Table 5.

Example Evidence of the Effects of Early Life Adversity on Males’ Gene x Environment Interactions & Epigenetics

Citation	Study Design	Species	N	Early Life Adversity (ELA)			Key Findings
				Type	Timing	Measure
Gene-Environment Interactions
Bennett et al., 2002	E, P	Rhesus macaques	132	Maternal separation	Up to 7 months postnatal	N/A	In males and females, adolescents with the short allele for rh5-HTTLPR who were exposed to peer-rearing (vs. mother-reared controls) showed significantly lower CSF concentrations of a serotonin metabolite (5-HIAA) and engaged in less play and more aggressive behaviors than peer-reared monkeys without the short allele
Newman et al., 2005	E, P	Rhesus monkeys	45	Maternal absence in infancy	Up to 7 months postnatal	N/A	Mother-reared adolescent males with the low-activity-associated MAOA genotype exhibited higher aggressive responses during competitive interactions and in typical social interactions
Cicchetti et al., 2014	CS	Humans	1051	Maltreatment	Birth to age 12	CPS	Maltreatment history interacted with and OXTR and FKBP5 genotypes to predict child borderline personality symptoms, but females were at greater risk when they had minor alleles and males were at greater risk when they had major alleles.
McQuaid et al., 2019	CS	Humans	475	Maltreatment	Childhood	RSR	Childhood maltreatment was associated with depressive symptoms for females regardless of IL-1β SNP genotype, while this relationship was strongest for males carrying the GG IL-1β SNP genotype
Min et al., 2017	CS	Humans	205	Maltreatment	Up to age 16 years	RSR	In young adults, RORA gene polymorphisms interacted with childhood maltreatment to predict anxiety sensitivity only in males
Zhang et al., 2016	CS	Humans	507	Physical and emotional abuse	Up to age 16 years	RSR	In adolescents, childhood physical and emotional abuse reported interacted with MAOA genotype to predict aggressive behavior among males
Epigenetics
Weaver et al., 2004	E, P	Rats	24	Cross-fostering to high- or low-maternal care	Up to day 21	N/A	Variations in maternal care resulted in changes in DNA methylation in both male and female offspring; effects persisted into adulthood and were reversed by cross-fostering
Checknita et al., 2020	CS	Humans	194	Physical or sexual abuse	Childhood	RSR	MAOA genotype interacted with child maltreatment history to predict aggressive behaviors in adult males, and the highest levels of aggression were found among males with high levels of MAOA methylation
Cicchetti et al., 2016	CS	Humans	548	Maltreatment	Up to current age (Mean 9.4 years)	CPS	Methylation of ALDH2 was higher in maltreated compared to non-maltreated males, but was lower in maltreated compared to non-maltreated females
Essex et al., 2013	L	Humans	109	Parental stress	Infancy and preschool	PR	High parental stress during early childhood was associated with differential DNA methylation at age 15, and patterning of epigenetic marks differed by child sex
Labonté et al., 2012	Postmortem	Humans	41	Abuse	Childhood	NR	Compared with non-abused controls, adult males with a history of abuse had differential methylation in promoter regions of several genes in hippocampal neurons
McGowan et al., 2009	Postmortem	Humans	36	Maltreatment	Childhood	Proxy-based interview	Hippocampal NR3C1 gene expression was decreased in maltreated individuals compared with non-maltreated controls
Roberts et al., 2018	CS	Humans	34	Maltreatment	Up to age 18	RSR	Childhood maltreatment was associated with sperm DNA methylation in 12 DNA regions, including sites on genes associated with neuronal function, fat cell regulation, and immune function

Note: SNP, Single nucleotide polymorphism

Study Design: E=Experimental, P=Prospective, L=Longitudinal, CS=Cross-sectional

ELA Measure: CPS=Child Protective Services records; NR=Not reported; PR=Parent report; RSR=Retrospective self-report