Grandmotherhood is associated with reduced OXTR DNA methylation.

In mammals, both parental and alloparental care are associated with increased brain oxytocin signaling. Grandmothers are important alloparents in many human families. Based on animal model research showing that peripheral Oxtr methylation is associated with Oxtr expression in the nucleus accumbens, we investigated whether grandmaternal caregiving is associated with lower peripheral OXTR methylation. Results reveal several regions within OXTR where grandmothers have lower DNA methylation compared with non-grandmother controls, and no regions where grandmothers have higher OXTR DNA methylation. Among grandmothers, OXTR methylation was most strongly correlated with the grandmother's assessment of the degree of positive feelings between her and the grandchild, which in turn predicted caregiving engagement. Although there was little evidence that grandmaternal OXTR methylation modulated grandmaternal neural responses to viewing photos of the grandchild within brain regions involved in caregiving motivation, it was negatively correlated with the neural response to an unknown grandchild. Thus, while OT signaling may not be essential for activating grandmaternal brain reward systems in our low-stress experimental context, it may support caregiving motivation towards unrelated children. Future longitudinal research should determine whether the transition to grandmotherhood is associated with a reduction in OXTR methylation.