The oxytocin receptor gene (OXTR) in relation to state levels of loneliness in adolescence: evidence for micro-level gene-environment interactions.
ABSTRACT: 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.
Project description:The single nucleotide polymorphism rs53576 of the oxytocin receptor (OXTR) gene is involved in forming and maintaining relationships in various social contexts. However, this has not been studied in the childhood peer context. The present study followed 359 children (51.6% girls) from age 9 to 12 to explore associations between OXTR rs53576 genotype (i.e., AA, AG or GG genotype) and three indicators of children's relationships with peers: likability and dis-likability among, and friendship with, classroom peers. Our results showed that OXTR rs53576 was associated with likability among boys, but not with dis-likability and friendship or among girls. Boys with an A and a G allele (i.e., AG genotype) became increasingly more liked by their peers across the four-year studied period than those with two A alleles or two G alleles (i.e., AA and GG genotype). This study indicates that OXTR rs53576 genotype might influence children's peer relationships, particularly their likeability among peers. Associations between OXTR rs53576 and peer relationships may differ depending on children's sex and the specific type of peer-relationship under scrutiny.
Project description:Previous studies have shown that genetic variations in rs53576, a common variant of the oxytocin receptor gene (OXTR) resulting from a single nucleotide polymorphism involving an adenine (A)/guanine (G) transition, are associated with attitudinal trust in men. However, the pathway from gene to behaviour has not been elucidated. We conducted the present study to determine whether amygdala volume mediates the association between OXTR rs53576 genotypes and attitudinal trust. Our results revealed that the left amygdala volume was significantly smaller in GG men than in AA and AG men, whereas it was significantly smaller in AA and AG women than in GG women. In addition, the left amygdala volume was negatively associated with attitudinal trust in men, whereas there was no such association in women. We also found a significant mediation effect of the left amygdala volume on the association between OXTR rs53576 genotypes and attitudinal trust in men. The results of our study suggest that the left amygdala volume plays a pivotal role in the association between OXTR rs53576 genotypes and attitudinal trust in men.
Project description:Background: To understand the genetic underpinnings of emotion, researchers have studied genetic variants in the oxytocin system, a hormone and neurotransmitter important to socio-emotional functioning. The oxytocin receptor gene (OXTR) variant rs53576 has been associated with emotional traits such as positive affect and related constructs such as optimism and self-esteem. Individuals carrying the A allele (AG and AA genotypes) of rs53576 have been found to score lower in these traits when compared to GG homozygotes, although not always. Given recent mixed evidence regarding this polymorphism, replication of these associations is critical. Methods: Using a cross-sectional design, the present study tested the association between rs53576 and a wide variety of emotional traits and states in a sample of 611 young adults ages 18 - 25 of various ethnicities (European, Asian, M?ori/Pacific Islander, other). Participants completed standard trait measures of positive and negative affect, depressive symptoms, life engagement, psychological well-being, optimism, and self-esteem. They also completed state measures of positive and negative affect and life engagement for 13-days using Internet daily diaries. Results: Controlling for ethnicity and gender, variation at the OXTR variant rs53576 obtained from blood samples was not related to any of the emotional traits or states. This null finding occurred despite measuring emotions in "near to real time" using daily diaries and having sufficient power to detect a medium effect size difference between homozygous genotype groups. Conclusion: These findings suggest that variation at the rs53576 locus may not be as involved in emotional differences as initial studies suggested.
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:<h4>Background</h4>It is assumed that the oxytocin receptor gene (OXTR) is associated with factors that are related to features of reproduction as well as the currently emerging fields of mood and emotional response.<h4>Methods</h4>We analysed data from over 8000 mothers who participated in the Avon Longitudinal Study of Parents and Children (ALSPAC). We determined reproductive, emotional and personality differences related to the two SNPs rs53576 and rs2254298 of the oxytocin receptor gene to determine whether there was evidence in this population for: (i) associations with emotional and personality differences, and (ii) behavioural or environmental links with these SNPs using a hypothesis free approach with over 1000 types of exposure.<h4>Results</h4>Our analyses of 7723 women showed that there were no differences in 11 mood, social or relationship characteristics associated with the rs2254298, and just one with rs53576 (with emotional loneliness)--one statistically significant out of 22 tests is no more than would be expected by chance. There were no interactions with childhood abuse. Using a hypothesis-free approach we found few indicators of environmental or behavioural differences associated with rs2254298, but there was an excess of associations with eating habits with rs53576. The findings included an association with dieting to lose weight, and habits typical of bulimia for the women with GG. The nutrition of the women also showed negative associations of the GG genotype with 13 nutrients, including vitamins D, B12 and retinol, and intake of calcium, potassium and iodine.<h4>Conclusions</h4>We conclude that this large database of pregnant women was unable to provide confirmation of the types of personality associated with these two OXTR SNPs, but we have shown some evidence of eating differences in those with GG on rs53576. Confirmation of our hypothesis free associations using other data sets is important.
