An interaction between oxytocin and a genetic variation of the oxytocin receptor modulates amygdala activity toward direct gaze: evidence from a pharmacological imaging genetics study

Abstract

The neuropeptide oxytocin plays an important role in social cognition. One valuable tool to study social cognition in healthy and autistic humans in a neuroscientific context is the investigation of gaze toward another person. Of importance, it has been demonstrated that pronounced amygdala activation could be observed, when participants are confronted with direct gaze pictures in an fMRI setting, an effect that can be particularly observed in autistic individuals. In the present study, a combined pharmacological imaging genetics study has been conducted to further investigate the biological basis of direct gaze processing. N = 55 healthy males were invited to an oxytocin challenge study administered while watching direct vs. averted gaze pictures in an fMRI setting. In addition, the promoter region of the oxytocin receptor (OXTR) gene of the participants was investigated to search for individual differences in the recorded BOLD signal. The main result revealed that a genetic variation of the OXTR gene (rs401015) modulated the right amygdala activity for the fMRI contrast "direct > averted gaze" under the influence of the neuropeptide oxytocin. Here, carriers of the heterozygous CT variant showed higher activity compared to the TT group. The present study highlights the role of individual differences in a genetic variant of the OXTR gene for amygdala activation during processing of direct gaze pictures after intranasal oxytocin administration. In sum, the study shows the importance of combining a pharmacological challenge with genetic imaging to better understand the biological basis of social cognition.