"Addiction Center University of Michigan Ann Arbor MI USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Margit","family":"Burmeister","sequence":"additional","affiliation":[{"name":"Department of Psychiatry University of Michigan Ann Arbor MI USA"},{"name":"Molecular &amp; Behavioral Neuroscience Institute University of Michigan Ann Arbor MI USA"},{"name":"Department of Human Genetics University of Michigan Ann Arbor MI USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert A.","family":"Zucker","sequence":"additional","affiliation":[{"name":"Department of Psychiatry University of Michigan Ann Arbor MI USA"},{"name":"Addiction Center University of Michigan Ann Arbor MI USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mary M.","family":"Heitzeg","sequence":"additional","affiliation":[{"name":"Department of Psychiatry University of Michigan Ann Arbor MI USA"},{"name":"Addiction Center University of Michigan Ann Arbor MI USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2016,10,5]]},"reference":[{"volume-title":"Manual for the ASEBA school\u2010age forms & profiles","year":"2001","author":"Achenbach T. 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