Cumulative Risk of the Oxytocin Receptor Gene Interacts with Prenatal Exposure to Oxytocin-Receptor Antagonist to Predict Children’s Social Communication Development

Background: Compelling evidence for the far-reaching role of Oxytocin (OT) in social cognition and affiliative behaviors in humans set the basis for examining the association between genetic variation in the OT receptor (OXTR) gene and risk for Autism Spectrum Disorder (ASD).

Objectives: The aim of the study was to examine gene-environment interaction of the OXTR gene and prenatal exposure to OT and OXTR antagonist (OXTRA) in predicting early social-communication development.

Methods: One hundred and fifty three children (age: M = 4.31, SD = 1.07) were assigned to 4 groups based on prenatal history: children whose mothers prenatally received OXTRA and Nifedipine to delay preterm labor (n = 27); children whose mothers received Nifedipine only to delay preterm labor (n = 35); children whose mothers received OT for labor augmentation (n = 56) and a no intervention group (n = 35). Participants completed a developmental assessment of IQ, Adaptive Behavior and social communication abilities. DNA was extracted via buccal swab. A genetic risk score was calculated based on 4 OXTR SNPs (rs53576, rs237887, rs1042778, rs2254298) previously reported to be associated with ASD symptomatology.

Results: The OXTRA group exhibited more social-communication difficulties compared to all other groups. Furthermore, higher OXTR genetic risk and being a male predicted more social-communication difficulties. Pharmacological intervention and OXTR risk interaction emerged, indicating that in the OXTRA group more risk alleles were associated with more social-communication difficulties, whereas in the Nifedipine, the OT and the no intervention groups more risk alleles were not related with social-communication difficulties, as seen in Figure 1.

Conclusions: In the current study the gene by environment interaction observed was specific to ASD related impairments, rather than a general functional deficit. Our findings demonstrate how the inclusion of targeted genetic information may help identify previously unmeasured heterogeneity in treatment response, thus highlight the importance of both genetic and environmental pathways of OT in signaling early social development. Furthermore, the current findings raise the need for further research of the association between OXTR and ASD.