The 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.
The 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.
The 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.
In 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.

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.

Oxytocin is a primary neuropeptide which coordinates affiliative behavior. Previous researchers pointed to the association between genetic vulnerability on Oxytocin Receptor Gene (OXTR) and environmental factors (e.g., social relationships) to comprehend social behavior. Although an extensive knowledge of in-person social interactions has been obtained, little is known about online sociability. A gene-environment perspective is adopted to examine how OXTR and adult attachment moderate Instagram behavior. The genetic factors within the regions OXTR/rs53576 (A/A homozygotes vs G-carriers) and OXTR/rs2254298 (G/G homozygotes vs A-carriers) were assessed. The Experience in Close Relationships-Revised (ECR-R) questionnaire was used to collect participants\' (N = 57, 16 males) attachment with a partner. The number of posts, followed people (\"followings\") and followers were obtained from Instagram, and the Social Desirability Index (SDI) was calculated as the ratio of followers to followings. Interaction effects between OXTR groups and ECR-R scores on the number of posts and SDI were hypothesized. Results showed an effect of rs53576 on the number of Instagram followings. Specifically, people with A/A OXTR/rs53576 genotype had more followings than G-carriers independent of the anxiety or avoidance felt towards their partner. These preliminary results offer insights into future investigations on social media behavior.

Background: CD38 is a transmembrane glycoprotein that regulates oxytocin (OT) production and influences social interactions. The oxytocin receptor (OXTR) has been studied intensively regarding its association with human psychosocial functions. Many studies have demonstrated a link between CD38 rs3796863 and OXTR rs53576 polymorphic regions and psychosocial characteristics as well as various psychiatric disorders in adolescents. Some studies, however, have reported null findings. Methods: The Strengths and Difficulties Questionnaire (SDQ) is a brief psychopathologic screening tool recommended for detecting psychosocial problems and psychiatric disorders in adolescents. The current field school-based study, conducted among urban Siberian adolescents (n = 298 aged 12-18), explored the SDQ scales in relation to polymorphisms of the CD38 and the OXTR genes (rs3796863 and rs53576, respectively). Results: None of the studied genotypes were associated with the SDQ results for the complete sample with presumed statistical power as 0.80 to detect a medium-size effect (Cramer\'s V = 0.3) at α = 0.0083. Post-hoc analysis in subgroups showed that OT pathway high activity may cause some negative consequences, such as emotional instability in older (aged 15-18) adolescent boys who are carriers of the rs53576 GG variant. Conclusion: Variations at the CD38 rs3796863 and OXTR rs53576 loci were not associated with psychosocial characteristics of adolescents assessed with the SDQ. In studies with a similar design, we recommend replication with larger samples and greater power to detect small effects, especially in age-sex subgroups of adolescents.

Early interactions with significant individuals affect social experience throughout the course of a lifetime, as a repeated and prolonged perception of different levels of care, independence, or control influences the modulation of emotional regulatory processes. As many factors play a role in shaping the expectations and features of social interaction, in this study, we considered the influence of parental bonding and genetic allelic variation of oxytocin receptor gene polymorphism (rs53576) over levels of experienced anxiety and avoidance in 313 young adults belonging to two different cultural contexts, namely Italy and Singapore. Results highlighted a major effect of maternal characteristics, care, and overprotection, with differences between the two cultural groups. Additionally, the interaction between rs53576 and maternal overprotection suggested different environmental susceptibility in the Italian sample and the Singaporean one. Implications for clinical work and future steps are described in the Conclusion.

Genetic variants in the oxytocin receptor (OTR) have been linked to distinct social phenotypes, psychiatric disorders and brain volume alterations in adults. However, to date, it is unknown how OTR genotype shapes prenatal brain development and whether it interacts with maternal prenatal environmental risk factors on infant brain volumes. In 105 Finnish mother-infant dyads (44 female, 11-54 days old), the association of offspring OTR genotype rs53576 and its interaction with prenatal maternal anxiety (revised Symptom Checklist 90, gestational weeks 14, 24, 34) on infant bilateral amygdalar, hippocampal and caudate volumes were probed. A sex-specific main effect of rs53576 on infant left hippocampal volumes was observed. In boys compared to girls, left hippocampal volumes were significantly larger in GG-homozygotes compared to A-allele carriers. Furthermore, genotype rs53576 and prenatal maternal anxiety significantly interacted on right hippocampal volumes irrespective of sex. Higher maternal anxiety was associated both with larger hippocampal volumes in A-allele carriers than GG-homozygotes, and, though statistically weak, also with smaller right caudate volumes in GG-homozygotes than A-allele carriers. Our study results suggest that OTR genotype enhances hippocampal neurogenesis in male GG-homozygotes. Further, prenatal maternal anxiety might induce brain alterations that render GG-homozygotes compared to A-allele carriers more vulnerable to depression.

