Methylation of OXT and OXTR genes, central oxytocin, and social behavior in female macaques.
Ontology highlight
ABSTRACT:
SUBMITTER: De Leon D
PROVIDER: S-EPMC7725942 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:Oxytocin is a key modulator of emotional processing and social cognitive function. In line with this, polymorphisms of genes involved in oxytocin signaling, like the oxytocin receptor (OXTR) gene, are known to influence social behavior in various species. However, to date, no study has investigated environmental factors possibly influencing the epigenetic variation of the OXTR gene and its behavioral effects in dogs. Pet dogs form individualized and strong relationships with their owners who are central figures in the social environment of their dogs and therefore might influence the methylation levels of their OXTR gene. Here we set out to investigate whether DNA methylation within the OXTR promoter region of pet dogs is linked to their owner's interaction style and to the social behavior of the dogs. To be able to do so, we collected buccal epithelial cells and, in Study 1, we used pyrosequencing techniques to look for differentially methylated CpG sites in the canine OXTR promoter region on a heterogeneous sample of dogs and wolves of different ages and keeping conditions. Four identified sites (at positions -727, -751, -1371, and -1383 from transcription start site) showing more than 10% methylation variation were then, in Study 2, measured in triplicate in 217 pet Border Collies previously tested for reactions to an adverse social situation (i.e., approach by a threatening human) and with available data on their owners' interaction styles. We found that CpG methylation was significantly associated with the behavior of the dogs, in particular with the likelihood that dogs would hide behind their owner or remain passive when approached by a threatening human. On the other hand, CpG methylation was not related to the owners' behavior but to dog sex (at position -1371). Our findings underpin the complex relationship between epigenetics and behavior and highlight the importance of including epigenetic methods in the analysis of dog behavioral development. Further research is needed to investigate which environmental factors influence the epigenetic variation of the OXTR gene.
| S-EPMC5385375 | biostudies-literature
Project description:The neuropeptide oxytocin (OT) has been implicated in a wide range of affiliative processes. OT exerts its functions via OT receptors, which are encoded by the oxytocin receptor gene (OXTR). Epigenetic modification of OXTR through the process of DNA methylation has been associated with individual differences in behavioral phenotypes. Specifically, lower levels of OXTR methylation have been linked to better social and affective functioning. However, research on epigenetic mechanisms of OXTR is scarce in non-clinical populations, and even less is known about epigenetic variability across adulthood. The present study assessed methylation levels at OXTR CpG site -934 and plasma OT levels in 22 young (20-31?years, M?=?23.6) and 34 older (63-80?years, M?=?71.4) participants. Lower levels of OXTR methylation and higher plasma OT levels were associated with less self-reported attachment anxiety in young but not older participants, with largely independent contributions of OXTR methylation and plasma OT levels. In contrast, in the overall sample, lower levels of OXTR methylation were associated with higher self-reported attachment avoidance. Age analysis suggested that these results were largely driven by young adults. Plasma OT levels were unrelated to attachment avoidance. Taken together, these findings support the emerging notion in the literature that epigenetic properties of OXTR, in addition to endogenous OT levels, are related to adult attachment. Further, the age effects observed in the associations between OXTR methylation, plasma OT, and adult attachment emphasize the importance of adopting a developmental perspective when studying properties of the OT system and their relation to affiliative processes. Findings contribute to growing evidence suggesting that epigenetic modification of genes regulating OT pathways and endogenous OT levels are associated with the way people form and maintain intimate social relationships.
| S-EPMC6072619 | biostudies-literature
Project description:The aim of this study was to investigate whether maternal adversities and cortisol levels during pregnancy predict cord blood DNA methylation of the oxytocin receptor (OXTR). We collected cord blood of 39 babies born to mothers participating in a cross-sectional study (N?=?100) conducted in Basel, Switzerland (2007-10). Mothers completed the Inventory of Life Events (second trimester: T2), the Edinburgh Postnatal Depression Scale (EPDS, third trimester: T3), the Trier Inventory of Chronic Stress (TICS-K, 1-3 weeks postpartum) and provided saliva samples (T2, T3) for maternal cortisol profiles, as computed by the area under the curve with respect to ground (AUCg) or increase (AUCi) for the cortisol awakening response (CAR) and for diurnal cortisol profiles (DAY). OXTR DNA methylation was quantified using Sequenom EpiTYPER. The number of stressful life events (P?=?0.032), EPDS score (P?=?0.007) and cortisol AUCgs at T2 (CAR: P?=?0.020; DAY: P?=?0.024) were negatively associated with OXTR DNA methylation. Our findings suggest that distinct prenatal adversities predict decreased DNA methylation in a gene that is relevant for childbirth, maternal behavior and wellbeing of mother and offspring. If a reduced OXTR methylation increases OXTR expression, our findings could suggest an epigenetic adaptation to an adverse early environment.
