Interactive effects of OXTR and GAD1 on envy-associated behaviors and neural responses.

Toshiko Tanaka,Fumichika Nishimura,Masahiko Haruno,Kiyoto Kasai,Minoru Kimura,Chihiro Kakiuchi,Mitsuru Kikuchi

doi:10.1371/journal.pone.0210493

Abstract

Inequity aversion (negative feelings induced by outcome differences between the self and other) plays a key role in human social behaviors. The neurotransmitters oxytocin and GABA have been implicated in neural responses to inequity. However, it remains poorly understood not only how individual genetic factors related to oxytocin and GABA affect the neural mechanisms behind inequity aversion, but also how these genes interact. To address these issues, we examined relationships between genotypes, behavioral decisions and brain activities during the ultimatum game. We identified interactive effects between the polymorphisms of the oxytocin receptor gene (OXTR) and glutamate decarboxylase 1 gene for GABA synthesis (GAD1) on envy aversion (i.e., disadvantageous inequity aversion) and on envy-induced activity in the dorsal ACC (dACC). Thus, our integrated approach suggested interactive genetic effects between OXTR and GAD1 on envy aversion and the underlying neural substrates.

Highlights

Inequity aversion plays a key role in human social behaviors, such as cooperation and donation
We examined the correlation between social value orientation and oxytocin receptor gene (OXTR) single nucleotide polymorphisms (SNPs) and found that only rs53576, an SNP located at the long intron, was significantly correlated with the type of social value orientation
We reported the interactive effect between GABA- and oxytocin-related genes on human envy aversion

Summary

Introduction

Inequity aversion plays a key role in human social behaviors, such as cooperation and donation. Functional magnetic resonance imaging (fMRI) studies have established that many brain regions, including the anterior cingulate cortex (ACC) [1,2,3,4], medial prefrontal cortex (mPFC) [1,5,6], dorsolateral prefrontal cortex (dlPFC) [1,3,7,8,9], insula [1,9], amygdala [2,10,11] and striatum [6,7,11], are involved in inequity aversion. The axons of hypothalamic oxytocin neurons project to several regions associated with inequity aversion, including the amygdala, hippocampus, ACC and mPFC [26]. The administration of oxytocin was found to alter the subjective evaluation of unfairness [28] and money allocation with

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Conclusion