Uncovering aggregated epigenetic index effects on intergenerational transmission of physical neglect and its psychiatric, cognitive, and bonding impact

Abstract Life adverse events induce DNA methylation changes, but less is known about their impact on maladaptive parenting. We use a trajectory inference method to define a personalized aggregated epigenetic maternal neglect score (EMNs) from saliva DNA methylation data. We evaluate this index as a mediator between having suffered negligence as a daughter and practicing maternal neglect to their children in a cohort of 138 mothers (n = 51 in the neglect group; n = 87 in the control non-neglect group) and with their corresponding young children. Differential methylation between the two groups was used to provide the EMNs after adjusting CpGs by the level of education, age, experimental variables, and leukocytes. Later, the explanatory role of EMNs in connecting suffered negligence in childhood with their posterior maternal neglect profile was tested through structural equation modelling (SEM). The SEM model ( X 2 (29) = 39.590; p = 0.091; RMSEA = 0.052) confirmed the EMNs as a direct mediator between mothers’ reported childhood physical neglect and psychopathological symptoms, poor cognitive integrity, and observed poor mother-child emotional availability. A third of the genes annotated to the CpGs that affect EMNs are related to cognitive impairment, neurodegenerative and psychopathological disorders. These results establish our EMNs as a novel index to assess the contribution of DNA methylation changes to the intergenerational transmission of neglectful parental behavior and its associated effects. The evidence provided expands the possibilities for earlier and targeted interventions of the neglect condition to prevent and ameliorate the negative impact of maternal adversities on mother-child care, helping to break the cycle of maltreatment.