The shared mother-child epigenetic signature of neglect is related to maternal adverse events

Abstract

Studies of DNA methylation have revealed the biological mechanisms by which life adversity confers risk for later physical and mental health problems. What remains unknown is the “biologically embedding” of maternal adverse experiences resulting in maladaptive parenting and whether these epigenetic effects are transmitted to the next generation. This study focuses on neglectful mothering indexed by a severe disregard for the basic and psychological needs of the child. Using the Illumina Human Methylation EPIC BeadChip in saliva samples, we identified genes with differentially methylated regions (DMRs) in those mothers with (n = 51), versus those without (n = 87), neglectful behavior that present similar DMRs patterns in their children being neglected versus non-neglected (n = 40 vs. 75). Mothers reported the emotional intensity of adverse life events. After covariate adjustment and multiple testing corrections, we identified 69 DMRs in the mother epigenome and 42 DMRs in the child epigenome that were simultaneously above the α = 0.01 threshold. The common set of nine DMRs contained genes related to childhood adversity, neonatal and infant diabetes, child neurobehavioral development and other health problems such as obesity, hypertension, cancer, posttraumatic stress, and the Alzheimer’s disease; four of the genes were associated with maternal life adversity. Identifying a shared epigenetic signature of neglect linked to maternal life adversity is an essential step in breaking the intergenerational transmission of one of the most common forms of childhood maltreatment.

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

“…Our model based on an EWAS analysis shows that a higher epigenetic load is a biological risk factor for adequate mother-child bonding with a potential negative impact on the child. Some direct ndings evidencing a mother-child epigenetic sharing of life adversity and psychopathology-related genes in differentially methylated regions also support this transmission to the offspring in neglect contexts (33). However, other ways of transmission may also be possible, like epigenetic changes in the mother that are passed on to her developing offspring through the offspring's fetal germ cells.…”

“…DNA was extracted from the saliva samples, and its concentration was measured by spectrophotometry at the University Hospital N. S. de Candelaria (Tenerife, Spain). Library preparation and methylation sequencing were conducted at the University of Michigan Epigenomics Core in Ann Arbor (Michigan, United States) as described previously (33). Given that DNA derived from saliva shows cellular heterogeneity, the value of the epithelial cells was calculated using the estimate LC function from ewastools R-package (34,35) with the Houseman algorithm.…”

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

“…Our EWAS-based model demonstrates that a higher epigenetic load poses a biological risk for adequate mother-child bonding, potentially impacting the child negatively. Direct evidence indicating the sharing of life adversity and psychopathology-related genes in differentially methylated regions between mothers and children supports the epigenetic transmission to the offspring in neglect contexts (36). This transmission has been proposed to occur through the fetal germ cells of the offspring when mothers have been exposed to risk factors during pregnancy (58).…”

“…The process (bisul te conversion, hybridization, methylation value correction, probes and samples out of range removed) left us with 138 mothers and 771785 probes of CpGs. Complete details of the procedure can be found in a previous study (36).…”

Mother adversity and co-residence time impact mother-child similarity in genome-wide and gene-specific methylation profiles

“…The process (bisul te conversion, hybridization, methylation value correction, probes and samples out of range removed) left us with 115 mother and child pairs and 771785 probes of CpGs. Complete details of the procedure can be found in a previous study [13].…”