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:Not much is known regarding underlying biological pathways to adolescents' loneliness. Insight in underlying molecular mechanisms could inform intervention efforts aimed at reducing loneliness. Using latent growth curve modeling, baseline levels and development of loneliness were studied in two longitudinal adolescent samples. Genes (OXTR, OXT, AVPR1A, AVPR1B) were examined using SNP-based, gene-based, and polygenic risk score (PRS) approaches. In both samples, SNP- and gene-based tests showed involvement of the OXTR gene in development of loneliness, though, significance levels did not survive correction for multiple testing. The PRS approach provided no evidence for relations with loneliness. We recommend alternative phenotyping methods, including environmental factors, to consider epigenetic studies, and to examine possible endophenotypes in relation to adolescents' loneliness.
Project description:A common variant in the oxytocin receptor gene (OXTR), rs53576, has been broadly linked to socially related personality traits and behaviors. However, the pattern of published results is inconsistent. Here, we performed a meta-analysis to comprehensively evaluate the association. The literature was searched for relevant studies and effect sizes between individuals homozygous for the G allele (GG) and individuals with A allele carriers (AA/AG). Specifically, two indices of sociality were evaluated independently: i) general sociality (24 samples, n = 4955), i.e., how an individual responds to other people in general; and ii) close relationships (15 samples, n = 5262), i.e., how an individual responds to individuals with closed connections (parent-child or romantic relationship). We found positive association between the rs53576 polymorphism and general sociality (Cohen's d = 0.11, p = .02); G allele homozygotes had higher general sociality than the A allele carriers. However, the meta-analyses did not detect significant genetic association between rs53576 and close relationships (Cohen's d = 0.01, p = .64). In conclusion, genetic variation in the rs53576 influences general sociality, which further implies that it is worthy to systematically examine whether the rs53576 is a valid genetic marker for socially related psychiatric disorders.
Project description:BACKGROUND:Environmental effects and personal experiences could be expressed in individuals through epigenetic non-structural changes such as DNA methylation. This methylation could up- regulate or down-regulate corresponding gene expressions and modify related phenotypes. DNA methylation increases with aging and could be related to the late expression of some forms of mental disease. The objective of this study was to evaluate the association between anxiety disorders and/or depression in older women and DNA methylation for four genes related to anxiety or depression. METHODS:Women aged 65 and older with (n = 19) or without (n = 24) anxiety disorders and/or major depressive episode (DSM-IV), were recruited. DNA methylation and single nucleotide variant (SNV) were evaluated from saliva, respectively by pyrosequencing and by PCR, for the following genes: brain-derived neurotrophic factor (BDNF; rs6265), oxytocin receptor (OXTR; rs53576), serotonin transporter (SLC6A4; rs25531), and apolipoprotein E (APOE; rs429358 and rs7412). RESULTS:A greater BDNF DNA methylation was observed in subjects with anxiety/depression compared to control group subjects (Mean: 2.92 SD ± 0.74 vs. 2.34 ± 0.42; p= 0.0026). This difference was more pronounced in subjects carrying the BDNF rs6265 CT genotype (2.99 ± 0.41 vs. 2.27 ± 0.26; p= 0.0006) than those carrying the CC genotype (p= 0.0332); no subjects with the TT genotype were observed. For OXTR, a greater DNA methylation was observed in subjects with anxiety/depression, but only for those carrying the AA genotype of the OXTR rs53576 SNV, more particularly at one out of the seven CpGs studied (7.01 ± 0.94 vs. 4.44 ± 1.11; p= 0.0063). No significant differences were observed for APOE and SLC6A4. CONCLUSION:These results suggest that DNA methylation in interaction with SNV variations in BDNF and OXTR, are associated with the occurrence of anxiety/depression in older women.
Project description:Oxytocin (OT) and a polymorphism (rs53576) in the oxytocin receptor gene (OXTR) have been independently associated with stress reactivity, whereas oxytocin's sister peptide, arginine vasopressin (AVP) and polymorphisms in the vasopressin receptor gene (AVPR1A) have been independently associated with aggressive behavior. In this study, 68 men and 98 women were genotyped for the OXTR rs53576 polymorphism and the AVPR1A RS1 polymorphism. Baseline and poststressor levels of plasma OT, plasma AVP, positive affect, and anger were assessed. Women, but not men, with high levels of poststressor OT and the GG genotype of rs53576 felt the most positive affect after the stressor. Men, but not women, with high levels of poststressor AVP and the 320 allele of the RS1 polymorphism reported more poststressor anger than noncarriers. These data constitute the first evidence that oxytocin and vasopressin receptor genes interact with levels of OT and AVP to predict sex-specific emotional stress responses.