Previous research concerning the interplay between genetics and parenting in the development of the parent-child relationship during adolescence has been extremely scarce, predominantly adopting single-gene designs. This limited body of work has largely overlooked the distinct effects of maternal and paternal roles, as well as potential gender differences. Additionally, existing gene-by-environment (G × E) studies have mainly concentrated on adverse environmental factors and associated negative outcomes, somewhat neglecting positive environments and outcomes. The present study examined the interactions of cumulative genetic scores (CGS, dopamine receptor D2 TaqIA and oxytocin receptor gene rs53576 polymorphisms) with both positive and negative parenting on parent-adolescent cohesion and conflict. Furthermore, this study aimed to ascertain with which gene-environment model the potential G × E interactions would align. A total of 745 Chinese Han adolescents (Mage = 13.36 ± 0.96 years; 46.8% girls) from grades 7 to 9 participated in this study. Results revealed a significant effect of CGS and negative maternal parenting on mother-adolescent conflict among males, consistent with the weak differential susceptibility model. As CGS increased, the effects of negative maternal parenting on mother-son conflict were magnified. These findings have implications for the timing and focus of interventions aimed at improving parent-adolescent relationships.

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.

Substance use disorders have been associated with alterations in the oxytocinergic system, but few studies have investigated both the peptide and epigenetic mechanisms potentially implicated in the regulation of oxytocin receptor. In this study, we compared plasma oxytocin and blood DNA methylation in the OXTR gene between people with and without cocaine use disorder (CUD). We measured the oxytocin levels of 51 people with CUD during acute abstinence and of 30 healthy controls using an enzyme immunoassay. The levels of DNA methylation in four CpG sites at exon III of the OXTR gene were evaluated in a subsample using pyrosequencing. The Addiction Severity Index was used to assess clinical characteristics. We found higher oxytocin levels in men with CUD (56.5 pg/mL; 95% CI: 48.2-64.7) than in control men (33.6 pg/mL; 95% CI: 20.7-46.5), while no differences between women with and without CUD were detected. With a moderate effect size, the interaction effect between group and sex remained significant when controlling for height, weight and age data. A positive correlation in the CUD sample was found between oxytocin levels and days of psychological suffering prior to treatment enrollment. No group differences were observed regarding DNA methylation data. This suggests that CUD is associated with higher peripheral oxytocin levels in men during acute abstinence. This finding may be considered in future studies that aim at using exogenous oxytocin as a potential treatment for cocaine addiction.

BACKGROUND: 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.
METHODS: 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.
RESULTS: 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]).
CONCLUSIONS: 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 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.

Oxytocin (OXT) is a neuropeptide and hormone involved in emotional functioning and also seems to play a role in moderating the stress response. Both preclinical and clinical studies point to an increased methylation status of the Oxytocin receptor (OXTR) promoter region with concomitant deficits in social, cognitive and emotional functioning. We hypothesize that methylation levels (%) of the oxytocin receptor promoter region correlate with the severity of depression symptoms and/or with the severity of childhood trauma within this present sample of affective disorder patients.
Eight hundred forty six (846) affective disorder patients of Central European origin were recruited at the Department of Psychiatry and Psychotherapy of the Medical University Vienna, the Karl Landsteiner University for Health and Science and Zentren für seelische Gesundheit, BBRZ-Med Leopoldau. Psychiatric assessment included a semi-structured diagnostic interview (Schedules for Clinical Assessment in Neuropsychiatry), the Hamilton Depression Scale and the Childhood Trauma Questionnaire. Concomitantly DNA samples of peripheral blood cells were collected for Multiplexed and Sensitive DNA Methylation Testing.
Our data suggests a positive but not significant association between OXTR promoter Exons 1-3 methylation levels and severity of depression symptoms as well as severity of emotional neglect in affective disorder patients and no association with childhood trauma.
Our findings contribute to elucidate the role of OXTR in affective disorders, but further longitudinal studies in particular are necessary to broaden the current state of knowledge.

Gene-Environment (G × E) interaction is of increasing importance in understanding the pathophysiology of posttraumatic stress disorder (PTSD). This study investigated the interaction effect of childhood traumatic experience and epigenetic methylation of brain-derived neurotrophic factor (BDNF) and a possible moderating effect of oxytocin receptor (OXTR) gene rs53576.
Ninety-nine patients with PTSD and 81 healthy controls (HCs) were recruited. Clinical assessments, including the childhood trauma questionnaire (CTQ) and posttraumatic stress disorder Checklist (PCL) were performed. BDNF methylation and OXTR genotyping (A vs. G allele) were conducted through blood sampling. A two-way multivariate analysis and a moderated regression analysis were conducted to investigate the moderating effect of the OXTR gene on the relationship between CTQ and BDNF methylation.
As for the HC group, the interaction effect of the CTQ and OXTR genotype was significant on BDNF methylation, and the moderation model showed that CTQ and OXTR group are significant predictors of BDNF methylation. In the G-OXTR type, the high CTQ group showed a greater BDNF methylation level. As for the PTSD group, no interaction or moderation effects were found.
The present study did not control the dosage, duration of medications, and different trauma types and the assessment of childhood trauma was based on self-report.
These results suggested that childhood traumatic experience showed a significant impact on BDNF methylation, and OXTR genes have a moderating effect on this epigenetic mechanism in people who have experienced the childhood traumatic episodes.

Previous research has highlighted the roles of oxytocin in empathy and altruistic behaviors. Based on these findings, recent studies have examined the association between the oxytocin receptor gene (OXTR) and outcome-based moral judgment with sacrificial dilemmas (e.g. runaway trolley case). However, little is known about the relationships between OXTR polymorphisms and intent-based moral judgment of harms (e.g. attempted but failed harm or intentionally committed harm). This study investigated the association between the OXTR rs53576 and intent-based moral judgment in college students (N = 544) and prisoners (N = 540). Results indicated that both students and prisoners with the GG genotype of OXTR rs53576 rated attempted but failed harm as less permissible than those with the AA and AG genotypes. These findings highlight the role of the OXTR gene in intent-based moral judgment.