CONNELLY LAB
Research
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.
Epigenetic regulation of the oxytocin receptor (OXTR) and human social cognition
We are interested in the effect DNA methylation of the oxytocin receptor (OXTR) on human cognition and neural endophenotypes. Our lab has shown that DNA methylation of OXTR effects neural processing of social stimuli such as facial emotions, ultimately affecting perception. Current projects in this area of study include extending these findings to children and infants, determining the effect of maternal interactions during infancy on OXTR methylation in adulthood, and determining the effect of OXTR methylation in adolescence on behavioral outcomes in adulthood.
Epigenetic regulation of social behaviors in prairie voles
In collaboration with Sue Carter and Karen Bales, we have recently characterized a unique model system to study the epigenetic modification of OXTR, the prairie vole (Microtus ochrogaster). In this model as in humans, early life experience plays an important role in modulating the oxytocinergic system which registers and responds to early life events like parenting and exposure to oxytocin during birth. Specifically, the conserved MT2 region changes methylation state in both the brain and the blood with differences in parental care and in response to maternal oxytocin level during labor. These changes correspond to coordinate changes in gene and protein expression early in life leading to dramatic changes in social behavior as adults. These behaviors are controlled in part by oxytocin’s action in the nucleus accumbens and include changes in alloparental care, pair bond formation, and anxiety-like behaviors.
We seek to further characterize the molecular cascade that leads to epigenetic changes at OXTR by targeted modification of the methylation state of the locus, and dissection of the upstream signals that lead to these changes. In doing so, this will lead to a better understanding of the establishment of the dysregulation of the locus early in life that may lead to susceptibility to neurological disease and provide a molecular framework from which we can manipulate this locus to modify disease state and potentially impact social behavior.
Contact Us
Thanks for your interest in our research. Get in touch with us for any questions or comments regarding our work and publications. We’d love to hear from you.
Gilmer Hall, Room 175
485 McCormick Road
Charlottesville, VA 22903
434-982-4439