Table 1.
Key Evidence for Propositions in The Biological Embedding of Childhood Adversity Model.
| Proposition & Evidence | Source of Evidence |
|---|---|
| 1. Disadvantage and maltreatment are chronic stressors for children. They have common features that can include unresponsive parents, harsh discipline, routine exposure to violence, and limited access to resources. | |
| -Low-SES families have limited material resources, poor living conditions, low job control, and limited coping options. |
Albelda (2001) Evans (2004) |
| -Due to these constraints, low-SES parents have less time to spend with their children and are less responsive & supportive |
Bradley et al. (2001) Dodge et al. (1994) |
| -Low-SES families tend to have more conflict, use harsher and more punitive discipline, and have inconsistent parenting. |
Leventhal & Brooks-Gunn (2000) McLoyd (1990) |
| -Children in low-SES settings are more likely to witness and experience violence, both inside and outside their homes. |
Crouch et al. (2000) Schubiner et al. (1993) |
| -Maltreatment is a “toxic” relational environment, in which children can incur physical or sexual abuse and neglect of their emotional or material needs. These different forms of maltreatment co-occur in a sizeable minority of cases. |
Arata et al. (2007) Cicchetti & Toth (2005) Dong et al. (2003) |
| 2. Chronic stress in childhood programs a pro-inflammatory phenotype in monocytes/macrophages. | |
| -Newborns exposed to maternal stress in utero have larger ex vivo inflammatory cytokine responses to microbial challenges. | Wright et al. (2010) |
| -Adults raised in low-SES families display larger ex vivo inflammatory cytokine responses to various microbial challenges. | Miller et al. (2009) |
| -Adults raised in low-SES families show reduced cortisol-mediated signaling in peripheral blood mononuclear cells, an indication of resistance to the anti-inflammatory properties of cortisol. | Miller et al. (2009) |
| -Over time, teenagers from harsh family climates display progressively larger ex vivo inflammatory cytokine responses to LPS, and greater resistance to cortisol’s anti-inflammatory effects. | Miller & Chen (2010) |
| -Adults raised in low-SES families show higher circulating levels of biomarkers like CRP and IL-6, which reflect the degree of chronic inflammation. | Danese et al. (2009), Lawlor et al. (2005), Loucks et al. (2010), Phillips et al. (2009), Pollitt et al. (2007), Schreier and Chen (2010), Tabassum et al. (2008) |
| -Adults who were maltreated in childhood show higher levels of CRP, IL-6, and other markers of chronic inflammation. | Danese et al. (2007), Kiecolt-Glaser et al. (2011), Slopen et al (2010) |
| -Adults raised in low-SES families show higher CRP, due in part to worse psychosocial functioning imparted by a harsh family of origin climate. | Taylor et al. (2006) |
| 3. Childhood stress gets embedded through epigenetic alterations to DNA, post-translational modification of proteins, and tissue remodeling. | |
| -Rats who receive low maternal care in early life show more methylation in a stretch of the glucocorticoid receptor gene promoter in the hippocampus. This change reduces expression of the gene, and by doing so increases cortisol reactivity to stress by interfering with negative feedback circuits. | Weaver et al. (2004) |
| -Cord blood cells of newborns exposed to maternal distress in utero show more methylation of a stretch of glucocorticoid receptor promoter. | Oberlander et al. (2008) |
| -Post-mortem, hippocampal slices of persons abused in youth utero show more methylation of a stretch of glucocorticoid receptor promoter. | McGowan et al. (2009) |
| -In rat pups, less nurturant parenting days 2–8 of life triggers post-translational modifications to a kinase that regulates the expression of CRH, a key trigger of HPA axis activity. | Fenoglio et al. (2006) |
| -In rat pups, less nurturant parenting days 2–8 of life results in more excitatory glutamatergic innervation of hypothalamic area centrally involved in regulating HPA axis activity. | Korosi et al. (2010) |
| -In rat pups, less nurturant parenting days 2–14 of life is associated with more extensive dendritic branching in locus coeruleus, which plays key role in regulating SNS responses to stress. | Swinny et al. (2009) |
| 4. Chronic stress in childhood gives rise to behavioral proclivities that accentuate inflammation. One route for this includes tuning of the corticolimbic circuitry, which leads to vigilance, mistrust, and subsequent difficulties with social relationships. | |
| -Children from low-SES families read more threat into situations that are ambiguous. This trait persists in adulthood. | Chen et al. (2003a, 2003b, 2004b, 2006); Miller (unpublished data) |
| -Maltreated children have selective attention for anger, perceive it more in ambiguous situations, are slower to disengage from it, and orient towards others’ conflict. | Pollak & Kistler (2002), Pollak & Sinha (2002), Pollak et al. (2005) |
| -Adults from low-SES backgrounds are more likely to endorse hostile and mistrusting beliefs about others. | Barefoot et al. (1991), Lynch et al. (1997), Scherwitz et al. (1991) |
| -Adults reared in low-SES families or maltreated as kids have smaller social networks, more conflict, and less social support. |
Graves et al. (1998) Repetti et al. (2002) |
| -Adults raised in low-SES families have larger amygdala responses when matching angry faces to neutral targets. | Gianaros et al. (2008) |
| -During emotional labeling tasks in scanner, adults from harsh families show ineffective prefrontal regulation of amygdala. | Taylor et al. (2006) |
