Oxytocin Receptor Gene Research Articles

Neural and behavioral correlates of individual variability in rat helping behavior: a role for social affiliation and oxytocin receptors.

A prosocial response to others in distress is increasingly recognized as a natural behavior for many social species. While prosocial behavior is more frequently observed towards familiar conspecifics, even within the same social context, some individuals are more prone to help than others. In a rat helping behavior test where animals can release a distressed conspecific trapped inside a restrainer, most rats are motivated and consistently release the trapped rat ('openers'), yet around 30% do not open the restrainer ('non-openers'). To characterize the difference between these populations, behavioral and neural markers were compared between opener and non-opener rats in males and females. Openers showed significantly more social affiliative behavior both before and after door-opening compared to non-openers. Oxytocin receptor mRNA levels were higher in the nucleus accumbens (NAc), but not the anterior insula, of openers. Several transcription control pathways were significantly upregulated in openers' NAc. Chemogenetically inhibiting paraventricular oxytocin neurons did not significantly impair helping, but did reduce sociality measures, indicating that helping does not rely solely on oxytocin signaling. Analysis of brain-wide neural activity based on the immediate-early gene c-Fos in males revealed increased activity in openers in prosocial brain regions compared to non-openers. These include regions associated with empathy in humans (insula, somatosensory, cingulate and frontal cortices), and motivation and reward regions such as the NAc. These findings indicate that prosocial behavior may be predicted by affiliative behavior and activity in the prosocial neural network and provide targets for the investigation of causal mechanisms underlying prosocial behavior.Significance Statement Prosocial behavior is observed in many social species, including rodents, yet the determinants underlying why some animals help and others do not is poorly understood. Here, we show behavioral and neural differences between prosocial and non-prosocial pairs in a rat helping behavior test, with increased social interaction and nucleus accumbens oxytocin receptor gene expression in animals that helped.

Current perspectives on the role of oxytocin receptor (OXTR) gene variants in panic disorder: Associations with the disease liability and separation anxiety

Current perspectives on the role of oxytocin receptor (OXTR) gene variants in panic disorder: Associations with the disease liability and separation anxiety

A comprehensive in silico investigation unravels the structural and functional consequences of non-synonymous single-nucleotide polymorphisms in human OXTR gene

A comprehensive in silico investigation unravels the structural and functional consequences of non-synonymous single-nucleotide polymorphisms in human OXTR gene

Genetic Variants in Oxytocinergic System Genes and Their Association with Postpartum Depression Susceptibility

One of the most frequent forms of maternal morbidity following childbirth is postpartum depression. Postpartum depression (PPD), a disabling condition as a major public health concern, has a significant negative impact on the child’s emotional, mental as well as intellectual development if left undiagnosed and untreated, which can later have long-term complications. The oxytocin system is an excellent candidate gene system in the maternal context. Differences in vulnerability of mothers for the onset of postpartum psychiatric disorders could be influenced by individual differences in the genetic profile of each one. In this original research, we aimed to explore if there are any possible contributions of genetic variation on both the oxytocin receptor gene (OXTR) and the oxytocin gene (OXT) to the occurrence of postpartum depression, aiming to provide the latest evidence and determine which genetic polymorphisms significantly create a susceptibility for this condition. A total of 100 mothers were preliminarily genotyped before they completed the Edinburgh Postnatal Depression Scale Questionnaire (EPDS) at 6 weeks postpartum. DNA was extracted from peripheral blood samples of the participants (N = 100) and evaluated for the oxytocin gene (OXT_rs2740210; OXT_rs4813627) and oxytocin receptor gene (OXTR_ rs237885) single nucleotide polymorphisms. The results highlighted a significant interaction between the oxytocin OXT_rs2740210 genotype and maternal postpartum depression in mothers with the CC genotype but not in those with AA/AC genotypes. This reveals that an interaction of vulnerable genotypes (CC genotype of OXT_rs2740210, C allele in genotype of OXT_rs2740210, G allele in genotype of OXT_rs4813627) with an environmental burden or other risk factors would predispose the mothers to develop postpartum depression. We found no significant association between the interaction effect of the oxytocin receptor gene OXTR_rs237885 genotype depending on the occurrence of maternal postpartum depression. These findings prove the implication of the oxytocinergic system gene variants in vulnerability for postpartum depression and indicate the need for future studies adopting a multilevel approach in order to increase understanding.