| S-EPMC5015800 | biostudies-other
Project description:Maternal oxytocin is connected to aspects of parenting including sensitivity, warmth, positive affect, and affectionate touch. Oxytocin receptor gene (OXTR) polymorphisms are associated with circulating oxytocin levels, altered brain activity, and parenting behaviors. This study aimed to replicate prior work on OXTR single-nucleotide polymorphisms (SNPs) rs1042778 and rs53576 in relation to maternal sensitivity, explore associations with other aspects of parenting (i.e., negative parenting), evaluate observational and self-report measures of parenting in relation to OXTR SNPs, and examine whether childhood trauma exposure moderates the relation between OXTR SNPs and parenting. Mothers (N = 100) were observed during 2 teaching interaction tasks with their 7-month-old infant, completed questionnaire and interview measures related to parenting and trauma history, and provided saliva specimens to derive OXTR genotypes. Mothers with OXTR rs1042778 TT genotypes demonstrated lower behavioral sensitivity, lower engagement, higher intrusiveness, and more frequent frightened/frightening behavior than mothers with TG or GG genotypes. Genotype interacted with childhood trauma history such that mothers who had experienced childhood trauma were more likely to demonstrate frightened/frightening behavior if they had the TT genotype on rs1042778 relative to the TG or GG genotype; however, small cell sizes for this interaction suggest replication is warranted. Contrary to expectations, mothers with the TT genotype on rs1042778 self-reported that they had less impaired bonding than mothers with TG or GG genotypes. Results are discussed with respect to prior work with oxytocin in lower versus higher risk samples, and the potential role of mothers' self-awareness in explaining discrepancies between results from observational versus self-report measures of parenting. (PsycINFO Database Record (c) 2019 APA, all rights reserved).
| S-EPMC6768723 | biostudies-literature
Project description:BACKGROUND:The neuropeptide Oxytocin (OXT) plays a central role in birthing, mother-infant bonding and a broad range of related social behaviours in mammals. More recently, interest has extended to epigenetic programming of genes involved in oxytocinergic neurotransmission. This review brings together early findings in a rapidly developing field of research, examining relationships between DNA methylation (DNAm) of the Oxytocin Receptor Gene (OXTR) and social and emotional behaviour in human populations. METHOD:A systematic search across Web of Knowledge/Science, Scopus, Medline and EMBASE captured all published studies prior to June 2017 examining the association between OXTR DNAm and human social and emotional outcomes. Search terms included 'oxytocin gene' or 'oxytocin receptor gene' and 'epigenetics' or 'DNA methylation'. Any article with a focus on social and emotional functioning was then identified from this set by manual review. RESULTS:Nineteen studies met eligibility criteria. There was considerable heterogeneity of study populations, tissue samples, instrumentation, measurement, and OXTR site foci. Only three studies examined functional consequences of OXTR DNAm on gene expression and protein synthesis. Increases in OXTR DNAm were associated with callous-unemotional traits in youth, social cognitive deficits in Autistic Spectrum Disorder (ASD), rigid thinking in anorexia nervosa, affect regulation problems, and problems with facial and emotional recognition. In contrast, reductions in DNAm were associated with perinatal stress, postnatal depression, social anxiety and autism in children. CONCLUSIONS:Consistent with an emerging field of inquiry, there is not yet sufficient evidence to draw conclusions about the role of OXTR DNAm in human social and emotional behaviour. However, taken together, findings point to increased OXTR DNAm in general impairments in social, cognitive and emotional functioning, and decreased OXTR DNAm in specific patterns of impairment related to mood and anxiety disorders (but not in all). Future progress in this field would be enhanced by adequately powered designs, greater phenotypic precision, and methodological improvements including longitudinal studies with multiple time-points to facilitate causal inference.
| S-EPMC5975530 | biostudies-literature
Project description:Findings of studies investigating OXTR SNP rs53576 (G-A) variation in social behavior have been inconsistent, possibly because DNA methylation after stress exposure was eliminated from consideration. Our goal was to examine OXTR rs53576 allele-specific sensitivity for neonatal OXTR DNA methylation in relation to (1) a prenatal maternal stress composite, and (2) child autistic traits. Prospective data from fetal life to age 6 years were collected in a total of 743 children participating in the Generation R Study. Prenatal maternal stress exposure was uniquely associated with child autistic traits but was unrelated to OXTR methylation across both OXTR rs53576 G-allele homozygous children and A-allele carriers. For child autistic traits in general and social communication problems in particular, we observed a significant OXTR rs53576 genotype by OXTR methylation interaction in the absence of main effects, suggesting that opposing effects cancelled each other out. Indeed, OXTR methylation levels were positively associated with social problems for OXTR rs53576 G-allele homozygous children but not for A-allele carriers. These results highlight the importance of incorporating epi-allelic information and support the role of OXTR methylation in child autistic traits. Autism Res 2017, 10: 430-438. © 2016 International Society for Autism Research, Wiley Periodicals, Inc.
