Effect of dopamine transporter gene (SLC6A3) variation on dorsal anterior cingulate function in attention-deficit/hyperactivity disorder.
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.
Brown
Ariel B
AB
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.
Biederman
Joseph
J
Department of Psychiatry, Clinical and Research Programs in Pediatric Psychopharmacology and Adult ADHD, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.
Valera
Eve M
EM
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.
Doyle
Alysa E
AE
Department of Psychiatry, Clinical and Research Programs in Pediatric Psychopharmacology and Adult ADHD, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.
Bush
George
G
Department of Psychiatry, Psychiatric Neuroimaging Research Program, Massachusetts General Hospital and Harvard Medical School, Boston Massachusetts.
Spencer
Thomas
T
Department of Psychiatry, Clinical and Research Programs in Pediatric Psychopharmacology and Adult ADHD, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.
Monuteaux
Michael C
MC
Department of Psychiatry, Clinical and Research Programs in Pediatric Psychopharmacology and Adult ADHD, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.
Mick
Eric
E
Department of Psychiatry, Clinical and Research Programs in Pediatric Psychopharmacology and Adult ADHD, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.
Whitfield-Gabrieli
Susan
S
Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, Massachusetts.
Makris
Nikos
N
Departments of Neurology and Radiology Services, Harvard Medical School, Boston, Massachusetts.|Center for Morphometric Analysis, Massachusetts General Hospital, Boston, Massachusetts.
LaViolette
Peter S
PS
Department of Psychiatry, Clinical and Research Programs in Pediatric Psychopharmacology and Adult ADHD, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.
Oscar-Berman
Marlene
M
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.
Faraone
Stephen V
SV
Department of Psychiatry and Behavioral Sciences, SUNY Upstate Medical University, Syracuse, New York.
Seidman
Larry J
LJ
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.
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
D050483:Dopamine Plasma Membrane Transport Proteins; C493214:SLC6A3 protein, human
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