Previous studies suggest that the serotonergic pathway may play an important role in prefrontal cortical (PFC) function. The enzyme monoamino oxidase-A (MAO-A) is primarily involved in serotonin catabolism. The MAO-A gene, harbours a variable number tandem repeat (VNTR) polymorphism with high (MAOA-H) and low (MAOA-L) activity variants. Individuals with the MAOA-H allele present with lower amine concentration, higher response inhibition failure and reduced information processing. We therefore hypothesised that these individuals would present with lower PPI levels and working memory performance.

PPI (85-dB prepulse at 30-, 60-, 120-ms intervals) was assessed in 118 healthy males (MAOA-L group n=41 and MAOA-H group n=77). Subjects’ working memory was assessed with the N-back, a PFC-dependent task. PPI data were analysed with repeated measures ANOVA and the N-Back data were analysed with the Mann-Whitney nonparametric test.

Demographic and startle characteristics were similar between the two genotype groups. Analysis of the PPI data revealed higher PPI levels in the MAOA-L compared to the MAOA-H group in all trial types. In addition, the MAOA-L group had significantly more correct responses in the two-back condition.

Compared to MAOA-L, MAOA-H individuals show lower PPI and worse N-Back performance. These results suggest that the MAO-A VNTR polymorphism is an important determinant of sensorimotor gating and working memory, possibly through a PFC mediated mechanism.