Human beings engage in multiple social interactions daily, both in person and online. There are, however, individual differences in the frequency and quality of these interactions. This exploratory study focuses on online interactions and aims to model these differences by looking at potential environmental and genetic factors. The environmental factor is the childhood parental relationship, as reported by the participants in the dimensions of the Parental Bonding Instrument (N = 57, 41 females). At a genetic level, buccal mucosa cell samples were collected to assess participants\' genetic susceptibility, and OXTr regions rs2254298 (G/G homozygotes vs. A-carriers) and rs53576 (A/A homozygotes vs. G-carriers) were analyzed. To capture participants\' online activity, Instagram was probed. The number of people that the individual follows (\"followings\"), followers, and posts were used as a proxy for the quantity of interaction, and a Social Desirability Index (SDI) was computed as the ratio of followers to followings. An interaction between OXTr groups and parental bonding scores on the number of followings and posts was hypothesized. A gene-environment interaction for OXTr/rs2254298 on the number of Instagram posts was identified. In line with the hypothesis, participants with a genetic risk factor (A-carriers) and a history of low paternal care showed fewer Instagram posts than those without this risk factor (G/G genotype). Moreover, an interaction effect between maternal overprotection and OXTr/rs2254298 on the Instagram SDI was detected. These findings could represent an indirect pathway through which genes and parental behavior interact to shape social interactions on Instagram.

Genetic predisposition of social sensitivity might affect vulnerability to develop psychopathology after early life stress exposure. This study examined whether maternal verbally aggressive behavior in early infancy interacts with oxytocin polymorphisms in developing internalizing symptoms at ages 5-6 and 11-12. In the Amsterdam-Born-Children-and-their-Development (ABCD) study, a large observational, population-based birth cohort, maternal verbally aggressive behavior was assessed in the 13th postnatal week by a self-report questionnaire. Internalizing symptoms at age 5-6 were assessed by maternal report (N = 969) and internalizing symptoms at age 11-12 were assessed by self-report (N = 750). Data on oxytocin receptor polymorphisms rs53576 and rs2268498 and oxytocin polymorphisms rs2740210 and rs4813627 were collected. If the child was carrier of rs2740210 CA/AA polymorphism, exposure to maternal verbally aggressive behavior (10.6%) was positively associated with general anxiety at age 5-6 and emotional symptoms at age 11-12 (p for interaction = 0.011 and p = 0.015, respectively). If the child was carrier of rs4813627 GG (wild type), exposure to maternal verbally aggressive behavior was negatively associated with anxiety sensitivity and emotional symptoms at age 11-12 (p for interaction = 0.011 and p = 0.022, respectively). After exposure to maternal verbally aggressive behavior in early infancy, oxytocin polymorphisms may partly determine a child\'s vulnerability to internalizing symptoms.

The objective was to obtain developmental trajectories combining callous-unemotional traits and the number of stressful life-events between ages 3 and 9 years and to ascertain their association with the polymorphism rs53576 at the Oxytocin Receptor gene (OXTR). A total of 377 children were assessed yearly from ages 3 to 9 years. Latent class growth analysis for parallel processes was used to identify distinct trajectories for callous-unemotional traits (assessed using the Inventory of Callous-Unemotional Traits, ICU) and number of stressful life-events, and then the influence of being an A allele carrier on class membership was included with OXTR genotypes as a binary time-invariant predictor, following a 3-step approach. A 3-class model showed the highest entropy (.859) and adequate posterior probabilities of class membership (≥.884). Class 1 (n = 226, 59.9%) included children with low and stable ICU scores and low and descending stressful life-events; class 2 (n = 127, 33.7%) included children with high and ascending ICU scores and low and slightly descending stressful life-events; and class 3 (n = 24, 6.4%) included children with persistently high profiles both for ICU scores and stressful life-events. Carrying an A allele (genotypes GA/AA) increased the odds of pertaining to class 3 (high and persistent ICU scores and stressful life-events) as opposed to class 2 (OR = 4.27, p = 0.034) or class 1 (OR = 3.81, p = 0.042). The results suggest the importance of considering callous-unemotional traits and stressful life-events in conjunction. In addition, the genetic variability of OXTR (rs53576) may help to understand individual differences in early development.

Postpartum depression (PPD) is a debilitating mental illness affecting approximately 13% of mothers after birth. Both genetic and psychosocial factors contribute to PPD risk, but very little is known about how these factors interact. We tested whether the rs53576 polymorphism in the oxytocin receptor (OXTR) gene accounts for variation in the impact of low social support as a risk factor for depression among mothers during the perinatal period. New mothers (N = 220) provided saliva or blood DNA samples and completed surveys assessing PPD symptoms and perceived social support. In a significant interaction, social support from the baby\'s father predicted PPD symptoms to a greater extent among mothers with the GG compared to AG and AA genotypes. These results add to converging evidence that variation in OXTR rs53576 moderates the impact of the social environment on PPD.