TABLE 1.

Early life stress modulates epigenetic profiles in human.

Participants	Gender	Types of ELS	Measured methods	Epigenetic outcome	Phenotypic bridge	References
Healthy adults	62% F	PA, SA, EA, PN, EN	Pyrosequencing	Glucocorticoid receptor promoter DNAm in leukocyte↓	Healthy adults exposed to ELS differ in epigenetic profile to lifetime depressed patients	Tyrka et al., 2016
Healthy young adults	50% F	PA, SA, EA, PN, EN	Pyrosequencing	1F NR3C1 promoter DNAm↑	No direct association between ELS and NR3C1-1F DNAM	Alexander et al., 2018
Infants at 2 months of age	M + F	Prenatal depressive symptoms	Pyrosequencing	1F NR3C1 promoter DNAm↑ in male infants; IV BDNF promoter DNAm↓ in both gender	No association between maternal cortisol and infant DNA methylation	Braithwaite et al., 2015
Preschool children at the age of 3–5 years	61%F	PA, SA, EA, PN, EN	Pyrosequencing	1D and 1F NR3C1 promoter DNAm↑	N/A	Tyrka et al., 2015
MDD adults	62%F	Childhood maltreatment (mixed types)	Pyrosequencing	Childhood maltreatment associated with glucocorticoid receptor promoter DNAm in peripheral blood↑	Childhood maltreatment other than depression correlated with NR3C1 expression	Bustamante et al., 2016
Suicide victims	M	Childhood abuse/neglect	Sodium bisulfite mapping	1F NR3C1 promoter DNAm↑	NR3C1 expression in hippocampus↓	McGowan et al., 2009
Suicide victims	M	Severe childhood abuse	Immunoprecipitation + microarray	248 hypermethylated and 114 hypomethylated	N/A	Labonté et al., 2012
British adults	M	PA, EA, SA	Methylated DNA immunoprecipitation + pyrosequencing	311 hypermethylated and 686 hypomethylated	N/A	Suderman et al., 2014
Young adults	53% F	PA, SA, EA, PN, EN	Microarray	Stress-related genes differently methylated	Possible increased risk for psychiatric and physical disorders	Cecil et al., 2016
Healthy adults	M	Physical aggression	Pyrosequencing	SLC6A4 promoter DNAm↑	5-HT synthesis↓	Wang et al., 2012
MDD patients	81% F	Parental loss, financial hardship, physical and sexual abuse	Pyrosequencing	SLC6A4 promoter DNAm↑	Worse depressive symptoms	Kang et al., 2013
Very preterm and full-term infants at the age of 3 months	44% F	Socio-emotional stress	Pyrosequencing	SLC6A4 promoter DNAm↑ in very preterm infants	Worse negative emotion	Montirosso et al., 2016
Monozygotic twins	Same-sex within twins	Bullying victimization	Amplified site-specific and evaluated via Sequenom EpiTYPER system	SERT promoter DNAm↑	Blunted cortisol responses to stress	Ouellet-Morin et al., 2013
Healthy young adults	50% F	Maternal prenatal stress/child maltreatment	Pyrosequencing	No significant DNAm alterations associated with ELS	Lower SERT mRNA levels	Wankerl et al., 2014
African American young adults	M	PA, SA, EA, PN, EN	Pyrosequencing	IL6 promoter DNAm↓	Pro-inflammatory response to stress	Janusek et al., 2017
MDD patients	72% F	PA, SA, EA, PN, EN	Microarray	BDNF promoter DNAm↑	BDNF polymorphisms collaborated with ELS	Ferrer et al., 2019

MDD, major depression disorder; F, female; M, male; EA, emotion abuse; SA, sexual abuse; PA, physical abuse; EN, emotion neglect; PN, physical neglect; DNAm, DNA methylation; NR3C1, neuron-specific glucocorticoid receptor; SLC6A4, serotonin transporter; BDNF, brain-derived neurotrophic factor.