Paradoxical association of the brain-derived-neurotrophic-factor val66met genotype with response inhibition

Abstract

Response inhibition is a basic executive function which is dysfunctional in various basal ganglia diseases. The brain-derived-neurotrophic-factor (BDNF) plays an important pathophysiological role in these diseases. In the current study we examined the functional relevance of the BDNF val66met polymorphism for response inhibition processes in 57 healthy human subjects using event-related potentials (ERPs), i.e. the Nogo-N2 and Nogo-P3, which likely reflect different aspects of inhibition. Our results support the pre-motor inhibition theory of the Nogo-N2. We show that the BDNF val66met polymorphism selectively modulates the Nogo-N2. Response inhibition was better in the val/met–met/met group, since this group committed fewer false alarms, and their Nogo-N2 was larger, compared to the val/val group. This is the first study showing that met alleles of the BDNF val66met polymorphism confer an advantage for a specific cognitive function. We propose a neuronal model how this advantage gets manifest on a neuronal level.