Oxytocin Receptor Gene Research Articles

Association of verbal and non-verbal theory of mind abilities with non-coding variants of OXTR in youth with autism spectrum disorder and typically developing individuals: a case-control study

BackgroundThe ability to attribute mental states to others is called theory of mind (ToM) and is a substantial component of social cognition. This ability is abnormally developed in individuals with autism spectrum disorder (ASD). Several studies over the past decade have identified the oxytocin receptor gene (OXTR) and its variants as promising components for explaining the molecular mechanisms underlying Theory of Mind (ToM). The main aim of this study is to examine the association between rs2268498 and rs53576, two functional single nucleotide polymorphisms (SNPs), and verbal and non-verbal ToM in children and adolescents with ASD and a group of typically developing youth.MethodsThe study involved 44 children and adolescents with high-functioning ASD aged 8 to 18 years old and 44 TD individuals who were matched on age and sex. In all participants, blood samples were collected and rs2268498 and rs53576 were genotyped. Happe’s Strange Stories test and the moving shapes paradigm were used to measure verbal and non-verbal ToM in all participants.ResultsThe results of permutation tests and logistic regression suggested that in TD group, rs2268498 AA carriers showed significant higher scores in variables representing verbal ToM (ToM stories and appropriateness score) whereas, in ASD group, rs53576 AA carriers exhibited significant better performance in parameters related to non-verbal ToM (ToM general rule and intentionality score). The results of hierarchical clustering in both groups support the findings by distinguishing between language-related and language-independent aspects of ToM.ConclusionsIn the present study, we examined the association between rs2268498 and rs53576 and social functioning in individuals with ASD and TD group. We found preliminary evidence that rs2268498 and rs53576 are associated with ToM related abilities in healthy individuals as well as in autistic individuals. Accordingly, rs2268498 and rs53576 may play an important role in predicting ToM capabilities. It will be necessary to conduct further research to address the association of genetic variants with a deficit in ToM in individuals with ASD.

OXTR polymorphisms associated with severity and treatment responses of schizophrenia

The mechanisms generating specific symptoms of schizophrenia remain unclear and genetic research makes it possible to explore these issues at a fundamental level. Taking into account the associations between the oxytocin system and social functions, which are apparently impaired in schizophrenia patients, we hypothesized that the oxytocin receptor gene (OXTR) might be associated with schizophrenia symptoms in both severity and responses to antipsychotics and did this exploratory positional study. A total of 2363 patients with schizophrenia (1181 males and 1182 females) included in our study were randomly allocated to seven antipsychotic treatment groups and received antipsychotic monotherapy for 6 weeks. Their blood DNA was genotyped for OXTR polymorphisms. Their symptom severity was assessed by Positive and Negative Syndrome Scale (PANSS), and the scores were transformed into seven factors (positive, disorganized, negative symptoms apathy/avolition, negative symptoms deficit of expression, hostility, anxiety and depression). Percentage changes in PANSS scores from baseline to week 6 were calculated to quantify antipsychotic responses. We found that OXTR polymorphisms were nominally associated with the severity of overall symptoms (rs237899, β = 1.669, p = 0.019), hostility symptoms (rs237899, β = 0.427, p = 0.044) and anxiety symptoms (rs13316193, β = −0.197, p = 0.038). As for treatment responses, OXTR polymorphisms were nominally associated with the improvement in negative symptoms apathy/avolition (rs2268490, β = 2.235, p = 0.0499). No association between severity or response to treatment and OXTR polymorphisms was found with statistical correction for multiplicity. Overall, our results highlighted the possibility of nominally significant associations of the OXTR gene with the severity and improvement in schizophrenia symptoms. Given the exploratory nature of this study, these associations are indicative of the role of the OXTR gene in the pathology of schizophrenia and may contribute to further elucidate the mechanism of specific symptoms of schizophrenia and to exploit antipsychotics more effective to specific symptoms.

