title: Neural correlates of inhibitory control and functional genetic variation in the dopamine D4 receptor gene.
abstract: BACKGROUND
  The dopamine D4 receptor gene (DRD4) has been implicated in psychiatric disorders in which deficits of self-regulation are a prominent feature (e.g., attention-deficit hyperactivity disorder and substance use disorders) and in dopamine D4 receptor insensitivity within prefrontal regions of the brain. Our hypothesis was that carriers of 7-repeats in the Variable Number of Tandem Repeats (VNTR) of DRD4 (7R+) would recruit prefrontal brain regions involved in successful inhibitory control to a lesser degree than non-carriers (7R-) and demonstrate less inhibitory control as confirmed by observation of locally reduced blood oxygenation level dependent (BOLD) % signal change and lower accuracy while performing "No-Go" trials of a Go/No-Go task.
  
  
  METHODS
  Participants (age=18, n=62, 33 females) were recruited from the general population of the St. Louis, Missouri region. Participants provided a blood or saliva sample for genotyping, completed drug and alcohol-related questionnaires and IQ testing, and performed a Go/No-Go task inside of a 3T fMRI scanner.
  
  
  RESULTS
  Go/No-Go task performance did not significantly differ between 7R+ and 7R- groups. Contrast of brain activity during correct "No-Go" trials with a non-target letter baseline revealed significant BOLD activation in a network of brain regions previously implicated in inhibitory control including bilateral dorsolateral prefrontal, inferior frontal, middle frontal, medial prefrontal, subcortical, parietal/temporal, and occipital/cerebellar brain regions. Mean BOLD % signal change during "No-Go" trials was significantly modulated by DRD4 genotype, with 7R+ showing a lower hemodynamic response than 7R- in right anterior prefrontal cortex/inferior frontal gyrus, left premotor cortex, and right occipital/cerebellar areas. Follow-up analyses suggested that 7-repeat status accounted for approximately 5-6% of the variance in the BOLD response during "No-Go" trials.
  
  
  CONCLUSIONS
  The DRD4 7-repeat allele may alter dopaminergic function in brain regions involved in inhibitory control. When individuals must inhibit a prepotent motor response, presence of this allele may account for 5-6% of the variance in BOLD signal in brain regions critically associated with inhibitory control, but its influence may be associated with a greater effect on brain than on behavior in 18-year-olds from the general population.
authors.affiliation: Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA. Electronic address: mulligar@psychiatry.wustl.edu.
authors.forename: Richard C
authors.initials: RC
authors.lastname: Mulligan
authors.affiliation: Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA; Pason Systems Corporation, Calgary, Alberta, Canada.
authors.forename: Sean D
authors.initials: SD
authors.lastname: Kristjansson
authors.affiliation: Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA.
authors.forename: Angela M
authors.initials: AM
authors.lastname: Reiersen
authors.affiliation: Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA.
authors.forename: Andres S
authors.initials: AS
authors.lastname: Parra
authors.affiliation: Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA.
authors.forename: Andrey P
authors.initials: AP
authors.lastname: Anokhin
mesh_terms: D000293:Adolescent; D001921:Brain / Q000098:blood supply / Q000502:physiology*; D001931:Brain Mapping; D002755:Choice Behavior / Q000502:physiology; D056344:Executive Function / Q000502:physiology*; D005260:Female; D056726:Genetic Association Studies; D005838:Genotype; D006801:Humans; D021621:Imaging, Three-Dimensional; D007266:Inhibition, Psychological; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging; D008297:Male; D018598:Minisatellite Repeats / Q000235:genetics*; D010100:Oxygen / Q000097:blood; D050638:Receptors, Dopamine D4 / Q000235:genetics*; D012927:Social Control, Informal; D055815:Young Adult
chemical_list: D050638:Receptors, Dopamine D4; D010100:Oxygen
keywords: DRD4; Dopamine; Executive function; Inhibitory control; Response inhibition; fMRI
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