Oxytocin is a neuropeptide that has been implicated in the development and expression of social behavior. Oxytocin modulates various behaviors through its association with its single known receptor, which shows remarkable variation in distribution and density across and within species. The oxytocin receptor is encoded by OXTR, which in humans contains a methylation specific regulatory region (MT2 region) within its promotor. We have shown that increases in MT2 DNA methylation lead to decreases of gene expression in the human brain and in an animal model that blood can be used as a biomarker for the brain methylation and transcription state. Previous studies from our lab and others indicate that altered levels of DNA methylation in OXTR are a risk factor for several psychiatric disorders, including autism spectrum disorder, postpartum depression, schizophrenia, major depressive disorder, anxiety disorders, anorexia nervosa, and psychopathy. Our laboratory has also shown that OXTR methylation is related to neural endophenotypes of social perception in typicals. Importantly, social perception is also commonly dysregulated in the disorders listed. The factors that regulate the expression of the oxytocin receptor, rather than oxytocin itself, may provide an improved explanation for the variability in social behavior displayed both within and between species.
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