Methylation of the Oxytocin, Oxytocin Receptor, and Vasopressin Gene Promoters in Tobacco Use Disorder during Cessation

Introduction: Vasopressin (AVP) and oxytocin (OT) exert sex-specific effects on social pair bonding and stress reactions while also influencing craving in substance use disorders. In this regard, intranasal oxytocin (OT) and AVP antagonists present potential treatments for tobacco use disorder (TUD). Since transcription of both hormones is also regulated by gene methylation, we hypothesized sex-specific changes in methylation levels of the AVP, OT, and OT receptor (OXTR) gene during nicotine withdrawal. Methods: The study population consisted of 49 smokers (29 males, 20 females) and 51 healthy non-smokers (25 males, 26 females). Blood was drawn at day 1, day 7, and day 14 of smoking cessation. Craving was assessed with the questionnaire on smoking urges (QSU). Results: Throughout cessation, mean methylation of the OT promoter gene increased in males and decreased in females. OXTR receptor methylation decreased in females, while in males it was significantly lower at day 7. Regarding the AVP promoter, mean methylation increased in males while there were no changes in females. Using mixed linear modeling, CpG position, time point, sex, and the interaction of time point and sex as well as time point, sex, and QSU had a significant fixed effect on OT and AVP gene methylation. The interaction effect suggests that sex, time point, and QSU are interrelated, meaning that, depending on the sex, methylation could be different at different time points and vice versa. There was no significant effect of QSU on mean OXTR methylation. Discussion: We identified differences at specific CpGs between controls and smokers in OT and AVP and in overall methylation of the AVP gene. Furthermore, we found sex-specific changes in mean methylation levels of the mentioned genes throughout smoking cessation, underlining the relevance of sex in the OT and vasopressin system. This is the first study on epigenetic regulation of the OT promoter in TUD. Our results have implications for research on the utility of the AVP and OT system for treating substance craving. Future studies on both targets need to analyze their effect in the context of sex, social factors, and gene regulation.

The Multifaceted Role of Oxytocinergic System and OXTR Gene.

The article explores the multifaceted role of the neuropeptide oxytocin in human behavior and its connection to the oxytocin receptor ( OXTR ) gene. Oxytocin, produced in specific brain nuclei, is implicated in emotional, social, and maternal behaviors, stress reduction, uterine contraction during childbirth, and lactation. The OXTR gene, located on chromosome 3, encodes oxytocin receptors found in various body parts, including critical brain regions associated with social behaviors. The article delves into studies on rodents, revealing correlations between OXTR gene expression and pair bonding in the prefrontal cortex and social behavior regulation in the amygdala. The discussion extends to the impact of oxytocin on social support-seeking behavior, focusing on a specific genetic variation, rs53576. The article explores how this genetic variation influences empathy, stress reactivity, and susceptibility to disorders such as autism and social anxiety. Furthermore, the article examines structural and functional changes in the brain associated with OXTR gene variations. It discusses the role of DNA methylation in influencing oxytocin receptor availability, affecting social perception and responsiveness to negative stimuli. The article also highlights the oxytocinergic system's involvement in disorders such as autism and social anxiety, emphasizing the interplay between genetics and environmental factors. The article also touches on the potential therapeutic use of exogenous oxytocin in mitigating symptoms associated with these disorders. In summary, the article underscores the intricate relationship between oxytocin, the OXTR gene, and diverse aspects of human behavior, providing insights into social bonding, perception, and the development of behavioral disorders.

Standardized mixture of Pluchea indica and Sauropus androgynus extract stimulates the gene expression associated with lactogenesis in rats

