A Common Oxytocin Receptor Polymorphism Interacts with Adverse Social Experiences In Influencing Brain Responses to Angry Faces and Social-Affective Problems

Background:  

Over the past several years, there has been a growing interest in the role of oxytocin (OT) in the neurobiological basis of social behaviour, and in social and affective disorders (e.g., autism spectrum disorders, anxiety disorders). While nasal OT administration has been hailed as a possible treatment for these disorders, animal work indicates that OT-effects may chiefly depend on OT-receptor expression in the brain.  More specifically, the comparison between high social-affiliative prairie voles and ‘asocial’ montane voles suggests that 1) social attachment formation requires linking social cues to OT-receptors in brain regions involved in reward processes, and that 2) in high social-affiliative species, especially females, OT-receptor expression and social behaviour are affected by adverse social experiences during development.

Objectives:

We used a gene-neuroimaging approach in 393 13-14 year-old adolescents from the IMAGEN sample to test the hypotheses that 1) rs2268494, a common OXTR-polymorphism previously linked to autism and social behaviour, influences brain activity in reward regions to social threat; 2) that OXTR-genotype effects are moderated by adverse social experiences, primarily in girls; and 3), that genotype x environment-dependent ventral striatal activity affects social and affective functioning.

Methods:

65 AA/AT and 328 TT-carriers of central European descent, matched on age, IQ, and puberty development, were assessed on fMRI BOLD reactivity to anger expressions, frequency of negative life events, and conduct, peer, and emotional problems.  

Results:  

We found that genotype effects on brain reactivity in regions implicated in reward processing and mentalising (the ability to infer others thoughts and feelings) were moderated by gender and negative experiences. In girls, only minor A-carriers but not TT-genotype showed decreased ventral striatal activity after negative experiences, which in turn increased risk for social-emotional problems. in boys, the A-allele was associated with increased reactivity in regions engaged in mentalizing and fewer emotional and behavioural problems. This supports reports of abnormal reactivity in the mentalizing network in male-dominant disorders of social dysfunction (ASD, conduct disorder).

Conclusions:  

Together, our findings point to a novel neurobehavioural mechanism through which the OXTR polymorphism rs2268494 interacts with negative experiences in contributing to risk versus resilience for social-emotional problems in adolescent boys and girls. We will discuss implications for ASD.