| -Mistrust is associated with greater ex vivo pro-inflammatory cytokine production following LPS exposure, as well higher levels of the inflammatory markers CRP and IL-6. | Graham et al. (2006), Marsland et al. (2008), Suarez et al. (2002, 2004) |
| -Abrasive social encounters and poor social ties are associated with higher levels of CRP and IL-6 in circulation, activation of pro-inflammatory transcription control pathways, and reduced cortisol-mediated signaling. | Cole (2007), Fuligni et al. (2009), Loucks (2006a, 2006b), Kiecolt-Glaser et al. (2005) |
| 5. Chronic stress in childhood brings about behavioral proclivities that accentuate inflammation. Another route for this includes tuning of the corticostriatal circuitry. The resulting phenotype is impulsive, discounts the future, and has a proclivity for unhealthy behaviors. | |
| -Adults raised in low-SES families are more impulsive and tend to discount the future. | Griskevicius (2011), McLoyd (1994), Sweitzer et al. (2008) |
| -Adults from low-SES families are more likely to smoke, drink to excess, have poor diets and inactive lifestyles, and be obese. |
Lynch et al. (1997) Power et al. (2005) |
| -Impulsivity and discounting mediate a portion of the association between low SES and unhealthy lifestyles. |
Adams & White (2009) Wardle & Steptoe (2003) |
| -Adults who were maltreated in childhood more likely to smoke, be alcohol dependent, use illicit drugs, and be obese. | Felitti et al. (1998) |
| -During a monetary gain task, adults from low-SES families show reduced activity in lateral and dorsomedial prefrontal cortex, and reduced connectivity of this area with left ventral striatum. | Gianaros et al. (2010) |
| -An unhealthy lifestyle, in the form of smoking, heavy alcohol use, a poor diet, sedentary behavior, and obesity, is associated with more systemic inflammation as marked by CRP and IL-6. | Ghanim et al. (2004), Handschin (2008), Hotamisligil (2006), Kiecolt-Glaser (2010), O’Connor et al. (2009), Yanbaeva et al. (2007), Yudkin et al. (2001) |
| 6. Chronic stress in childhood alters autonomic and endocrine discharge in a durable manner, creating a hormonal milieu that accentuates inflammation. | |
| -Adults raised in low-SES families show greater diurnal output of salivary cortisol as they go about day-to-day life. | Gustafsson et al. (2009), Li et al. (2007), Miller et al. (2009) |
| -Over time, low-SES children show progressively greater output of cortisol. |
Chen, Cohen, & Miller (2010) Evans et al. (2007) |
| -Adults who were abused or neglected in childhood have altered cortisol output in daily life. In most studies cortisol levels are reduced relative to non-exposed controls, though in some cases increased output has been described. | Heim et al. (2000), Luecken et al. (2004), Lupien et al. (2009), Meewisse et al. (2007), Miller et al. (2007), Troxel & Matthews (2004), van der Vegt et al. (2009) |
| -Prolonged exposure to altered cortisol output, with low or high, can facilitate inflammatory responding of macrophages. | Raison & Miller (2003), Sapolsky et al. (2000), Sternberg (2006) |
| -Children from low-SES families have greater urinary levels of the SNS hormonal end-product, epinephrine. | Evans & English (2002) |
| -Adults raised in low-SES families show increased expression of genes switched on by SNS endproducts, epinephrine and/or norepinephrine. | Miller et al. (2009) |
| - SNS endproducts accelerate departure of pro-inflammatory myeloid progenitors into circulation. | Avitsur et al. (2005), Engler et al. (2005), Katayama et al. (2006) |
| - Norepinephrine upregulates pro-inflammatory gene expression in monocytes. Catecholamines have mixed effects on cells engaged with microbial stimuli, in some cases enhancing production of inflammatory cytokines, but in others doing the opposite. | Cole et al. (2010), Grisanti et al., (2010), Gruber-Olipitz et al. (2004), Mohamed-Ali et al. (2001), Rontgen et al., 2004, von Patay et al. (1998) |
| -Maltreatment associated with lower heart-rate variability, an index of PNS regulation of cardiac rhythms. Some evidence these links persist into adulthood. | Dale et al. (2009), Miskovic et al., (2009), Oosterman et al. (2010), Shenk et al., (2010) |
| -Cholinergic signaling inhibits macrophage production of inflammatory cytokines in mice. In humans, markers of PNS activity associates inversely with CRP and IL6 production. | Haensel et al. (2008), Marsland et al. (2007), Pavlov & Tracey (2005) |
| -Oxytocin concentrations are lower in individuals who have experienced maltreatment relative to controls. | Fries et al. (2005), Heim et al. (2009) |
| -Oxytocin attenuates magnitude of in vivo inflammatory response to LPS in humans. | Clodi et al. (2008) |
| -Oxytocin reduces inflammation and atherosclerosis in mice at risk for CHD. | Nation et al. (2010), Szeto (2008) |
| 7. Inflammation accelerates pathogenesis of chronic diseases of aging. | |
| -Inflammation contributes to development of components of the metabolic syndrome. | Hotamisligil et al. (2006) |
| -Inflammation plays a role in each stage of atherosclerosis, the condition underlying myocardial infarctions and some strokes. | Libby & Theroux (2005) |
| -Inflammation contributes to growth and spread of some tumors. | Mantovani et al. (2008) |
| -Inflammation promotes a “frailty syndrome” marked by softening of bone, loss of muscle mass, strength and function, and a decline in cognitive functions. | Chung et al. (2009) |
Note. ACTH = adrenocorticotropic hormone; CRH = corticotropin releasing hormone; CRP = C-reactive protein; HPA = hypothalamic-pituitary-adrenocortical axis; IL-6 = interleukin-6; LPS = lipopolysaccharide; PNS = parasympathetic nervous system; SES = socioeconomic status; SNS = sympathetic nervous system.