Pluchea indica (P. indica) and Sauropus androgynus (S. androgynus) are medicinal plants empirically used as an herbal galactogogue, but their mechanism of action has not been elucidated at the molecular level in the form of a mixed extract. This research aimed to standardize and investigate the combined effects of P. indica leaf extract (EPI) and S. androgynus leaf extract (ESA) on the expressions of prolactin (PRL), PRL receptor (PRLR), oxytocin (OXT), and OXT receptor (OXTR) genes in pituitary and mammary glands of lactating rats. The extracts were prepared by maceration in 70% ethanol. Standardization was done by examining non-specific parameters and determining total flavonoids using spectrophotometric analysis. Twenty-four lactating rats were divided into six groups. Group I: CMC 0.5% as control, II: EPI 500 mg/kgBW, III: ESA 125 mg/kgBW, and IV–VI were given combination formula EPI-ESA 1: 125+31.25, EPI-ESA 2: 250+62.5, and EPI-ESA 3: 500+125 mg/kgBW (orally, once a day) from the 2nd–15th day after parturition. On the 16th day, experimental animals were euthanized for tissue sampling, and gene expression was measured using real-time reverse transcription-quantitative polymerase chain reaction (RT-qPCR). The study of the non-specific parameters revealed water content, total ash, and acid-insoluble ash met criteria based on the Indonesian Herbal Pharmacopoeia. Evaluation of total flavonoids yielded 7.33% ± 0.00% and 3.84% ± 0.01% w/w for EPI and ESA, respectively. Test results showed balanced induction of all target genes was achieved when subjects received EPI-ESA 2. We concluded that EPI-ESA can potentially support lactogenesis by stimulating the expressions of PRL, PRLR, OXT, and OXTR genes.

The Effect of Peer Relationships on Adolescent Loneliness: The Role of Psychological Resilience and the OXTR Gene.

Based on the gene-environment interaction paradigm, this study explored the effect of peer relationships on adolescent loneliness and the role of psychological resilience and the oxytocin receptor gene (OXTR). A survey was conducted in a sample of 619 adolescents, and their oral cells were collected for DNA extraction and genotyping. The results showed that (1) both peer relationships and psychological resilience significantly affected adolescent loneliness; (2) psychological resilience partially mediated the relationship between peer relationships and loneliness in adolescents; (3) OXTR gene rs53576 polymorphism moderated both the first and second half of the indirect pathway of the mediation model. Specifically, carriers of the rs53576 polymorphism A/A genotype showed a significantly enhanced effect of peer relationships on adolescent psychological resilience, while carriers of the rs53576 polymorphism G/G genotype showed a significantly enhanced effect of psychological resilience on adolescent loneliness. These findings helped elucidate the developmental mechanisms of adolescent loneliness in terms of peer relationships, psychological resilience, and OXTR gene polymorphisms.

A targeted long-read sequencing approach questions the association of OXTR methylation with high-functioning autism

BackgroundDNA sequence variation and altered epigenetic regulation of the oxytocin receptor gene (OXTR) have been implicated in autism and autistic-like behaviors. While previous studies have examined subsegments of OXTR, nanopore Cas9-targeted sequencing (nCATS) allows deep characterization of entire genes with simultaneous assessment of epigenetic 5-methylcytosine (5mC) modification and without the need for prior DNA amplification or bisulfite conversion. This pilot study uses an nCATS approach to sequence the entire OXTR gene and its regulatory construct and screen for 5mC modification to compare results between individuals with high-functioning autism (HFA) and neurotypical controls (NC).MethodsUsing DNA extracted from peripheral blood, OXTR (Hg38, chr3: 8750381–8770434, 20,054 base pairs) was analyzed by nCATS. 5mC modification probabilities were calculated and visualized across the gene and differential methylation analysis was performed.ResultsTwenty adults with HFA (10 males, 10 females) and 20 age- and sex-matched NC (± 5 years) were included. There were no apparent group differences in the entire OXTR gene sequence, except for the intron variant rs918316, which was clustered in the HFA group. However, differential methylation analysis did not reveal a single significant group-dependent differentially methylated site among the 412 CpG sites captured.LimitationsLimitations of this study include the small number of samples due to the pilot nature of the study, which particularly limits the relevance of the sequence variants found. It should also be noted that the use of peripheral blood material limits the ability to draw conclusions about central processes.ConclusionsPrevious findings of autism-associated OXTR epigenetic alterations were not reproducible with our method. In our opinion, this may lead to a reconsideration of the relevance of altered methylation at individual OXTR CpG positions in autism research. However, given the pilot nature of the study, these results need to be replicated in independent cohorts and with larger sample sizes.

Parental Psychological Control, the Parent-Adolescent Relationship, and Non-suicidal Self-Injury Among Chinese Adolescents: The Moderating Effect of the Oxytocin Receptor Gene rs53576 Polymorphism.