Is oxytocin related to psychiatric symptoms in adolescents with obesity?

We aimed to investigate the relation of oxytocin receptor (OXTR) gene variants (rs53576 and rs2254298) and serum oxytocin (OXT) levels with psychiatric symptoms in healthy adolescents and adolescents with obesity. A total of 250 adolescents with obesity and 250 healthy adolescents were included in this study. Attachment properties, anxiety, and depression were evaluated with self-reports while diagnoses were ascertained with KIDDIE-SADS-PL Turkish version. Serum OXT level was studied with the ELISA method, and OXTR gene variants were studied by quantitative polymerase chain reaction (rs53576) and restriction fragment length polymorphism (RFLP) (rs2254298) methods. Serum OXT level was significantly lower in adolescents with obesity than in healthy controls. Self-reported symptoms of anxiety and depression were significantly elevated, especially in female adolescents with obesity, whereas parent/peer attachment was significantly lower. The rs53576 G/G genotype was found to be significantly more prevalent among obese youth. About 29.2 % of obese youth were diagnosed with psychopathology, especially anxiety and depression. OXT levels and receptor polymorphisms were not related to self-reported symptoms, attachment, and presence of psychopathology. Further studies should evaluate the roles of other constructs (e.g., early adversity, parenting, social supports, coping, temperament, etc.) and discern the roles of parent-child synchrony in elucidating relationships between OXT, pediatric obesity, and psychopathology.

THE INTERPLAY OF CHILDHOOD TRAUMA, OXYTOCIN, AND IMPULSIVITY IN PREDICTING THE ONSET OF METHAMPHETAMINE USE

Abstract Background Childhood trauma is associated with substance use disorders, including methamphetamine use disorder (MUD). Oxytocin, involved in social bonding, stress regulation, and reward processing, may influence addiction vulnerability and impulsivity in individuals with a history of childhood trauma. Aims & Objective To investigate the relationships among childhood trauma, oxytocin levels, impulsivity, and the age of first methamphetamine use in individuals with MUD. Method The study included 298 male participants (148 individuals with MUD and 150 healthy controls) from both probation offices and psychiatric clinics. Childhood trauma was assessed using the Childhood Trauma Questionnaire-Short Form (CTQ-SF), impulsivity with the Barratt Impulsiveness Scale-11 (BIS-11), and plasma oxytocin levels were obtained. Results Individuals with MUD exhibited higher levels of childhood trauma, impulsivity, and lower plasma oxytocin levels compared to healthy controls. Childhood trauma was associated with a younger age of first methamphetamine use, higher impulsivity, and lower oxytocin levels among individuals with MUD. Plasma oxytocin levels partially mediated the relationship between childhood trauma and both the age of first methamphetamine use and impulsivity. Serial mediation analysis demonstrated that oxytocin levels and impulsivity sequentially mediated the relationship between childhood trauma and the age of first methamphetamine use. Discussion & Conclusions Findings indicate that lower oxytocin levels, consequent to early adversity, can lead to increased impulsivity and earlier initiation of methamphetamine use. Previous evidence indicates that oxytocin plays a crucial role in modulating stress response, emotion regulation, and social functioning, which could be affected by early life adversity on a more fundamental level, such as influencing neurocircuitry or methylation levels of the oxytocin receptor gene. These results emphasize oxytocin's influence on reward neurocircuitry and suggest that improving oxytocin levels could potentially ameliorate methamphetamine use-related risks, contributing to more effective prevention strategies for MUD. Future research should explore oxytocin and impulsivity-focused interventions to mitigate the effects of childhood trauma and reduce MUD development risk.

