NOS1 ex1f-VNTR polymorphism affects prefrontal oxygenation during response inhibition tasks.

Impulsivity is a trait shared by many psychiatric disorders and therefore a suitable intermediate phenotype for their underlying biological mechanisms. One of the molecular determinants involved is the NOS1 ex1f-VNTR, whose short variants are associated with a variety of impulsive behaviors. Fifty-six healthy controls were stratified into homozygous long (LL) (30 probands) and short (SS) (26 probands) allele groups. Subjects completed a combined stop-signal go/nogo task, while the oxygenation in the prefrontal cortex was measured with functional near-infrared spectroscopy. Electromyography was recorded to control for differences in muscle activity in the two inhibition tasks. Two questionnaires on impulsive traits were completed. Differences between the two tasks are shown by distinct activation patterns within the prefrontal cortex. The nogo task resulted mainly in the activation of the dorsolateral prefrontal cortex (dlPFC), whereas successful and unsuccessful inhibition in the stop-signal task elicited the predicted activity in the inferior frontal cortex (IFC). Although significant differences were found in neither the scores obtained on impulsivity-related questionnaires nor the behavioral data, the LL group displayed increased dlPFC activity during nogo trials and the predicted activation in the IFC during successful inhibition in the stop-signal task, while no significant activation was found in the SS group. Our data confirm an influence of NOS1 ex1f-VNTR on impulsivity, as carriers of the short risk allele exhibited diminished activity of (pre-)frontal brain regions during the inhibition in a stop-signal task. Impairment of prefrontal control with consecutive failure of inhibitory processes might underlie association findings reported previously.