Parental psychological control (PPC) is associated with adolescent non-suicidal self-injury (NSSI); however, its underlying mechanisms have not been extensively investigated. Considering that genetic and environmental factors interactively influence adolescent development, this study examined whether the parent-adolescent relationship mediated the link between PPC and adolescent NSSI, and whether this mediating process was moderated by the oxytocin receptor gene rs53576 polymorphism (OXTR rs53576). Participants comprised 673 adolescents (Meanage = 12.81 years, SD = 0.48 years) who completed questionnaires regarding PPC, the parent-adolescent relationship, and NSSI. DNA was extracted from each participant's saliva samples. The results indicated that the positive association between PPC and adolescent NSSI was mediated by the parent-adolescent relationship. Moreover, this indirect link was stronger for adolescents with AA homozygotes of OXTR rs53576 than for those with the GG or AG genotype. These findings extend our understanding of the association between PPC and adolescent NSSI and suggest that a simultaneous focus on PPC, the parent-adolescent relationship, and OXTR rs53576 may favor NSSI interventions.

Blood oxytocin levels and the rs4686302 polymorphism of the oxytocin receptor gene in patients with adenomyosis

BACKGROUND: An in-depth study of the pathogenesis of adenomyosis and the development of new therapeutic approaches are extremely relevant. Atosiban, a competitive oxytocin receptor antagonist, may be a promising drug with a potential therapeutic effect. Oxytocin is involved in the pathogenesis of adenomyosis-associated dysmenorrhea, and there is evidence of increased expression of the oxytocin receptor (OXTR) in the myometrium in adenomyosis and the association of the OXTR gene polymorphic variant rs4686302 with oxytocin-induced myometrial contractility.
 AIM: The aim of this study was to evaluate blood oxytocin levels and the frequency of the polymorphic variants of the oxytocin receptor gene (OXTR) rs4686302 polymorphism in patients with adenomyosis and in healthy women of reproductive age.
 MATERIALS AND METHODS: The levels of oxytocin in the blood plasma were measured by competitive enzyme immunoassay (ELISA) in patients with adenomyosis (n = 56, with mean age of 37.5 ± 8.54 years), and in women without gynecological diseases (control group; n = 33, with mean age of 32.1 ± 5.40 years). The polymorphic variant rs4686302 of the OXTR gene was analyzed by PCR-RFLP analysis in patients with adenomyosis (n = 79, with mean age of 39.9 ± 7.74 years) and in control group patients (n = 49, with mean age of 37.0 ± 9.20 years). The chi-square (χ2) test was used to analyze the distribution of genotypes and alleles. Statistical data processing was performed using the Jamovi Software, Version 1.2.27 for Windows.
 RESULTS: In patients with adenomyosis, the level of oxytocin in the blood serum was significantly higher than in control group patients: 130.0 ± 27.9 pg/ml and 95.9 ± 26.7 pg/ml, respectively. The minor allele A of the OXTR gene polymorphic variant rs4686302 was significantly more common in patients with adenomyosis (28.5%) than in women in the control group (13.3%) and in the general sample (11–15% according to the 1000 Genomes Project). The odds of developing adenomyosis in patients with the presence of the A allele (the G/A and A/A genotypes) were 2.44 times higher compared to patients with the G/G genotype (OR 2.44, 95% CI 1.13–5.28).
 CONCLUSIONS: The data obtained suggest the participation of oxytocin and its receptor in the pathogenesis of adenomyosis and requires further research in this direction.

Mild internet use is associated with epigenetic alterations of key neurotransmission genes in salivary DNA of young university students