Associations between genetic variations in oxytocin pathway genes and hippocampal volume: Insights from the UK Biobank.

Associations between genetic variations in oxytocin pathway genes and hippocampal volume: Insights from the UK Biobank.

Epigenetic modulation of social cognition: exploring the impact of methylation in brain-derived neurotrophic factor and oxytocin receptor genes across sex

Social cognition, which ranges from recognizing social cues to intricate inferential reasoning, is influenced by environmental factors and epigenetic mechanisms. Notably, methylation variations in stress-related genes like brain-derived neurotrophic factor (BDNF) and the oxytocin receptor (OXTR) are linked to distinct social cognitive functions and exhibit sex-specific differences. This study investigates how these methylation differences affect social cognition across sexes, focusing on both perceptual and inferential cognitive levels. Social cognitive abilities were assessed using the Korean version of the Reading the Mind in the Eyes Test (K-RMET) and Brune’s story-based Theory of Mind tasks (ToM-PST). DNA methylation levels in BDNF and OXTR were analyzed for correlations with performance on these cognitive tasks in a cohort of male and female participants. A moderation model was applied to determine if sex moderates the relationship between social cognition and DNA methylation. No significant overall correlation was found between social cognition and DNA methylation across participants. However, sex-specific correlations were identified, including a negative impact of BDNF methylation on K-RMET scores in males, and a similar effect of OXTR methylation on ToM-PST scores in females. The findings underscore the complex relationship between epigenetic modifications and social cognition, revealing sex-specific effects and highlighting the importance of considering sex in epigenetic studies of social cognition. This research contributes to understanding how epigenetic factors, influenced by sex, shape social cognitive processes and supports the need for sex-specific therapeutic approaches.

Oxytocin receptor gene single nucleotide polymorphisms in patients with bipolar disorder

Introduction Many studies have reported that psychiatric disorders may be associated with oxytocin receptor (OXTR) gene polymorphisms. The aim of this study was to investigate whether there is a relationship between OXTR gene polymorphisms and bipolar disorder (BPD). Methods The study included 100 patients diagnosed with BPD type 1 (BPD I) and 96 healthy controls. Single nucleotide polymorphisms (SNPs) of the OXTR gene, including rs53576, rs2254298 and rs2268494, were examined via polymerase chain reaction in blood samples taken from the study participants. Based on the BPD determinants, the patients were divided into 4 subgroups, as those with psychotic features, seasonal patterns, rapid cycling and peripartum onset. Results The frequency of the rs2268494 A allele was lower in the patients than in the healthy controls (p = .048), that frequency of psychotic mania was higher in patients with the rs53576 GG genotype compared to the A allele carriers (p = .003), and that of the seasonal pattern was higher in those carrying the rs2268494 A allele compared to those carrying the rs2268494 TT genotype (p < .001). Conclusion OXTR gene polymorphisms may be associated with several clinical determinants of BPD. Multicentre studies involving more subjects are required to verify these findings.

Influence of Oxytocin Level and Oxytocin Receptor Gene Expression on the Status and Severity of Autism Spectrum Disorder in a Group of Egyptian Children

Influence of Oxytocin Level and Oxytocin Receptor Gene Expression on the Status and Severity of Autism Spectrum Disorder in a Group of Egyptian Children

Influence of oxytocin level and oxytocin receptor gene expression on the status and severity of autism spectrum disorder in a group of Egyptian children

