Affective Language, Interpretation Bias and Its Molecular Genetic Variations: Exploring the Relationship Between Genetic Variations of the OXTR Gene (rs53576 and rs2268498) and the Emotional Evaluation of Words Related to the Self or the Other.
ABSTRACT: Several studies have demonstrated links between oxytocin and socio-emotional information processing. Regarding the frequently studied single nucleotide polymorphism (SNP) rs53576 and the less studied, functional polymorphism rs2268498 of the oxytocin receptor (OXTR) gene, previous research suggested that their variants might be associated with different proficiency in the processing of social information. Differences between the genotype variants are not restricted to non-verbal stimulus processing but have also been reported in the verbal domain. Moreover, there is evidence that oxytocin expression influences empathic communication and language development during childhood, indicating that language-based theory-of-mind abilities may be affected by interindividual differences in OXTR genotypes as well. The present study therefore investigates whether two prominent SNPs of the OXTR gene (rs53576 GG vs. A+; rs2268498 TT vs. C+) also play a role in the affective evaluation of verbal stimuli varying in emotional valence and in self-other reference. Participants (N = 149 Caucasian participants, 104 females; A+: n = 80, GG: n = 69; C+: n = 98, TT: n = 51) were presented a series of written, self-, other-, and unreferenced words of positive, negative, and neutral valence and asked to affectively evaluate each word pair as positive, negative, or neutral by button press. In line with previous research, reaction times and accuracy (number of valence-congruent responses) showed a self-positivity bias (i.e., preferential processing of self-related positive words), which, however, was unaffected by participants' genotype. Regarding affective evaluation of neutral words (interpretation bias), A+ carriers displayed a weaker positive interpretation bias compared to GG carriers in the other- and unreferenced stimulus categories. C+ carriers showed a weaker positive interpretation bias than TT carriers in the self-reference condition and in the other-reference condition. These effects were independent from participants' gender. The present results suggest that the OXTR genotype and hence participants' genetic oxytocin sensitivity may cause an interpretation bias in the spontaneous appraisal of neutral words.
Project description:The neuromodulators oxytocin and serotonin have been implicated in regulating affective processes underlying empathy. Understanding this dependency, however, has been limited by a lack of objective metrics for measuring empathic performance. Here we employ a novel psychophysical method for measuring empathic performance that quantitatively measures the ability of subjects to decode the experience of another person's pain. In 50 female subjects, we acquired functional magnetic resonance imaging data as they were exposed to a target subject experiencing variable degrees of pain, whilst performing an irrelevant attention-demanding task. We investigated the effect of variation in the oxytocin receptor gene (OXTR) and the serotonin transporter gene (SLC6A4) on the psychophysical and neurometric variability associated with empathic performance. The OXTR rs2268498 and rs53576 polymorphisms, but not the SLC6A4 5-HTTLPR, were associated with significant differences in empathic accuracy, with CC- and AA-carriers, respectively, displaying higher empathic accuracy. For OXTR rs2268498 there was also a genotype difference in the correlation between empathic accuracy and activity in the superior temporal sulcus (STS). In OXTR rs2268498 CC-carriers, high empathic accuracy was associated with stronger responsiveness of the right STS to the observed pain. Together, the results show that genetic variation in the OXTR has significant influence on empathic accuracy and that this may be linked to variable responsivity of the STS.
Project description:Empathic neural responses to others' suffering are subject to both social and biological influences. The present study tested the hypothesis that empathic neural responses to others' pain are more flexible in an intergroup context in G/G than A/A carriers of the oxytocin receptor gene (OXTR) (rs53576). We recorded event-related brain potentials to painful vs neutral expressions of Asian and Caucasian faces that were assigned to a fellow team or an opponent team in Chinese carriers of G/G or A/A allele of OXTR. We found that G/G carriers showed greater neural responses at 136-176 ms (P2) over the frontal/central region to painful vs neutral expressions of faces with shared either racial or mini group identity. In contrast, A/A carriers showed significant empathic neural responses in the P2 time window only to the faces with both shared racial and mini group identity. Moreover, the racial in-group bias in empathic neural responses varied across individuals' empathy traits and ethnic identity for G/G but not A/A carriers. Our findings provide electrophysiological evidence for greater flexibility of empathic neural responses in intergroup contexts in G/G (vs A/A) carriers of OXTR and suggest interactions between OXTR and intergroup relationships on empathy for others' suffering.
