Abstract Childhood adversity accounts for 50-75% of the population attributable risk for alcoholism, drug abuse, depression, and suicide. Adults’ experiences of maltreatment in childhood often lead to the intergenerational transmission of abusive or neglectful parenting behaviors, dysregulation in their children’s stress response systems, and heightened risk for psychopathology in both parent and child. Emerging research suggests that genome-wide methylation and accelerated epigenetic aging are also associated with prior experiences of child maltreatment. However, no studies have assessed the extent to which epigenetic aging and methylation patterns in human mothers and their infants are involved in conveying the impact of early adversity from mother to child. This proposal seeks funding to support epigenetic assaying of banked maternal and infant saliva samples in collaboration with the epigenetics lab of PI Dr. Kerry Ressler to allow the analysis of the resultant epigenetic data in relation to maternal and infant stress regulation, maternal-infant interaction quality, and development of the infant limbic brain. We will address this agenda by leveraging data our team has collected under R01HD079484 (Multi PI’s Dr. Teicher, McLean Hospital; Dr. Lyons-Ruth, Cambridge Hospital; Drs. Bosquet Enlow and Grant, Boston Children’s Hospital) from 150 mother-infant dyads, weighted for maternal childhood maltreatment and assessed at 4 and 15 months infant age. The first aim of this proposal will evaluate whether maternal childhood maltreatment is linked to acceleration of epigenetic aging and differential genome-wide DNA methylation in both mothers and infants, The second aim will assess whether maternal and infant epigenetic status are linked to atypical maternal and infant cortisol reactivity. The third aim will assess whether caregiving quality is related to maternal epigenetic status and infant epigenetic status. The final aim will assess whether infant epigenetic status is associated with alterations in infant limbic brain regions, particularly the amygdala and hippocampus. This initiative will be led by multiple investigators with specific expertise in: (1) epigenetic programming; (2) neurobiological effects of childhood abuse (3) maternal caregiving quality; and (4) neonatal neuroimaging. Childhood adversity and disrupted parenting are the root preventable causes for a host of medical and psychiatric disorders that result in enormous public health costs. A detailed understanding of underlying mechanisms, critical time points, and mediating factors is necessary to identify early biomarkers for infant risk and to design targeted interventions to preempt the intergenerational consequences of early adversity. We expect that the current proposal will identify specific biomarkers for risk measurable in infancy, which are currently lacking. Such biomarkers will contribute to the development of early interventions to prevent the substantial burden of stress-...