Background The use of oxytocin (OXT) as a biomarker of autism spectrum disorder (ASD) and its role in the pathophysiology of ASD is still controversial and not straightforward. Objective To evaluate, the association of ASD risk with OXT concentration and the expression of its receptor (OXTR) mRNA in a group of children with autism, in addition, to investigating the influence of OXT and OXTR on the status and severity of the disorder in the study ASD group. Patients and methods This study included 30 children diagnosed with ASD, representing the cases group, and a comparable 30 neurotypical children with matched age and sex as a control group. After detailed history taking, pedigree construction, and clinical examination to exclude recognizable syndromes, OXT level and OXTR gene expression were assessed in all included children. Results and conclusion The OXT level in autistic cases was significantly lower than in controls (P=0.0001). Also, the fold change of OXTR was significantly lower than controls (P=0.01). Receiver operating characteristic curve analysis showed that at a cut-off point of less than 0.2806, OXTR showed reasonable diagnostic performance with sensitivity, specificity, positive predictive value, and negative predictive value of 53.33, 78.2, 72.7, and 63.2, respectively (P=0.0067). At a cut-off point of less than or equal to 119 pg/ml, the OXT level showed good diagnostic performance with sensitivity (86.67%), specificity (76.67%), positive predictive value (78.8%), and negative predictive value (85.2%) (P&lt;0.0001). Our results proved the potential role of OXT plasma measurements and gene expression in diagnosing ASD at optimal cut-off values. These results support the use of OXT as a biomarker for ASD and also as a possible therapeutic option to improve the social behavior of ASD children.

Salivary oxytocin and amygdalar alterations in functional neurological disorders.

Individuals diagnosed with functional neurological disorder experience abnormal movement, gait, sensory processing or functional seizures, for which research into the pathophysiology identified psychosocial contributing factors as well as promising biomarkers. Recent pilot studies suggested that (epi-)genetic variants may act as vulnerability factors, for example, on the oxytocin pathway. This study set out to explore endogenous oxytocin hormone levels in saliva in a cohort of 59 functional neurological disorder patients and 65 healthy controls comparable in sex and age. First, we examined the association between salivary oxytocin levels with the genetic allelic variant (rs53576) of the oxytocin receptor gene (OXTR), its epigenetic changes indicated by methylation rates, and clinical variables-including childhood trauma. Second, due to previously reported effects of oxytocin changing the volume and functional connectivity of the amygdala, as well as the known involvement of the amygdala in the pathophysiology of functional neurological disorders, we further looked at both structural and functional imaging of the amygdala. While patients did not significantly differ from healthy control in their peripheral oxytocin levels, there was a specific interaction of OXTR methylation and peripheral oxytocin dependent on group: higher methylation rates correlated with higher salivary oxytocin in patients only, while this was not the case in healthy control [F(1109) = 8.92, P = 0.003, d = 0.541]. Moreover, patients with the AA-genotype (minor allele) of the rs53576 genetic variant of the OXTR gene presented with higher OXTR methylation levels [F(2106) = 10.25, P < 0.0001, d = 0.58]. Lastly, amygdalar connectivity to the hippocampus, the posterior cingulate cortex, the inferior parietal cortex and the inferior temporal cortex as well as smaller amygdalar volume were correlated to peripheral oxytocin levels in patients only [F(2,38) = 5.36, P = 0.025, d = 0.431], but not in healthy control. No significant interactions with childhood trauma were identified. Our study revealed a significant interplay between peripheral oxytocin and OXTR methylation in patients only, potentially influenced by genotype. One could hypothesize that higher peripheral oxytocin denotes a compensatory mechanisms for the increased methylation of the OXTR, which might affect amygdalar functional connectivity. These findings help to further understand underlying pathophysiological mechanisms, considering oxytocin's involvement in functional patients and could offer a potential site of treatment for future studies.

The impact of the early environment on oxytocin receptor epigenetics and potential therapeutic implications.

