background Attention deficit hyperactivity disorder (adhd) is a common neuropsychiatric and highly heritable disorder. Understanding the modes of action of genes currently known to contribute to disease risk can aid in further unraveling the biological mechanisms underlying adhd. The nos1 gene encoding nitric oxide synthase is a candidate gene for adhd and has been previously linked with impulsivity.
aim To investigate the effect of a functional variable number of tandem repeat in nos1 (Ex1f-vntr) on one of the cognitive deficits in adhd, the processing of rewards.
method A sample of 136 participants, consisting of 87 adult adhd patients and 49 healthy controls, completed a reward-related impulsivity task, i.e. the Delay Discounting Task. One hundred four participants also underwent functional magnetic resonance imaging during a reward anticipation task. The effect of the nos1 Ex1f-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 controls. The association between the short allele and increased impulsivity was confirmed. Independent of disease status, subjects homozygous for the short allele of nos1, the adhd risk genotype, displayed higher ventral striatal activity (p = .001) than did subjects with the other nos1 vntr genotypes.
conclusion We conclude that nos1 influences impulsivity, and that its relation with adhd is mediated through effects on this trait. The current approach and resulting data aid in the understanding of neurobiological substrates of adhd and help to elucidate how adhd susceptibility genes increase disease risk.