title: Nitric oxide synthase genotype modulation of impulsivity and ventral striatal activity in adult ADHD patients and healthy comparison subjects.
abstract: OBJECTIVE
  Attention deficit hyperactivity disorder (ADHD) is a highly heritable disorder. The NOS1 gene encoding nitric oxide synthase is a candidate gene for ADHD and has been previously linked with impulsivity. In the present study, the authors investigated the effect of a functional variable number of tandem repeats (VNTR) polymorphism in NOS1 (NOS1 exon 1f-VNTR) on the processing of rewards, one of the cognitive deficits in ADHD.
  
  
  METHODS
  A sample of 136 participants, consisting of 87 adult ADHD patients and 49 healthy comparison subjects, completed a reward-related impulsivity task. A total of 104 participants also underwent functional magnetic resonance imaging during a reward anticipation task. The effect of the NOS1 exon 1f-VNTR genotype on reward-related impulsivity and reward-related ventral striatal activity was examined.
  
  
  RESULTS
  ADHD patients had higher impulsivity scores and lower ventral striatal activity than healthy comparison subjects. The association between the short allele and increased impulsivity was confirmed. However, independent of disease status, homozygous carriers of the short allele of NOS1, the ADHD risk genotype, demonstrated higher ventral striatal activity than carriers of the other NOS1 VNTR genotypes.
  
  
  CONCLUSIONS
  The authors suggest that the NOS1 genotype influences impulsivity and its relation with ADHD is mediated through effects on this behavioral trait. Increased ventral striatal activity related to NOS1 may be compensatory for effects in other brain regions.
authors: Department of Psychiatry, Radboud University Nijmegen Medical Centre, Donders Institute for Brain, Cognition and Behaviour, the Netherlands.
authors: Martine
authors: M
authors: Hoogman
authors: Esther
authors: E
authors: Aarts
authors: Marcel
authors: M
authors: Zwiers
authors: Dorine
authors: D
authors: Slaats-Willemse
authors: Marlies
authors: M
authors: Naber
authors: Marten
authors: M
authors: Onnink
authors: Roshan
authors: R
authors: Cools
authors: Cornelis
authors: C
authors: Kan
authors: Jan
authors: J
authors: Buitelaar
authors: Barbara
authors: B
authors: Franke
mesh_terms: D000328:Adult; D000483:Alleles; D001289:Attention Deficit Disorder with Hyperactivity / Q000235:genetics* / Q000503:physiopathology / Q000523:psychology; D001479:Basal Ganglia / Q000503:physiopathology*; D001931:Brain Mapping; D005260:Female; D005838:Genotype; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007175:Impulsive Behavior / Q000235:genetics* / Q000503:physiopathology / Q000523:psychology; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D052248:Nitric Oxide Synthase Type I / Q000235:genetics*; D010641:Phenotype; D020080:Tandem Repeat Sequences
chemical_list: D052248:Nitric Oxide Synthase Type I