Table 2.

Selected effect modifiers

Modifier	Examples of findings	Further reading
Genetic variability	• Genetic polymorphisms found to moderate associations between ELA and various outcomes; Specific examples of outcomes impacted with implicated genes include:
	o Emotional and neuroendocrine stress reactivity: 5-HTTLPR	Lester et al., 2006 [86]
	o Inflammatory response to stress: 5-HTTLPR	Fredericks et al., 2010 [88]
	o Common forms of psychopathology, including depression, ADHD, and substance addiction: NR3C1, CRHR1, OXTR, 5-HTTLPR, HTR3A, DRD2, MAOA, BDNF, COMT  o Atherosclerosis risk: MAOA	Nemeroff et al., 2016 [25] Heim & Binder, 2012 [87] Zhao et al., 2013 [89]
Child sex and gender	• Complex sex differences in HPA and autonomic dysregulation after early stress observed in animals and humans	Essex et al., 2013 [19]
	• Differential effects of maternal vs. paternal stress on boys vs. girls leads some to posit ELA effect moderation by socially embedded gender roles
	• Genetic moderators of the effects of ELA may be sex and/or gender specific  o Meta-analysis found stronger effect of MAOA genotype on psychopathology in boys  o Different polymorphism on the 5-HTTLPR gene have been linked with increased risk of depression following ELA in males vs. females	Kim-Cohen et al., 2006 [90] Brummet et al., 2008 [91]
Other child characteristics	• Pre-existing health conditions, e.g., prematurity, poor physical health status, etc. alter social and physiological consequences of ELA	Doom & Gunnar, 2015 [36]
	• Child temperament, sensitivity to the environment, and emotion processing are associated with risk for psychopathology and may affect the ways in which children respond to adversity	Lester et al., 2006 [86]
Exposure characteristics	• Characteristics of the exposure, including type (e.g., sexual, physical, emotional abuse, or neglect), chronicity, and intensity, modify associations with physical and mental health outcomes	Nemeroff et al., 2016 [25]
	• Exposures occurring during early sensitive periods can have heightened impacts on specific developmental domains leading to “timing effects”	Bick & Nelson, 2016 [21]
Social context and caregiving	• Family structure and stability, birth order, caregiver stress and social support, community and societal context may modify effects of specific adversities	Doom & Gunnar, 2015 [36]
	• Presence of a dependable, supportive caregiver may “buffer” children from effects of otherwise adverse environment
Cumulative occurrence	• Dose-response relationship between number of adversities and health and social effects are observed in large epidemiological studies	Felitti et al., 1998 [1] Danese et al., 2009 [3]

ADHD attention deficit hyperactivity disorder, HLA hypothalamic-pituitary-adrenal, ELA early life adversity