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

Martinez, Liao and colleagues investigate the processing of fearful stimuli in individuals with variations in genes linked to serotonergic brain function. They find evidence of an interaction between these variations and the pre-attentive processing of those stimuli.

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).