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.

The number of children diagnosed with autism spectrum disorder (ASD) has increased substantially over the past two decades. Current research suggests that both genetic and environmental risk factors are involved in the etiology of ASD. The goal of this paper is to examine how one specific environmental factor, early social experience, may be correlated with DNA methylation (DNAm) changes in genes associated with ASD. We present an innovative model which proposes that polygenic risk and changes in DNAm due to social experience may both contribute to the symptoms of ASD. Previous research on genetic and environmental factors implicated in the etiology of ASD will be reviewed, with an emphasis on the oxytocin receptor gene, which may be epigenetically altered by early social experience, and which plays a crucial role in social and cognitive development. Identifying an environmental risk factor for ASD (e.g., social experience) that could be modified via early intervention and which results in epigenetic (DNAm) changes, could transform our understanding of this condition, facilitate earlier identification of ASD, and guide early intervention efforts.

UNASSIGNED: Childhood maltreatment (CM) is a developmental risk factor and can negatively influence later psychological functioning, health, and development in the next generation. A comprehensive understanding of the biopsychosocial underpinnings of CM transmission would allow to identify protective factors that could disrupt the intergenerational CM risk cycle. This study examined the consequences of maternal CM and the effects of psychosocial and biological resilience factors on child attachment and stress-regulatory development using a prospective trans-disciplinary approach.
UNASSIGNED: Mother-child dyads (N = 158) participated shortly after parturition (t 0), after 3 months (t 1), and 12 months later (t 2). Mothers\' CM experiences were assessed at t 0, attachment representation at t 1 and psychosocial risk and social support were assessed at t 1 and t 2. At t 2, dyads participated in the Strange Situation Procedure (SSP). Children\'s attachmen status were classified as organized vs. disorganized, including their level of disorganized behavior, and heart rate (HR) and respiratory sinus arrhythmia (RSA) were recorded as stress response measures of the autonomic nervous system. Maternal caregiving during SSP was assessed using the AMBIANCE scale. Child\'s single nucleotide polymorphisms rs2254298 within the oxytocin receptor (OXTR) and rs2740210 of the oxytocin gene (OXT) were genotyped using DNA isolated from cord blood.
UNASSIGNED: Maternal CM experiences (CM+) were significantly associated with an unresolved attachment status, higher perceived stress and more psychological symptoms. These negative effects of CM were attenuated by social support. As expected, maternal unresolved attachment and child disorganized attachment were significantly associated. Maternal caregiving did not mediate the relationship between maternal and child attachment but influenced children\'s HR and RSA response and disorganized behavior. Moreover, the rs2254298 genotype of the OXTR gene moderated the stress response of children from mothers with CM. Children carrying the rs2740210 risk allele of the OXT gene showed more disorganized behavior independent from maternal CM experiences.
UNASSIGNED: We replicated and extended existing CM and attachment models by co-examining maternal attachment, social support, and child genetic susceptibility on child attachment and cardiovascular stress regulation. The findings contribute to an extended understanding of risk and resilience factors and enable professionals to target adequate services to parents and children at risk.

Human faces capture attention, provide information about group belonging, and elicit automatic prepared responses. Early experiences with other-race faces play a critical role in acquiring face expertise, but the exact mechanism through which early experience exerts its influence is still to be elucidated. Genetic factors and a multi-ethnic context are likely involved, but their specific influences have not been explored. This study investigated how oxytocin receptor gene (OXTR) genotypes and childcare experience interacted to regulate face categorization in adults. Information about single nucleotide polymorphisms of OXTR (rs53576) and experiences with own- and other-race child caregivers was collected from 89 Singaporean adults, who completed a visual categorization task with own- versus other-race faces. Participants were grouped into A/A homozygotes and G carriers and assigned a score to account for their type of child caregiver experience. A multivariate linear regression model was used to estimate the effect of genetic group, child caregiver experience, and their interaction on categorization reaction time. A significant interaction of genetic group and child caregiver experience (t = 2.48, p = 0.015), as well as main effects of both genetic group (t = -2.17, p = 0.033) and child caregiver experience (t = -4.29, p < 0.001) emerged. Post-hoc analysis revealed that the correlation between categorization reaction time and child caregiver experience was significantly different between the two genetic groups. A significant gene x environment interaction on face categorization appears to represent an indirect pathway through which genes and experiences interact to shape mature social sensitivity to faces in human adults.