The potentially problematic use of the Internet is a growing concern worldwide, which causes and consequences are not completely understood yet. The neurobiology of Internet addiction (IA) has attracted much attention in scientific research, which is now focusing on identifying measurable biological markers. Aim of this study was to investigate epigenetic and genetic regulation of oxytocin receptor (OXTR), dopamine transporter (DAT1) and serotonin transporter (SERT) genes using DNA obtained from saliva samples of young university students: the Internet Addiction Test (IAT) was administered to evaluate the potential existence and intensity of IA. Significant changes in DNA methylation levels at OXTR, DAT1 and SERT genes were observed in the 30 < IAT < 49 group (mild-risk internet users) compared to the IAT < 29 subjects (complete control of internet use) and IAT > 50 subjects (considered as moderately addicted). Moreover, epigenetic markers were significantly correlated, either directly (for OXTR and DAT1) or inversely (OXTR and DAT1 versus SERT), to the psychometric properties. Our data confirmed the association of OXTR, DAT1 and SERT genes in processes related to behavioural addictions and might be of relevance to suggest possible biological predictors of altered behaviours and the eventual vulnerability to develop an IA. Different other genetic pathways have been suggested to play a role in IA and research is ongoing to better define them, in order to help in the early diagnosis as well as in the development of new potential treatments.

DNA methylation of the oxytocin receptor interacts with age to impact neural response to social stimuli.

Social isolation is one of the strongest predictors of increased risk of mortality in older adulthood. The ability to form and maintain the social relationships that mitigate this risk is partially regulated by the oxytocinergic system and one's ability to attend to and process social information. We have previously shown that an epigenetic change to the DNA of the oxytocin receptor gene (OXTR methylation) affects the salience of social information in young adults. Little is known about how the oxytocinergic system ages and what effect this aging system has on social cognitive abilities throughout the lifespan. Here we explored age-related differences in the association between neural response during selective social attention and OXTR DNA methylation in young (age 18-31) and older (age 58-81) adults. Participants underwent fMRI during a selective social attention task and provided a DNA sample for the assessment of OXTR methylation. We found that older adults activated diffuse areas of visual cortex and dorsolateral prefrontal cortex during selective social attention, consistent with the dedifferentiation and compensatory neural activation commonly reported in aging. We found a significant age-by-OXTR methylation interaction on neural response when attending to social stimuli in a complex display; young adults displayed a positive association between OXTR methylation and neural activation, replicating our prior finding that young adults with presumed diminished endogenous access to oxytocin recruit regions of the attentional cortex to a greater extent. This association did not hold for older adults. Instead, perceived social support interacted with OXTR methylation to influence neural response during selective social attention. These data suggest that environmental factors like social support moderate biological processes in aging and highlight the importance of a lifespan perspective for understanding associations between individual differences in the oxytocinergic system, neural function, and social behavior.

A diet enriched with Pistacia atlantica fruits improves the female rats' reproductive system

Background and aimBaneh (Pistacia atlantica) is a plant species that is commonly consumed as food and has a long-standing traditional use as a sexual enhancer. Despite its widespread use, a limited amount of academic and scientific literature is available regarding its potential impact on the reproductive system. The present research aimed to study the effect of a diet enriched with Baneh on the female rats’ reproductive system. Experimental procedureThree groups of rats (n = 8) were subjected to the intended diet for six weeks. Subsequently, their histomorphometric parameters, sex hormone levels, as well as the expression of oxytocin (OXT) and oxytocin receptor (OXTR) genes were measured. The rats’ serum vitamin D, zinc, and lipid profiles were also evaluated. Results and conclusionResults revealed that compared to the normal food, the diet containing 20 % Baneh significantly increased the progesterone and estradiol levels three and two times, respectively. It decreased the total body weight while increasing the ratio of ovary weight to the body weight. Furthermore, the Baneh-enriched diet raised HDL, zinc, and vitamin D levels, though it reduced the LDL and TG levels by 15 μg/dl and 24 μg/dl, respectively, and the concentration of ovary malondialdehyde decreased by 50 % in the treated group. Also, the diet increased the follicle graph, corpus luteum, the thickness of the epithelium, the number of endometrial glands, and the expression of both OXT and OXTR genes. Our findings suggested that P. atlantica could considerably improve the female sex hormone levels and their reproductive system.

Relationship Between Genetic Variant Of OXTR (Rs53576) And MTNR1B (Rs1387153) And Symptoms Of Psychological Stress In Females With Gestational Diabetes Mellitus.