Oxytocin research is rapidly evolving and increasingly reveals that epigenetic modifications to the oxytocin receptor gene (OXTR) are functional, plastic, and reliable components of oxytocinergic system function. This review outlines how OXTR epigenetics are shaped by the early life environment, impact social-developmental outcomes, and have strong potential to serve as therapeutic targets. We first establish the malleability of OXTR epigenetics in infancy in both animal models and humans through research demonstrating the impact of the early life environment on OXTR DNA methylation (OXTRm) and subsequent social behavior. Next, we detail how OXTRm serves as a predictive mechanism for neurodevelopmental outcomes in animal models of social behavior such as the prairie vole, and summarize the role of OXTRm in psychiatric disorders, emotional processing, and attachment behavior in humans. We discuss the potential of further OXTRm research to improve oxytocin therapeutics by highlighting how a deeper knowledge of OXTRm could improve the therapeutic potential of exogenous oxytocin, how OXTRm may impact additional cellular mechanisms with therapeutic potential including control of the perinatal GABA switch, and how early life therapies may target the tuning of endogenous OXTRm. Finally, we review limitations of previous oxytocin research and make recommendations for future research. IMPACT: Previous research into oxytocin therapeutics has been hampered by methodological difficulties that may be improved by assay of the oxytocin receptor gene (OXTR) and its methylation (OXTRm) Key sites of OXTRm modification link early life exposures to developmental and behavioral outcomes OXTRm appears to have a critical period of development in early life Epigenetic modification of the oxytocin receptor gene could serve as a powerful target for therapeutic interventions.

Environmental and Genetic Contributions to Attachment in Late Adolescence and Young Adulthood.

Adverse childhood experiences (ACEs) have been linked with attachment insecurity and psychopathology. However, some individuals remain securely attached and resilient following ACEs. Researchers have examined polymorphisms in the oxytocin receptor gene (OXTR), particularly rs53576, as a source of resilience, though examination of the biological mechanism by which rs53576 buffers the relation that would otherwise exist between ACEs and attachment insecurity is absent. The aim of the current study was to examine how ACEs interact with individual genetic and immune vulnerability to shape attachment security in older adolescents and young adults (n = 201). Moderated mediational models were tested in which ACEs acted as independent variables, attachment security acted as a dependent variable, inflammation (i.e., IL-6) was tested as a mediator, and rs53576 (i.e., AA, AG, GG genotypes) was tested as a moderator. Results indicated that physical abuse was significantly associated with decreased attachment security, with moderation by rs53576. A significant main effect of rs53576 on IL-6 was also noted. A similar pattern of results was evident across other ACEs and suggests that the effects of ACEs on attachment are buffered by the GG genotype. Association between GG and lower IL-6 suggests inflammation plays some role, though more research is needed.

R150S mutation in the human oxytocin receptor: Gain-of-function effects and implication in autism spectrum disorder

R150S mutation in the human oxytocin receptor: Gain-of-function effects and implication in autism spectrum disorder

Epistatic interactions between oxytocin- and dopamine-related genes and trust.

Trust is an essential human trait. Although research suggests that the interplay between oxytocinergic and dopaminergic systems affects trust formation, little research has focused on epistatic (i.e., gene by gene) interaction effects of oxytocin- and dopamine-related genes on trust. Using a sample of 348 adults (114 men), we aimed to investigate the associations between genetic variants in oxytocin- and dopamine-related genes and the general, neighborhood, and institutional trust with consideration of sex differences. Three-way interaction between oxytocin-related gene genotypes, dopamine-related genotypes, and sex was found for the oxytocin receptor gene (OXTR)rs1042778 and the Catechol-O-Methyltransferase gene (COMT) rs4680 genotypes (p = 0.02) and for OXTR rs2254298 and the dopamine D2 receptor gene (DRD2) rs1800497 genotypes (p = 0.01). Further sex-stratified analyses revealed that the interaction between OXTR rs1042778 and COMT rs4680 genotypes was associated with neighborhood trust among men (p = 0.0007). Also, the interaction between OXTR rs2254298 and DRD2 rs1800497 genotypes was associated with institutional trust among men (p = 0.005). Post-hoc analyses found that men with OXTR rs1042778 TG/TT and COMT rs4680 GG genotypes reported higher neighborhood trust than those with GG + AG/AA (B = 13.49, SE = 4.68, p = 0.02), TG/TT + AG/AA (B = 23.00, SE = 5.99, p = 0.001), and GG + GG (B = 18.53, SE = 5.25, p = 0.003). Similarly, men with OXTR rs2254298 AG/AA and DRD2 rs1800497 CC genotypes showed higher institutional trust than those with AG/AA + TT/TC (B = 15.67, SE = 5.30, p = 0.02). We could not find any interacting associations among women. While we note that our sample size and candidate gene approach have a potential risk of chance findings, our study provides an important foundation toward further exploration of sex-specific epistatic interaction effects of oxytocin- and dopamine-related genes on trust, indicating the importance of both systems in trust formation.

