Interaction effects of the 5-HTT and MAOA-uVNTR gene variants on pre-attentive EEG activity in response to threatening voices

Both the serotonin transporter polymorphism ( 5-HTTLPR ) and the monoamine oxidase A gene ( MAOA-uVNTR ) are considered genetic contributors for anxiety-related symptomatology and aggressive behavior. Nevertheless, an interaction between these genes and the pre-attentive processing of threatening voices –a biological marker for anxiety-related conditions– has not been assessed yet. Among the entire sample of participants in the study with valid genotyping and electroencephalographic (EEG) data (N = 140), here we show that men with low-activity MAOA-uVNTR , and who were not homozygous for the 5- HTTLPR short allele (s) (n = 11), had significantly larger fearful MMN amplitudes –as driven by significant larger ERPs to fearful stimuli– than men with high-activity MAOA-uVNTR variants (n = 20). This is in contrast with previous studies, where significantly reduced fearful MMN amplitudes, driven by increased ERPs to neutral stimuli, were observed in those homozygous for the 5- HTT s-allele. In conclusion, using genetic, neurophysiological, and behavioral measurements, this study illustrates how the intricate interaction between the 5-HTT and the MAOA-uVNTR variants have an impact on threat processing, and social cognition, in male individuals (n = 62).