Williams Syndrome (WS) is a rare genetic multisystem disorder that occurs because of a deletion of approximately 25 genes in the 7q11.23 chromosome region. This causes dysmorphic facial appearances, multiple congenital cardiovascular defects, delayed motor skills, and abnormalities in connective tissues and the endocrine system. The patients are mostly diagnosed with mild to moderate mental retardation, however, they have a hyper sociable, socially dis-inhibited, and outgoing personality, empathetic behavior, and are highly talkative. Oxytocin (OT), a neuropeptide synthesized at the hypothalamus, plays an important role in cognition and behavior, and is thought to be affecting WS patients\' attitudes at its different amounts. Oxytocin receptor gene (OXTR), on chromosome 3p25.3, is considered regulating oxytocin receptors, via which OT exerts its effect. WS is a crucial disorder to understand gene, hormone, brain, and behavior associations in terms of sociality and neuropsychiatric conditions. Alterations to the WS gene region offer an opportunity to deepen our understandings of autism spectrum disorder, schizophrenia, anxiety, or depression. We aim to systematically present the data available of OT/OXTR regulation and expression, and the evidence for whether these mechanisms are dysregulated in WS. These results are important, as they predict strong epigenetic control over social behavior by methylation, single nucleotide polymorphisms, and other alterations. The comparison and collaboration of these studies may help to establish a better treatment or management approach for patients with WS if backed up with future research.

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.

This study examined the moderation of an oxytocin receptor (OXTR) gene in the link between childhood adversity and depressive symptoms among incarcerated males.
Questionnaires about adverse childhood experiences and depressive symptoms, as well as genomic DNA from blood were collected among 608 incarcerated males (Mage = 32.4 years, SD = 9.41, 18-74 years). Moderation analysis was applied to examine the interaction between adverse childhood experiences (including abuse, neglect, and household dysfunction) and the OXTR polymorphisms (rs2254298, rs53576) in predicting depressive symptoms.
Incarcerated males had relatively higher prevalence of childhood adversity (70.2%) and depressive symptoms (49.8%). Higher childhood adversity was associated with increased depressive symptoms, and the effect was more pronounced in the GG homozygotes of OXTR rs2254298 (b = 0.406, p < .001), as compared with the AA/AG carriers (b = 0.236, p < .001). By contrast, the OXTR rs53576 did not interact with childhood adversity in predicting depressive symptoms.
Chinese incarcerated males with the GG genotype of OXTR rs2254298 have higher vulnerability in the effect of childhood adversity on depressive symptoms.

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.

The neuropeptide oxytocin is proposed as a promising therapy for social dysfunction by modulating amygdala-mediated social-emotional behavior. Although clinical trials report some benefits of chronic treatment, it is unclear whether efficacy may be influenced by dose frequency or genotype.
In a randomized, double-blind, placebo-controlled pharmaco-functional magnetic resonance imaging trial (150 male subjects), we investigated acute and different chronic (every day or on alternate days for 5 days) intranasal oxytocin (24 international units) effects and oxytocin receptor genotype-mediated treatment sensitivity on amygdala responses to face emotions. We also investigated similar effects on resting-state functional connectivity between the amygdala and prefrontal cortex.
A single dose of oxytocin-reduced amygdala responses to all face emotions but for threatening (fear and anger) and happy faces, this effect was abolished after daily doses for 5 days but maintained by doses given every other day. The latter dose regime also enhanced associated anxious-arousal attenuation for fear faces. Oxytocin effects on reducing amygdala responses to face emotions only occurred in AA homozygotes of rs53576 and A carriers of rs2254298. The effects of oxytocin on resting-state functional connectivity were not influenced by either dose-frequency or receptor genotype.
Infrequent chronic oxytocin administration may be therapeutically most efficient and its anxiolytic neural and behavioral actions are highly genotype-dependent in males.

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.