To assess the association of oxytocin receptor (rs53576) and melatonin hormone receptor 1B (rs1387153) gene single nucleotide polymorphisms with psychological symptoms in women with gestational diabetes mellitus. The case-control study was conducted from May 1 to June 1, 2022, at the Department of Physiology, University of Karachi, in collaboration with the Department of Biological and Biomedical Sciences, Aga Khan University, Karachi, and the Department of Obstetrics and Gynaecology, Jinnah Postgraduate Medical Centre, Karachi. Fifty gestational diabetic pregnant women and ninety healthy pregnant women were recruited. Sanger sequencing was performed to assess the genotypic frequency and polymorphic variation of all subjects. Perceived stress scale and diabetes-related distress scale were used to assess the stress levels. Data was analysed using SPSS 23. Of the 140 subjects, 90 (64.3%) were controls with mean age 24.96±4.35 years, and 50 (35.7%) were cases with mean age 28.78±5.25 (p<0.05). Mean body weight and mean gestational age were not significantly different between the groups (p>0.05). Melatonin hormone receptor 1B rs1387153 frequency was significantly different between the groups (p<0.05). Among the cases, a significant mean difference for regimen distress scores between AA and GG was observed for oxytocin receptor rs53576 (p=0.04). A significant mean difference in sum of PSS, diabetes-related stress, total diabetes- related stress and emotional distress was noted between CC and TT genotypes for melatonin hormone receptor 1B rs1387153 (p=0.001). MTNR1B rs1387153 genotypes were associated with perceived stress, diabetes-related stress, diabetic distress, and emotional burden, while OXTR rs53576 genotypes were associated with regimen distress in GDM women.

At the Head and Heart of Oxytocin’s Stress-Regulatory Neural and Cardiac Effects: A Chronic Administration RCT in Children with Autism

Introduction: Intranasal administration of oxytocin presents a promising new approach to reduce disability associated with an autism spectrum disorder diagnosis. Previous investigations have emphasized the amygdala as the neural foundation for oxytocin’s acute effects. However, to fully understand oxytocin’s therapeutic potential, it is crucial to gain insight into the neuroplastic changes in amygdala circuitry induced from chronic oxytocin administrations, particularly in pediatric populations. Objective: We aimed to examine the impact of a 4-week course of intranasal oxytocin on amygdala functional connectivity in children with autism, compared to placebo. Additionally, we investigated whether oxytocin improves cardiac autonomic arousal, as indexed by high-frequency heart rate variability. Methods: Fifty-seven children with autism aged 8–12 years (45 boys, 12 girls) participated in a double-blind, randomized pharmaco-neuroimaging trial involving twice-daily administrations of intranasal oxytocin or placebo. Resting-state fMRI scans and simultaneous, in-scanner heart rate recordings were obtained before, immediately after, and 4 weeks after the nasal spray administration period. Results: Significant reductions in intrinsic amygdala-orbitofrontal connectivity were observed, particularly at the 4-week follow-up session. These reductions were correlated with improved social symptoms and lower cardiac autonomic arousal. Further, oxytocin’s neural and cardiac autonomic effects were modulated by epigenetic modifications of the oxytocin receptor gene. The effects were more pronounced in children with reduced epigenetic methylation, signifying heightened expression of the oxytocin receptor. Conclusion: These findings underscore that a 4-week oxytocin administration course decreases amygdala connectivity and improves cardiac autonomic balance. Epigenetic modulators may explain inter-individual variation in responses to oxytocin.

Exploring linguistic markers, threat appraisals, and genetic variation during mixed‐sex couples' conflict conversations

AbstractHow couples communicate during conflict interactions can have important implications for their relational well‐being. The theory of resilience and relational load provides a valuable lens for exploring the associations among couples' language use during conflict conversations and the extent to which such conversations are perceived as threatening to one's relationship, as well as whether genetic markers moderate such associations. Forty‐seven mixed‐sex couples had a conversation about a topic causing conflict in their relationship and provided saliva samples that were tested for their genotype (GG, AA, or AG) for oxytocin receptor gene rs53576. The results revealed that neither the use of communal language nor positive emotion words were associated with perceiving the conversation as less threatening to their relationship. Genetic variation did not moderate the associations with either positive emotion word use or communal language. However, a three‐way interaction between sex, OXTR, and positive emotion word use emerged in the post hoc analyses, indicating that positive emotion word use was negatively associated with threat appraisals for women with a GG genotype, and positively associated with threat appraisals for men with a GG genotype. Implications for mixed‐sex couples' communication and research on language use during conflict conversations are discussed.