The oxytocinergic system and racial ingroup bias in empathic neural activity

The oxytocinergic system and racial ingroup bias in empathic neural activity

Study of the association between oxytocin receptor gene polymorphism, childhood adversity and negative symptoms of schizophrenia

Is known that the neurohormone oxytocin plays an important role in the pathogenesis of mental illness, and also models the relationship between stress factors, especially those acting in the early stages of development, and the development of mental disorders. Based on these data, we investigated the effects of the interaction of the environmental factor, which was considered the adversity of childhood (ND) and the oxytocin receptor (OXTR) genotypes in the polymorphic sites rs4686302 and rs7632287, on the severity of negative symptoms of schizophrenia. The study involved 592 patients with schizophrenia (headings F20. according to ICD-10). Information about the presence of ND was obtained from case histories and patient interviews. Analysis of covariance (GML) was used for statistical data processing; in post-hoc pairwise comparison, Tukey’s test was used. A significant effect of the interaction between ND and OXTR gene polymorphism rs7632287(G/A) on the severity of negative symptoms in patients with schizophrenia was revealed. In patients without ND, polymorphisms did not have a significant effect on the studied phenotype. Thus, our study showed for the first time that the rs7632287(G/A) polymorphism and ND have a mutual effect on the severity of negative symptoms of schizophrenia.

Effects of human-animal interaction on salivary and urinary oxytocin in children and dogs

Effects of human-animal interaction on salivary and urinary oxytocin in children and dogs

The interplay between borderline personality disorder and oxytocin: a systematic narrative review on possible contribution and treatment options.

Borderline personality disorder (BPD) is a complex mental health condition marked by instability in mood, relationships, self-image, and behavior. Individuals with BPD often struggle with intense emotions, impulsivity, and maintaining stable relationships. Oxytocin, known as the "love hormone" or "bonding hormone," plays a crucial role in social bonding, trust, empathy, and emotional regulation and its dysregulation may contribute to BPD difficulties. This systematic review aims to analyze existing literature, examining the intricate interplay and encouraging future research and treatment strategies. A systematic search of Literature in PubMed, Embase and Psychinfo, without any language or time restriction, was performed until March 2024 combining thesaurus and free-search indexing terms related to "borderline personality disorder" and "oxytocin", producing 310 results (77 in PubMed, 166 in Embase and 67 in Psychinfo). Ninety-four full texts were analyzed, and 70 articles were included in qualitative analysis. Oxytocin may influence attachment styles, parental behaviors, and stress responses, particularly in individuals with a history of childhood trauma. The interaction between oxytocin, genetics, early life experiences, and environmental factors contributes to the complexity of BPD. Genetic variations in the oxytocin receptor gene may influence social and emotional abilities and contribute to the development of psychopathology. Additionally, early adverse experiences, such as childhood maltreatment, can alter oxytocin functioning, impacting social cognition and emotional regulation.However, oxytocin's role in BPD treatment remains uncertain, with some studies suggesting potential benefits for specific symptoms like social threat avoidance, while others indicate adverse effects on nonverbal behavior and mentalizing. Understanding oxytocin's role in BPD offers insights into potential therapeutic interventions. While oxytocin-based treatments may hold promise for addressing specific symptoms, further research is needed.