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Table 2 Selected effect modifiers

From: Biological embedding of childhood adversity: from physiological mechanisms to clinical implications

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