Project description:Oxytocin receptor (OXTR) gene polymorphisms are related to individual differences in emotional processing of social cues. However, whether OXTR polymorphisms affect emotional processing of nonsocial cues remains unclear. The present study investigated the relationship between the OXTR rs53576 polymorphism and emotional processing of social cues and nonsocial cues.Event-related potentials were recorded from 88 male participants while images of humans and images of objects were presented as social cues and nonsocial cues, respectively.First, the results showed that GG carriers of OXTR rs53576 showed more negative N1 (50-200 ms) than AA carriers in response to images of both humans and objects. Second, GG carriers showed more negative N2 (200-320 ms) than AA carriers in response to images of humans but not in response to images of objects. Third, GG carriers showed more negative N2 in response to images of humans than images of objects, whereas AA carriers showed the opposite pattern. Fourth, we observed no difference in late positive potential (600-1000 ms) to images of humans or objects that depended on the OXTR rs53576 polymorphism.These results suggest that the OXTR rs53576 polymorphism affects emotional processing of not only social cues but also nonsocial cues in the very early stage (reflected in N1); however, the data also suggest that the OXTR rs53576 polymorphism is related specifically to increased emotional processing of social cues in the middle stage (reflected in N2).
Project description:Methylenedioxymethamphetamine (MDMA) increases oxytocin, empathy, and prosociality. Oxytocin plays a critical role in emotion processing and social behavior and has been shown to mediate the prosocial effects of MDMA in animals. Genetic variants, such as single-nucleotide polymorphisms (SNPs), of the oxytocin receptor (OXTR) may influence the emotional and social effects of MDMA in humans. The effects of common genetic variants of the OXTR (rs53576, rs1042778, and rs2254298 SNPs) on the emotional, empathogenic, and prosocial effects of MDMA were characterized in up to 132 healthy subjects in a pooled analysis of eight double-blind, placebo-controlled studies. In a subset of 53 subjects, MDMA produced significantly greater feelings of trust in rs1042778 TT genotypes compared with G allele carriers. The rs53576 and rs225498 SNPs did not moderate the subjective effects of MDMA in up to 132 subjects. None of the SNPs moderated MDMA-induced impairments in negative facial emotion recognition or enhancements in emotional empathy in the Multifaceted Empathy Test in 69 subjects. MDMA significantly increased plasma oxytocin concentrations. MDMA and oxytocin concentrations did not differ between OXTR gene variants. The present results provide preliminary evidence that OXTR gene variations may modulate aspects of the prosocial subjective effects of MDMA in humans. However, interpretation should be cautious due to the small sample size. Additionally, OXTR SNPs did not moderate the subjective overall effect of MDMA (any drug effect) or feelings of "closeness to others". TRIAL REGISTRATION:ClinicalTrials.gov: http://www.clinicaltrials.gov, No: NCT00886886, NCT00990067, NCT01136278, NCT01270672, NCT01386177, NCT01465685, NCT01771874, and NCT01951508.
Project description:Recent evidence suggests that the association between oxytocin receptor polymorphism (OXTR rs53576) and emotion-related behavioral/psychological tendencies differs between individuals from East Asian and Western cultures. What remains unresolved is which specific dimension of cultural orientations interacts with OXTR rs53576 to shape these tendencies and whether such gene × culture interactions occurs at both behavioral and neural level. This study investigated whether and how OXTR rs53576 interacts with interdependence-a key dimension of cultural orientations that distinguish between East Asian and Western cultures-to affect human empathy that underlies altruistic motivation and prosocial behavior. Experiment 1 measured interdependence, empathy trait and OXTR rs53576 genotypes of 1536 Chinese participants. Hierarchical regression analyses revealed a stronger association between interdependence and empathy trait in G allele carriers compared with A/A homozygotes of OXTR rs53576. Experiment 2 measured neural responses to others' suffering by scanning A/A and G/G homozygous of OXTR rs53576 using functional magnetic resonance imaging. Hierarchical regression analyses revealed stronger associations between interdependence and empathic neural responses in the insula, amygdala and superior temporal gyrus in G/G compared with A/A carriers. Our results provide the first evidence for gene × culture interactions on empathy at both behavioral tendency and underlying brain activity.
Project description:Recent research indicates that the neuropeptide oxytocin and the gene for the oxytocin receptor (OXTR) have been implicated in the modulation of various social behaviors, including those related to empathy and sensitivity to others. In this study, we examine the hypothesis that genetic variation in OXTR is associated with autonomic reactions when perceiving others in distress. We also explore the possibility that individual disposition in empathic concern would differ by OXTR genotype. To address these questions, 51 male participants (18-35 years of age), genotyped for OXTR rs53576, viewed a social interaction containing high levels of individual distress and apparent physical pain. Electrodermal activity, a measure of sympathetic nervous system activity, was collected during the presentation of the stimuli. Participants also completed a self-report dispositional measure of empathy prior to starting the study and provided ratings of arousal while viewing the stimuli. OXTR variant rs53576 GG individuals showed increased levels of sympathetic and subjective arousal in response to the stimuli compared to A allele carriers. GG homozygotes also expressed greater levels of empathic concern. These findings support the importance of the oxytocin receptor variation in emotional and physiological reactions to the affective experiences of other conspecifics.
