The effect of a functional NOS1 promoter polymorphism on impulsivity is moderated by platelet MAO activity.

Rationale: Platelet monoamine oxidase (MAO) activity is associated with impulsivity in clinical samples. Recently, a functional promoter polymorphism of neuronal nitric oxide synthase (NOS1) termed NOS1 ex1f-VNTR was found to have an effect on impulsivity-related traits and resulting psychopathology.

Objective: The study aims to explore the effect of both platelet MAO activity and NOS1 ex1f-VNTR genotype on impulsivity in a population-derived sample.

Methods: This study was on a non-clinical sample of adult male subjects, previously used to investigate the effect of platelet MAO activity on impulsivity-related behaviour (Paaver et al., Psychopharmacology 186:32-40, 2006). Six hundred thirty-seven male subjects were genotyped for the NOS1 ex1f-VNTR promoter polymorphism. Impulsivity was self-reported. Effects of age and smoking, known to affect platelet MAO activity, were controlled for.

Results: No main effect of either NOS1 genotype or platelet MAO activity was present. However, significant interactions were found between effects of the NOS1 genotype and platelet MAO activity on impulsivity measures. Impulsivity and in particular the aspects of adaptive impulsivity (e.g. fast decision-making and excitement-seeking behaviour) were higher in subjects with the NOS1 ex1f-VNTR short/short genotype if they belonged to the platelet MAO medium activity (interquartile) range.

Conclusions: This study supports evidence for higher impulsivity in the NOS1 short/short genotype subjects and further suggests that this is present in the subset of subjects who have close to average platelet MAO activity.