title: Effect of dopamine transporter gene (SLC6A3) variation on dorsal anterior cingulate function in attention-deficit/hyperactivity disorder.
abstract: Although attention-deficit/hyperactivity disorder (ADHD) is associated both with brain alterations in attention and executive function (EF) circuitry and with genetic variations within the dopamine system (including the dopamine transporter gene [SLC6A3]), few studies have directly investigated how genetic variations are linked to brain alterations. We sought to examine how a polymorphism in the 3' untranslated region (UTR) of SLC6A3, associated with ADHD in meta-analysis, might contribute to variation in dorsal anterior cingulate cortex (dACC) function in subjects with ADHD. We collected fMRI scans of 42 individuals with ADHD, all of European descent and over the age of 17, while they performed the multi-source interference task (MSIT), a cognitive task shown to activate dACC. SLC6A3 3' UTR variable number tandem repeat (VNTR) polymorphisms were genotyped and brain activity was compared for groups based on allele status. ADHD individuals homozygous for the 10R allele showed significant hypoactivation in the left dACC compared to 9R-carriers. Exploratory analysis also showed trends toward hypoactivation in the 10R homozygotes in left cerebellar vermis and right lateral prefrontal cortex. Further breakdown of genotype groups showed similar activation in individuals heterozygous and homozygous for the 9R allele. Alterations in activation of attention and EF networks found previously to be involved in ADHD are likely influenced by SLC6A3 genotype. This genotype may contribute to heterogeneity of brain alterations found within ADHD samples.
authors.affiliation: Department of Psychiatry, Clinical and Research Programs in Pediatric Psychopharmacology and Adult ADHD, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.|Division of Graduate Medical Sciences, Ph.D. Program in Behavioral Neuroscience, Boston University School of Medicine, Boston, Massachusetts.
authors.forename: Ariel B
authors.initials: AB
authors.lastname: Brown
authors.affiliation: Department of Psychiatry, Clinical and Research Programs in Pediatric Psychopharmacology and Adult ADHD, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.
authors.forename: Joseph
authors.initials: J
authors.lastname: Biederman
authors.affiliation: Department of Psychiatry, Clinical and Research Programs in Pediatric Psychopharmacology and Adult ADHD, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.|Department of Psychiatry, Psychiatric Neuroimaging Research Program, Massachusetts General Hospital and Harvard Medical School, Boston Massachusetts.
authors.forename: Eve M
authors.initials: EM
authors.lastname: Valera
authors.affiliation: Department of Psychiatry, Clinical and Research Programs in Pediatric Psychopharmacology and Adult ADHD, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.
authors.forename: Alysa E
authors.initials: AE
authors.lastname: Doyle
authors.affiliation: Department of Psychiatry, Psychiatric Neuroimaging Research Program, Massachusetts General Hospital and Harvard Medical School, Boston Massachusetts.
authors.forename: George
authors.initials: G
authors.lastname: Bush
authors.affiliation: Department of Psychiatry, Clinical and Research Programs in Pediatric Psychopharmacology and Adult ADHD, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.
authors.forename: Thomas
authors.initials: T
authors.lastname: Spencer
authors.affiliation: Department of Psychiatry, Clinical and Research Programs in Pediatric Psychopharmacology and Adult ADHD, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.
authors.forename: Michael C
authors.initials: MC
authors.lastname: Monuteaux
authors.affiliation: Department of Psychiatry, Clinical and Research Programs in Pediatric Psychopharmacology and Adult ADHD, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.
authors.forename: Eric
authors.initials: E
authors.lastname: Mick
authors.affiliation: Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, Massachusetts.
authors.forename: Susan
authors.initials: S
authors.lastname: Whitfield-Gabrieli
authors.affiliation: Departments of Neurology and Radiology Services, Harvard Medical School, Boston, Massachusetts.|Center for Morphometric Analysis, Massachusetts General Hospital, Boston, Massachusetts.
authors.forename: Nikos
authors.initials: N
authors.lastname: Makris
authors.affiliation: Department of Psychiatry, Clinical and Research Programs in Pediatric Psychopharmacology and Adult ADHD, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.
authors.forename: Peter S
authors.initials: PS
authors.lastname: LaViolette
authors.affiliation: Division of Graduate Medical Sciences, Ph.D. Program in Behavioral Neuroscience, Boston University School of Medicine, Boston, Massachusetts.|Departments of Psychiatry, Neurology, and Anatomy & Neurobiology, Boston University School of Medicine, Boston, Massachusetts.|US Department of Veterans Affairs Healthcare System, Boston, Massachusetts.
authors.forename: Marlene
authors.initials: M
authors.lastname: Oscar-Berman
authors.affiliation: Department of Psychiatry and Behavioral Sciences, SUNY Upstate Medical University, Syracuse, New York.
authors.forename: Stephen V
authors.initials: SV
authors.lastname: Faraone
authors.affiliation: Department of Psychiatry, Clinical and Research Programs in Pediatric Psychopharmacology and Adult ADHD, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.|The Massachusetts Mental Health Center Public Psychiatry Division of the Beth Israel Deaconess Medical Center, Department of Psychiatry, Harvard Medical School Department of Psychiatry, Boston, Massachusetts.
authors.forename: Larry J
authors.initials: LJ
authors.lastname: Seidman
mesh_terms: D000293:Adolescent; D000328:Adult; D001289:Attention Deficit Disorder with Hyperactivity / Q000235:genetics*; D003071:Cognition; D050483:Dopamine Plasma Membrane Transport Proteins / Q000235:genetics*; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D006179:Gyrus Cinguli / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008875:Middle Aged; D008959:Models, Neurological; D012306:Risk
chemical_list: D050483:Dopamine Plasma Membrane Transport Proteins; C493214:SLC6A3 protein, human
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