| S-EPMC5426537 | biostudies-literature
Project description:BackgroundOxytocin (OXT) has been implicated in a suite of complex social behaviors including observed choices in economic laboratory experiments. However, actual studies of associations between oxytocin receptor (OXTR) gene variants and experimentally elicited social preferences are rare.Methodology/principal findingsWe test hypotheses of associations between social preferences, as measured by behavior in two economic games, and 9 single nucleotide polymorphisms (SNPs) of the OXTR gene in a sample of Swedish twins (n = 684). Two standard economic games, the dictator game and the trust game, both involving real monetary consequences, were used to elicit such preferences. After correction for multiple hypothesis testing, we found no significant associations between any of the 9 single nucleotide polymorphisms (SNPs) and behavior in either of the games.ConclusionWe were unable to replicate the most significant association reported in previous research between the amount donated in a dictator game and an OXTR genetic variant.
| S-EPMC2886839 | biostudies-literature
Project description:Although positive effects of oxytocin (OT) on social functioning are well-demonstrated, little is known about the mechanisms through which OT may drive early social development, or its therapeutic efficacy in infancy. To address these critical issues, we investigated the effects of exogenous OT on neural (EEG) and behavioral responses during observation of live facial gestures in infant macaques with limited social exposure (i.e. nursery-reared). Three key findings were revealed. First, OT increased alpha suppression over posterior scalp regions during observation of facial gestures but not non-biological movement, suggesting that OT targets self-other matching and attentional cortical networks involved in social perception from very early infancy. Second, OT increased infant production of matching facial gestures and attention towards the most socially-relevant facial stimuli, both behaviors typically silenced by early social deprivation. Third, infants with higher cortisol levels appeared to benefit the most from OT, displaying greater improvements in prosocial behaviors after OT administration. Altogether, these findings suggest that OT promotes prosocial behaviors and associated neural responses likely impacted by early social adversity, and demonstrate the potential of OT administration to ameliorate social difficulties in the context of neurodevelopmental and early-emerging psychiatric disorders, at a developmental stage when brain plasticity is greatest.
| S-EPMC8042434 | biostudies-literature
Project description:Early caregiver-infant interactions are critical for infants' socioemotional and cognitive development. Several hormones and neuromodulators, including oxytocin, affect these interactions. Exogenous oxytocin promotes social behaviors in several species, including human and nonhuman primates. Although exogenous oxytocin increases social function in adults--including expression recognition and affiliation--it is unknown whether oxytocin can increase social interactions in infants. We hypothesized that nebulized oxytocin would increase affiliative social behaviors and such effects would be modulated by infants' social skills, measured earlier in development. We also hypothesized that oxytocin's effects on social behaviors may be due to its anxiolytic effects. We tested these hypotheses in a blind study by nebulizing 7- to 14-d-old macaques (n = 28) with oxytocin or saline. Following oxytocin administration, infants' facial gesturing at a human caregiver increased, and infants' salivary oxytocin was positively correlated with the time spent in close proximity to a caregiver. Infants' imitative skill (measured earlier in development: 1-7 d of age) predicted oxytocin-associated increases in affiliative behaviors--lip smacking, visual attention to a caregiver, and time in close proximity to a caregiver--suggesting that infants with higher propensities for positive social interactions are more sensitive to exogenous oxytocin. Oxytocin also decreased salivary cortisol, but not stress-related behaviors (e.g., scratching), suggesting the possibility of some anxiolytic effects. To our knowledge, this study provides the first evidence that oxytocin increases positive social behaviors in newborns. This information is of critical importance for potential interventions aimed at ameliorating inadequate social behaviors in infants with higher likelihood of developing neurodevelopmental disorder.
| S-EPMC4024859 | biostudies-literature
Project description:Maternal behavior (MB) is observable across mammals and represents an important feature of environmental variation during early postnatal development. Oxytocin (OT) plays a crucial role in MB. Even prior to childbirth, pregnancy induces epigenetic and other downstream changes in the maternal OT-system, likely mediated by the actions of steroid hormones. However, little is known about the nature and consequences of epigenetic modifications in the maternal OT-encoding gene (OXT) during pregnancy. Our study aims to investigate temporal dynamics of OXT promoter DNA methylation (DNAm) throughout pregnancy in predicting MB in humans. In 107 mother-child dyads, maternal OXT DNAm was serially analyzed in whole blood in early, mid and late pregnancy. MB was coded based on standardized mother-child interactions at six months postpartum. After controlling for cellular heterogeneity, race/ethnicity, age, and socioeconomic status, OXT-promoter DNAm exhibited a dynamic profile during pregnancy (b?=?0.026, t=-3.37, p?<?.001), with decreases in DNAm from early to mid-pregnancy and no further change until late pregnancy. Moreover, dynamic DNAm trajectories of the OXT-promoter region predicted MB (intrusiveness) at six months postpartum (b?=?0.006, t?=?2.0, p?<?0.05), with 6% higher OXT DNAm in late pregnancy in intrusive compared to non-intrusive mothers. We here demonstrate that OXT promoter DNAm changes significantly throughout gestation in peripheral blood and that these changes are associated with variability in MB, providing a novel potential biomarker predicting postnatal MB.
| S-EPMC6554513 | biostudies-literature