Project description:The oxytocin receptor gene (OXTR) influences human behavior. The G allele of OXTR rs53576 has been associated with both prosocial and maladaptive behaviors but few studies have taken account of environmental factors. The present study determined whether the association of childhood maltreatment with conduct problems was modified by OXTR rs53576 genotypes. In a general population sample of 1591 teenagers, conduct problems as well as maltreatment were measured by self-report. DNA was extracted from saliva samples. In males, there was a significant positive association between maltreatment and conduct problems independent of the genotype. In females, among G allele carriers, the level of conduct problems was significantly higher among those who had been maltreated as compared to those not maltreated. By contrast, among female AA carriers, conduct problems did not vary between those who were, and who were not, maltreated. The results indicate that OXTR rs53576 plays a role in antisocial behavior in females such that the G allele confers vulnerability for antisocial behavior if they experience maltreatment, whereas the A allele has a protective effect.
Project description:RATIONALE:Oxytocin is a neuropeptide that is associated with increases in social affiliative behaviors, particularly toward infants. However, no previous study has investigated healthy adults' responses to infant faces following oxytocin administration. In addition, given that preliminary evidence suggests that a single-nucleotide polymorphism of the oxytocin receptor (OXTR) gene, rs53576, may influence behaviors associated with parental sensitivity, we assessed whether such responses vary according to OXTR rs53576 genotype. OBJECTIVES:The present study assessed the effects of intranasally administered oxytocin and OXTR genotype on human adults' preferences for infant faces. METHODS:A double-blind, between-groups design was used, with 57 genotyped volunteers randomly assigned to receive intranasally administered oxytocin or placebo. Fifty minutes following the administration of oxytocin or placebo, participants viewed infants' and adults' faces showing neutral expressions and assessed how appealing they found each face. RESULTS:Infants' faces were more strongly preferred following oxytocin inhalation relative to placebo. When participants were separated according to genotype, this effect was only observed for participants homozygous for the rs53576G allele. Parallel effects were not seen for adults' faces. CONCLUSIONS:The present results are consistent with the hypothesis that acute oxytocin administration increases sensitivity to reward-relevant features of infants and/or reduces sensitivity to their aversive properties. The results are also consistent with suggestions of more efficient oxytocinergic function in rs53576G homozygotes.
Project description:3,4-Methylenedioxymethamphetamine (MDMA, "ecstasy") enhances desire to socialize and feelings of empathy, which are thought to be related to increased oxytocin levels. Thus, variation in the oxytocin receptor gene (OXTR) may influence responses to the drug. Here, we examined the influence of a single OXTR nucleotide polymorphism (SNP) on responses to MDMA in humans. Based on findings that carriers of the A allele at rs53576 exhibit reduced sensitivity to oxytocin-induced social behavior, we hypothesized that these individuals would show reduced subjective responses to MDMA, including sociability. In this three-session, double blind, within-subjects study, healthy volunteers with past MDMA experience (N = 68) received a MDMA (0, 0.75 mg/kg, and 1.5 mg/kg) and provided self-report ratings of sociability, anxiety, and drug effects. These responses were examined in relation to rs53576. MDMA (1.5 mg/kg) did not increase sociability in individuals with the A/A genotype as it did in G allele carriers. The genotypic groups did not differ in responses at the lower MDMA dose, or in cardiovascular or other subjective responses. These findings are consistent with the idea that MDMA-induced sociability is mediated by oxytocin, and that variation in the oxytocin receptor gene may influence responses to the drug.
Project description:Previous research has shown that the rs53576 variant of the oxytocin receptor gene (OXTR) is associated with trait levels of loneliness, but results are inconsistent. The aim of the present study is to examine micro-level effects of the OXTR rs53576 variant on state levels of loneliness in early adolescents. In addition, gene-environment interactions are examined between this OXTR variant and positive and negative perceptions of company. Data were collected in 278 adolescents (58% girls), by means of the Experience Sampling Method (ESM). Sampling periods consisted of six days with nine assessments per day. A relation was found between the OXTR rs53576 variant and state loneliness, in girls only. Girls carrying an A allele had higher levels of state loneliness than girls carrying the GG genotype. In addition, adolescents with an A allele were more affected by negative perceptions of company than GG carriers, on weekend days only. No significant gene-environment interactions were found with positive company. Adolescents carrying an A allele were more susceptible to negative environments during weekend days than GG carriers. Our findings emphasize the importance of operationalizing the phenotype and the environment accurately.