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.

Oxytocin is considered as potential treatment targeting social dysfunctions in psychoses. However, results of clinical trials are inconsistent which may be due to genetic variation in the oxytocin system involved in social information processing.

To examine the effect of the OXTR polymorphism and its interaction with childhood adversity (CA) on facial affect recognition (FAR) in psychotic patients.

Patients with schizophrenic and affective psychotic disorders (n=934) completed a task that required labeling six basic and three social emotions. The polymorphisms rs53576 and rs7632287 within the OXTR locus were genotyped and dichotomized based on prior research. For 65% of the sample, information on CA defined as parental alcoholism or psychiatric illness was collected. The polymorphisms’ role in FAR was assessed using ANCOVAs adjusted for sex, age, and diagnosis.

After Bonferroni correction, there was a significant effect of rs53576, mainly driven by the difference between genotypes in the affective patients. GG-homozygotes recognized emotions better than A-allele carriers. A nominally significant effect in the expected direction was also found for rs7632287. CA influenced FAR but did not interact with any genotype.

The results provide further evidence that OXTR impacts social cognition and behavior in diverse cohorts, including psychotic patients, with rs53576 GG-homozygotes having enhanced social competencies. However, we have failed to confirm that OXTR modulates the relations between CA and FAR in psychosis. The difference in FAR between genotypes was more pronounced in affective patients, which might be due to more severe FAR deficits in schizophrenia.

No significant relationships.

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.