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

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.

Individual differences in envy experienced through perspective-taking involves functional connectivity of the superior frontal gyrus

“…The dorsal ACC has been previously implicated in a range of functions, including reward evaluation, motivation, and conflict (Botvinick, Cohen, & Carter, 2004;Botvinick Todd S Braver et al, 2001;Heilbronner & Hayden, 2016;Shenhav, Cohen, & Botvinick, 2016), and is modulated by threat of self-concept (Moll, Zahn, De Oliveira-Souza, Krueger, & Grafman, 2005) and social pain (Eisenberger, 2012). The involvement of the dorsal ACC during the experience of envy has been substantiated by subsequent studies (Cikara & Fiske, 2013;Jankowski & Takahashi, 2014;Santamaría-García et al, 2017;Tanaka et al, 2019). An additional structure of note is the ventral striatum, a region strongly implicated in the processing of rewards (Haber, 2011), scenarios with a distribution of relative rewards (Bault, Joffily, Rustichini, & Coricelli, 2011;Dvash et al, 2010;Grygolec, Coricelli, & Rustichini, 2012;Kedia, Mussweiler, & Linden, 2014) and the processing of losses and gains for both the self and others (Delgado, Li, Schiller, & Phelps, 2008;Lieberman and Eisenberger, 2009;Zink et al, 2008).…”

The Basis For A Neurobiological-Associative Model of Personality and Group Cohesion: The Evolutionary And System Biological Origins Of Social Exclusion, Hierarchy, and Structure

“…The T-T-C-G-G-G haplotype comprising intronic SNPs rs237917 -rs2268498 -rs4564970 -rs237897 -rs2268495 -rs53576 is associated with increased emotional recognition performance under the influence of oxytocin compared to placebo, and the C-C-G-A-G-A haplotype displayed the opposite pattern. The effects associated with the A allele of rs53576, which has previously been associated with phenotypes including reduced dispositional empathy and increased stress reactivity (Rodrigues et al, 2009), increased jealousy (Tanaka et al, 2019), less sensitive parenting (Bakermans-Kranenburg & van IJzendoorn, 2008), lower self-reported empathic concern (Bachmann et al, 2016), and lower prosocial temperament (Tost et al, 2010) seem to fall almost exclusively on the common C-C-G-A-G-A haplotype.…”

“…One likely explanation is that although A-rs53676 clusters with increased neutral amygdala activity (Luo et al, 2017), while also displaying significantly higher jealousy-related amygdala activity (Tanaka et al, 2019), but nonetheless being associated with significantly increased emotional recognition (Chen et al, 2015), and thus doesn't cluster fully with autism despite significantly reduced right supramarginal gyrus activity similar to what is seen with autism in regard to egocentricity bias (Uzefovsky et al, 2019). However, because A-rs53676 does correlate with increased jealousy (Tanaka et al, 2019), lower empathic concern (Bachmann et al, 2016), less sensitive parenting (Bakermans-Kranenburg & van IJzendoorn, 2008), and lower prosocial temperament (Tost et al, 2010), the SNP clearly leads to differential activity, expression, and/or localization.…”

“…It is possible that the A-rs53676 polymorphism showing "no effect" in the meta-analysis (Bakermans-Kranenburg & van IJzendoorn, 2014), while showing so many individual differences in social bonding interaction in individual studies, may be due to A-rs53676 displaying increased activity in the amygdala and thus increasing fear, which involves oxytocin in both fearful memory formation/salience and fear attenuation (Hasan et al, 2019). Furthermore, this may explain somewhat the increased jealousy (Tanaka et al, 2019) if combined with a reduced capacity to overcome egocentricity bias (Uzefovsky et al, 2019) and thus leads to differential social perception and b#onding. It is clear that the A allele can cause differential downstream activation and potentially alters the relative activity of downstream receptor signalling, potentially altering expression in certain types of neurons.…”

Association between arginine vasopressin receptor 1A ( AVPR1A ) polymorphism and inequity aversion

“…Although much research has been conducted on the association between inequity aversion and brain function, little has been conducted on the related genetic factors. One study examined the relationships between inequity aversion and oxytocin receptor (OXTR) and gamma-aminobutyric acid-related genes [24], but no other related studies have been conducted. Since inequity aversion is not a human-specific preference [25][26][27][28][29], DIA and AIA have possibly been endowed in humans and other animals through evolution.…”