Understanding altruistic behavior: The joint role of prefrontal damage and OXTR genotype

Altruism is a type of prosocial behavior that is carried out in the absence of personal benefit or even at an expense to self. Trait altruism varies greatly across individuals, and the reasons for this variability are still not fully understood. Growing evidence suggests that altruism may be partly determined by the oxytocin receptor (OXTR) gene, which regulates the emotions underlying altruistic attitudes, such as empathy and trust. Neuroimaging and lesion studies have also implied several higher-order brain regions, including the prefrontal cortex, in altruistic behaviors. Yet the existing reports are contradictory and suggest that the top-down control exercised by the prefrontal cortex may promote both altruistic and self-interested behaviors and, thus, could obscure one's natural proclivity towards altruism encoded by OXTR.Here, we hypothesized that extensive prefrontal damage would result in an increased influence of the OXTR genotype on one's altruistic attitudes and actions. To test this hypothesis, we recruited 115 male combat veterans with penetrating traumatic brain injury to the prefrontal cortex and other brain regions, as well as 35 demographically matched control subjects without brain injury. Participants completed a self-report altruism questionnaire and were genotyped for four OXTR single nucleotide polymorphisms implicated in prosocial behavior, including rs53576, rs1042778, rs2254298 and rs7632287.Consistent with the previous studies, we found that individuals homozygotic for the G allele of rs53576 and rs7632287 were significantly more altruistic than carriers of at least one “vulnerable” A allele. Remarkably, in patients with prefrontal cortex damage, greater lesion extent was associated with significantly lower altruism scores in carriers of the A allele of rs7632287, but not in G-homozygotes, suggesting that significant disruption of the prefrontal cortex increased the influence of genetic polymorphisms on prosocial behavior. This study presents the first account of an interaction effect between the OXTR genotype and the location and extent of brain damage.

Epigenetic modification of the oxytocin receptor gene is associated with child-parent neural synchrony during competition

Interpersonal neural synchrony (INS) occurs when neural electrical activity temporally aligns between individuals during social interactions. It has been used as a metric for interpersonal closeness, often during naturalistic child-parent interactions. This study evaluated whether other biological correlates of social processing predicted the prevalence of INS during child-parent interactions, and whether their observed cooperativity modulated this association. Child-parent dyads (n = 27) performed a visuospatial tower-building task in cooperative and competitive conditions. Neural activity was recorded using mobile electroencephalogram (EEG) headsets, and experimenters coded video-recordings post-hoc for behavioral attunement. DNA methylation of the oxytocin receptor gene (OXTRm) was measured, an epigenetic modification associated with reduced oxytocin activity and socioemotional functioning. Greater INS during competition was associated with lower child OXTRm, while greater behavioral attunement during competition and cooperation was associated with higher parent OXTRm. These differential relationships suggest that interpersonal dynamics as measured by INS may be similarly reflected by other biological markers of social functioning, irrespective of observed behavior. Children’s self-perceived communication skill also showed opposite associations with parent and child OXTRm, suggesting complex relationships between children’s and their parents’ social functioning. Our findings have implications for ongoing developmental research, supporting the utility of biological metrics in characterizing interpersonal relationships.

The impact of childhood trauma exposure on social functioning in schizophrenia: the moderated mediation role of oxytocin and oxytocin receptor gene polymorphisms.

