Table 5 Effects of early stress on genome-wide methylation in humans
Objective | Model/tissue type | Early stress/assessment age | Epigenetic and expression changes | Interpretation | References |
|---|---|---|---|---|---|
Determine the effect of childhood SES on genome-wide methylation in adulthood | Retrospective Peripheral blood DNA | High vs low childhood SES Assessed: 45 yrs. N = 40 M | 666 gene promoters ↑ and 586 promoters ↓ methylation in high vs low childhood SES The genes involved fall into extra and intracellular signalling, DNA signalling and metabolic signalling categories. | Variations in childhood SES cause changes in genome-wide methylation in adulthood with genes in extra and intra cellular signalling and metabolic functioning | [79] |
Determine the effect of early environment on genome-wide methylation levels | Retrospective Peripheral blood DNA | Institutional care vs raised by biological parents Assessed: mean 8.25 yrs. N = 28 | Differential methylation of 914 of 26,214 CpG sites from 838 gene promoters across groupsa ↑ methylation of 744 promoters in institutionalised ↓ methylation of 94 promoters in institutionalised Promoters mainly involved in control of cellular signalling and the immune response | Early environmental alterations cause changes in methylation of a number of genes important for control of cellular signalling and the immune response in childhood | [77] |
Determine the effect of childhood abuse on genome-wide DNA methylation | Retrospective Hippocampus | CA + suicide vs no CA + suicide Assessed: adulthood N = 41 M | Differentially methylated promoters in CA vs no CA were spread across the genome 248 (68.5 %) promoters ↑ methylation in CA 114 (31.5 %) promoters ↓ methylation in CA ↑ methylation associated w ↓ mRNA exp | Childhood abuse causes alteration in the methylation of gene promoters and mRNA exp in adulthood specifically genes involved in neuronal plasticity | [93] |
Retrospective Peripheral blood DNA | PTSD + CA vs PTSD + no CA Assessed: mean age CA = 39.6 yrs. No CA = 43.69 N = 61 | Differential methylation in promoters of abused vs non-abused PTSD patients ↑ methylation in transcripts of PTSD + CA group (11.78 %) vs PTSD + no CA (0.8 %) 14 transcripts differentially methylated in CA vs no CA | Childhood abuse causes alteration to the methylation of CpG sites in both promoter regions and gene body and include specifically genes involved in CNS development in the abused PTSD group | [80] | |
Determine the effect of childhood abuse in methylation status of immune system and cytokine regulation | Retrospective Peripheral blood DNA | PTSD + CA, PTSD + no CA, C + CA, C + no CA Assessed: adulthood N = 110 | ↑ global methylation in PTSD vs C ↔ methylation due to CA in PTSD or C Gene specific associations with found in BDNF, HSF1, TLR8 for PTSD and CA ↑plasma TNFα in CA vs no CA | Childhood abuse early in life can alter global and gene specific DNA methylation patterns specifically involved in immune dysregulation | [81] |