Aggregated epigenetic profiles explain the intergenerational transmission of physical neglect with psychiatric, cognitive, and bonding effects.

Abstract BACKGROUND. Past experiences of maltreatment and life adversity have been shown to induce DNA methylation changes in adults, but less is known about their impact on mothers’ maladaptive neglectful parenting. METHODS. We performed an epigenome-wide association study (EWAS) to investigate the role of DNA methylation levels in the intergenerational association between mothers’ past experience of childhood neglect and current maternal neglect behavior. Saliva DNA methylation was determined with the Illumina Human Methylation EPIC BeadChip. We used a trajectory inference method to derive a personalized aggregated epigenetic maternal neglect score (EMNs) from 138 mothers (n=51 in the neglect group; n=87 in the control non-neglect group) having young children. Differential methylation between groups was utilized to derive the EMNs, adjusting for education level, age, experimental variables, and blood cell types in saliva samples. RESULTS. Structural equation modelling: X 2 (29) =39.590; p =0.091; RMSEA=0.052, confirmed the EMNs as a mediator between the neglectful mothers’ past experience of physical neglect and current reports of 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 and neurodegenerative and psychopathological disorders. CONCLUSIONS. EMNs is a novel index to assess the contribution of DNA methylation changes to the intergenerational transmission of neglectful parenting behavior and its negative effects. The evidence provided expands the possibilities for earlier interventions on the neglect condition to prevent and ameliorate the impact of maternal adversities on mother-child care, helping to break the cycle of maltreatment.