Childhood trauma has been linked to increased risk of schizophrenia and social dysfunction, and oxytocin and its receptor gene have been implicated in regulating social behavior. This study investigated the potential role of oxytocin and oxytocin receptor gene (OXTR) in mediating the effects of childhood trauma on social functioning in schizophrenia. The study consisted of 382 patients with schizophrenia and 178 healthy controls who were assessed using the Taiwanese version of the Childhood Trauma Questionnaire (CTQ-SF), the Social Functioning Scale (SFS), and plasma oxytocin levels. DNA was extracted to genotype the OXTR and ten single-nucleotide polymorphisms (SNPs; rs2254298, rs237885, rs237887, rs237899, rs53576, rs9840864, rs13316193, rs7632287, rs1042778, and rs237895) were selected. Patients with schizophrenia showed higher CTQ-SF scores (t = 12.549, p < 0.001), lower SFS scores (t = -46.951, p < 0.001), and lower plasma oxytocin levels (t = -5.448, p < 0.001) compared to healthy controls. The study also found significant differences in OXTR SNPs between both groups, with risk alleles being more prevalent in patients with schizophrenia (t = 2.734, p = 0.006). Results indicated a significant moderated mediation effect, with oxytocin and the OXTR SNPs partially mediating the relationship between childhood trauma exposure and social functioning in patients with schizophrenia (index of mediation = 0.038, 95% CI [0.033-0.044]). The findings suggest that oxytocin and its receptor gene may be promising targets for interventions aimed at improving social functioning in patients with a history of childhood trauma and schizophrenia. However, further research is needed to fully understand these effects and the potential of oxytocin-based interventions in this population.

The meaning of lithium and naltrexone pharmacotherapy in the treatment of borderline personality disorder – a narrative review

Introduction: Borderline personality disorder (BPD) affects approximately 1%-3% of the population. As the most common personality disorder, BPD features behavioural, emotional and social dysfunctions. It often co-occurs with self-harm, suicidal tendencies and substance abuse. To date, pharmacological treatment does not provide sufficient therapeutic effects. The aim of our study is to analyse the neurobiological, genetic and environmental components in the aetiopathogenesis of BPD and to collect data on the innovative use of lithium and naltrexone in the therapy of BPD. Methods: Basing on PubMed and Google Scholar databases using the following keywords: borderline, lithium, naltrexone for papers published from 1979 to 2022. Results: Difficult childhood, and emotional, sexual and physical abuse are the strongest predictors of BPD development. The core symptoms of BPD may be related to dysfunction of the serotonin, dopaminergic, endogenous system and opioid systems. Variation in 5-HTT, COMT, FKBP5 and oxytocin receptor genes may influence the course of BPD. Imaging studies have shown structural and functional abnormalities in the prefrontal cortex, amygdala and hippocampus. Lithium reduces impulsivity, aggression, suicidal tendencies and self-harm in BPD. Naltrexone may effectively reduce self-harm without suicidal tendencies, impulsivity, substance abuse and suicidality. Conclusions: No unified model has been developed to account for environmental, genetic and neurobiological components in the pathogenesis of BPD. Understanding the mechanisms is a crucial step towards personalising treatment. The use of lithium and naltrexone may have positive therapeutic effects. Randomised clinical trials are required to establish the efficacy and safety of both drugs in long-term treatment. Keywords: borderline, lithium, naltrexone

Transcriptional diversity of the oxytocin receptor in prairie voles: mechanistic implications for behavioral neuroscience and maternal physiology.

The neurohormone oxytocin regulates many aspects of physiology primarily by binding to its receptor, the oxytocin receptor. The oxytocin receptor gene (Oxtr) has been shown to have alternative transcripts in the mouse brain which may each have different biological functions or be used in specific contexts. A popular animal model for studying oxytocin-dependent social behaviors is the prairie vole, a biparental and monogamous rodent. Alternative transcriptional capacity of Oxtr in prairie voles is unknown. We used 5' rapid amplification of cDNA ends to identify alternative Oxtr transcription start sites in prairie vole brain tissue and uterine tissue. We then validated expression of specific transcripts in fetal brains and assessed the impact of exogenous oxytocin administration in utero on offspring brain development. We identified seven distinct Oxtr transcripts, all of which are present in both brain and uterine tissue. We then demonstrated that maternal oxytocin administration alters expression of a specific subset of Oxtr transcripts and that these different transcripts are under unique epigenetic regulation, such that in the perinatal period only one of the alternative transcripts is associated with DNA methylation in the Oxtr promoter. These data establish the existence of multiple Oxtr transcripts in prairie vole brain and uterine tissue and implicate oxytocin in the regulation of alternative transcript expression. These data have significant implications for our understanding of null mutant models in both mice and voles and translation in human birth and behavior.