The effect of parenting on epigenetic regulation of stress-related genes in infants

Cole, Jessica (2023) The effect of parenting on epigenetic regulation of stress-related genes in infants. Masters by Research thesis (MSc), Manchester Metropolitan University.

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Abstract

Early parental care in childhood is of key importance to ensure that children develop well socially, emotionally and cognitively, with evidence indicating that caregiver inconsistency, neglect, and a lack of love may lead to mental health problems, alongside reduced happiness and unrealised overall potential. Recent evidence indicates that 12.5% of young people and children had a mental disorder, with prevalence increasing; with approximately 5 to 10% of young children have a behavioural disorder. Therefore, since parental care is key in improving their children’s behaviour, optimising care will likely lead to better outcomes for children, lowering the risk of relationship challenges, failure at school and poor physical and mental health. Experience of trauma in early years has been shown to cause dysfunction in the genes for the Oxytocin Receptor (OXTR) glucocorticoid receptor (NR3C1) and FK506 binding protein 5 (FKBP5) genes associating with dysregulation of the hypothalamus–pituitary–adrenal (HPA) axis. This is linked to anxiety and depression-related disorders. Recent therapies using video feedback interventions to provide guidance for parents of children with behavioural problems have been shown to help improve children’s mental health. The NR3C1 gene is important in regulating stress and calming measures such as grooming and stroking have been found to reduce DNA methylation of NR3C1-1F. Changes in DNA methylation at the OXTR promoter have been linked to callous unemotional traits, internalisation problems and depression. Furthermore, studies have indicated that poor maternal care in a child’s early years leads to increased methylation of OXTR expressed in adulthood. Early-life stress has also been linked to changes in DNA methylation at the FKBP5 that are further linked to depression. The aim of this paper was to investigate the effect of epigenetic regulation of the above genes OXTR, FKBP5 and NR3C1 in children as part of the Health Start Happy Start (HSHS) video feedback intervention. Two hundred and twenty five samples from an original three hundred saliva samples taken from children whose parents/carers had participated in the HSHS intervention were analysed. DNA was extracted from each of the samples and the concentration of DNA was measured using a nano-drop UV-Vis spectrophotometer. This was followed by sodium bisulfite treatment and subsequently PCR cycling for DNA amplification. Pyromark- sequencing was then employed to analyse DNA methylation in regulatory regions at each of the genes. No clear differences in methylation at OXTR, NR3C1 and FKBP5 between VIPP and control groups or correlations in methylation at any of the genes with changes in behaviour were found following the HSHS video intervention. We did however find a significant association with NR3C1 methylation and sex-specific behavioural changes, alongside a negative association between OXTR methylation and primary caregiver’s educational attainment. This suggests that parental behaviour does not affect DNA methylation outcomes, however, there is significance in the correlation between OXTR methylation and primary caregivers’ level of education, and NR3C1 methylation and sex-specific behavioural changes.