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Table 5 Effects of early stress on genome-wide methylation in humans

From: Epigenetic alterations following early postnatal stress: a review on novel aetiological mechanisms of common psychiatric disorders

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]
  1. ↑ increased, ↓ decreased, ↔ no change, yrs years, SES socioeconomic status, M Male, DNA deoxyribonucleic acid, mRNA messenger ribonucleic acid, exp expression, CA childhood abuse, PTSD post-traumatic stress disorder, C controls, BDNF brain-derived neurotrophic factor, HSF1 heat shock transcription factor 1, TLR8 toll-like receptor 8, TNFα tumour necrosis factor alpha, CNS central nervous system
  2. aGenes modified by rearing environment include those involved in control of the dopaminergic system (TERF2IP), serotonin biosynthesis and serotonin receptor activity (TPH, HTR1D, HTR1F), glucocorticoid and steroid biosynthesis and their receptor activity (NRIP1, PPARGC1B, UGT), genes encoding the arginine vasopressin receptor, glutamate, cadherin and cholinergic receptors, and others which are collectively responsible for neural communication, memory formation and learning and retention