Table 3.

Evidence of epigenetic embedding of early life stress

Citation		Cited association	Type of study	Population		Sample size	Key metrics
Janusek et al. (2016)		Association between childhood adversity and DNA methylation of the interleukin (IL)-6 promoter	Experimental	Adults		34	Childhood Trauma Questionnaire (CTQ), household dysfunction, DNA methylation of IL-6 promoter, salivary IL-6 and cortisol, exposure to community violence, social support, anxiety, socioeconomic status (SES), health behaviors
Khulan et al. (2014)		Association between current mental state of men exposed to early-life stress (ELS) and DNA methylation	Case-control	Adult males		166	ELS in the form of separation from their parents during childhood, age at separation, length of separation, DNA methylation, current SES, education level, history of mental health disorders, glucose, insulin, IL6, TNF-α and CRP, depression
Labonte et al. (2012)		Association between childhood adversity and epigenetic alterations of genes in hippocampal neurons in suicide completers	Case-control	Adult males		41	Severe early-life abuse assessed via interviews, methylated DNA, gene expression
Levine et al. (2015)		Association between childhood stress and increased inflammatory gene expression later in life	Cross-sectional	Adults		114	Childhood trauma, gene expression levels for PTGS2, IL-1β, and IL-8, childhood SES, childhood health, adult traumas, adulthood SES
Mehta et al. (2013)		Gene expression was associated with methylation differences in peripheral blood cells and childhood abuse among individuals with posttraumatic stress disorder (PTSD)	Case-control	Adults		169	CTQ, trauma events inventory, gene expression, DNA methylation, PTSD via symptomatic scale and clinician administered scale
Perroud et al. (2011)	Childhood sexual abuse, its severity and the number of type of maltreatments positively correlated with methylation of the glucocorticoid receptor gene (NR3C1) among individuals with borderline personality disorder (BPD)		Cross-sectional	Adults	101		CTQ, NR3C1 methylation, Screening Interview for Axis II Disorders BPD part, depression
Schwaiger et al. (2016)	Stress-responsive transcripts were enriched for genes involved in cytokine activity among individuals with history of childhood adversity		Experimental	Adults	60		CTQ, Early Trauma Inventory (ETI), genome-wide mRNA expression, Structured Clinical Interview for DSM Disorders (SKID I & II), Resilience Scale (RS-25), Brief Symptom Inventory, Trier Social Stress Test
Tyrka et al. (2012)	Parental loss, childhood maltreatment, and parental care, was associated with increased methylation of NR3C1		Cross-sectional	Adults	99		Parental Bonding Index, childhood parental Loss, CTQ, methylation of NR3C1, Dex/CRH Test, plasma cortisol, Structured Clinical Interview for DSM-IV, Inventory for Depressive Symptoms, State-Trait Anxiety Inventory, Perceived Stress Scale
van der Knaap et al. (2014)	NR3C1 methylation rates were higher after exposure to stressful life events (SLEs) during childhood and after exposure to traumatic youth experiences		Prospective	Adolescents	468		Perinatal stress, SLEs and traumatic youth experiences, methylation of NR3C1
McGowan et al. (2009)	Methylation and gene expression of NR3C1 decreased in suicide victims with a history of childhood abuse compared with controls (victims of sudden, accidental death with no history of abuse)		Case-control	Adults	36		Childhood Experience of Care and Abuse Interview, NR3C1 methylation and gene expression, Structured Clinical Interview for DSM Disorders (III-R)
Klengel et al. (2013)	Decreased methylation of the glucocorticoid receptor regulator (FKBP5) was observed in individuals exposed to child abuse and carriers of a risk allele		Case-control	Adults	152		CTQ, methylation of FKBP5, genotyping, clinician-administered PTSD scale
Romens et al. (2015)	Physical maltreatment in children was associated greater methylation of NR3C1		Cross-sectional	Children (11–14 years)	56		Physical maltreatment, NR3C1 methylation, child SES, parent martial status, parent SES (employment status, educational attainment, and occupational prestige)