Research across species has shown that the neuropeptide oxytocin plays a key role in the regulation of social cognition and behavior. It is important for attachment, social exploration, and social recognition, as well as anxiety and stress-related behaviors. Based on oxytocin administration studies and measurements of peripheral oxytocin levels, it has been suggested that signaling of oxytocin is impaired in mental disorders associated with social deficits, including autism, borderline personality disorder, and social anxiety disorder. There are several factors influencing interindividual differences in social-cognitive abilities and differences in the susceptibility to psychiatric disorders, including variability in genes involved in oxytocin signaling. In addition to sequence variation, interindividual differences might in part be explained by variation in epigenetic processes influencing gene expression. Here, we provide an overview of the functional organization and epigenetic regulation of the murine and human oxytocin receptor gene.
Studies in mice have shown that the oxytocin receptor gene (Oxtr) is epigenetically regulated by DNA methylation with experience- and tissue-specific expression patterns. In humans, functional studies on epigenetic mechanisms have focused on oxytocin receptor gene (OXTR) DNA methylation and have provided evidence for the influence of OXTR promoter methylation on OXTR mRNA expression. A small number of studies have investigated the role of OXTR methylation in behavioral phenotypes and mental illness. There is first evidence that OXTR methylation is associated with different aspects of social cognition as well as with psychiatric disorders characterized by deficits in social cognition, including autism, high callous-unemotional traits in youth, social anxiety, and anorexia nervosa.
Given evidence that epigenetic states of genes can be modified by experiences, especially those occurring in sensitive periods early in development, we conclude with a discussion on the effects of traumatic experience on the developing oxytocin system. Epigenetic modification of genes involved in oxytocin signaling might play a part in the mechanisms mediating the long-term influence of early adverse experiences on socio-behavioral outcomes.
Oxytocin receptor DNA methylation Social cognition Autism Developmental programming
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