Early life stress, air pollution, inflammation, and disease: An integrative review and immunologic model of social-environmental adversity and lifespan health

“…compared to individuals experiencing none of these types of adversity, and a 4- to 12-fold increase in risk for smoking, self-rated health complaints, alcoholism, drug abuse, depression, heart disease, and suicide (Anda et al., 2008; Dong et al., 2004; Dube et al., 2009; Felitti et al., 1998).”

“Indeed, several psychiatric disorders including substance abuse, post-traumatic stress disorder, depression, and schizophrenia have been linked to both early adversity exposure and inflammation, as have many somatic conditions, such as metabolic, cardiovascular, neoplastic, and rheumatic diseases (Anda et al., 2008, 2…”

“, IL-6, TNFα)- on cellular activities (enzyme, receptor, ion channel, genomic) (Juster et al., 2010; McEwen, 1998; McEwen and Wingfield, 2003).”

“In this context, the terms early life stress or early adversity, have referred to different types of stressors, including violence, poverty, maltreatment, abuse, and neglect, as well as parental substance abuse or mental illness (Carroll et al., 2011; Dube et al., 2001; Hughes et al., 2017; Infurna et al., 2016; Lacey…”

“Second, many of these diseases have an underlying inflammatory component (Danese et al., 2009; O’Neill et al., 2007; Slavich and Irwin, 2014; Wellen and Hotamisligil, 2005).”

“In human studies, early life stress has been associated with modifications of hypothalamic–pituitary–adrenal (HPA) axis- and neuroplasticity-related methylation patterns (Labonté et al., 2012; McGowan et al., 2009; Mehta et al., 2013).”

“In this context, the terms early life stress or early adversity, have referred to different types of stressors, including violence, poverty, maltreatment, abuse, and neglect, as well as parental substance abuse or mental illness (Carroll et al., 2011; Dube et al., 2001; Hughes et al., 2017; Infurna et al., 2016; Lacey…”

“, IL-6, TNFα)- on cellular activities (enzyme, receptor, ion channel, genomic) (Juster et al., 2010; McEwen, 1998; McEwen and Wingfield, 2003).”

“Factors such as poverty and SES although unfixed, also tend to persist across life (Chetty et al., 2014).”

“Moreover, psychosocial stress and particle air pollution seem to influence the same inflammatory processes, such as inducing oxidative stress, as well as activating NF-κB and TLR4 (see Fig.”

“In this context, the terms early life stress or early adversity, have referred to different types of stressors, including violence, poverty, maltreatment, abuse, and neglect, as well as parental substance abuse or mental illness (Carroll et al., 2011; Dube et al., 2001; Hughes et al., 2017; Infurna et al., 2016; Lacey…”

“…disadvantage experience stress early in life and develop a sensitivity to air pollution characterized by a pro-inflammatory phenotype, while also being more likely to experience higher exposure to air pollution across the lifespan (Boehmer et al., 2013; Cicchetti and Toth, 2005; Evans, 2004).”

“In this context, the terms early life stress or early adversity, have referred to different types of stressors, including violence, poverty, maltreatment, abuse, and neglect, as well as parental substance abuse or mental illness (Carroll et al., 2011; Dube et al., 2001; Hughes et al., 2017; Infurna et al., 2016; Lacey…”

“Indeed, several psychiatric disorders including substance abuse, post-traumatic stress disorder, depression, and schizophrenia have been linked to both early adversity exposure and inflammation, as have many somatic conditions, such as metabolic, cardiovascular, neoplastic, and rheumatic diseases (Anda et al., 2008, 2…”

“Notably, NF-κB signaling is central to the human inflammatory machinery and can also be activated by toll-like receptor ligands of LPS (some of which can be attached to PM), hypoxic condition, and TNF-α.”

“Because exposure to stressors that trigger inflammation is socially patterned, however, these findings are also important for understanding how disparities in immunologic-related health outcomes may develop and persist over time (Miller et al., 2011).”

“5 and ozone) even at concentrations below national standards and noted that these effects appeared most potent among socially disadvantaged individuals, such as racial minorities and people with low income (Di et al., 2017).”

“Indeed, several psychiatric disorders including substance abuse, post-traumatic stress disorder, depression, and schizophrenia have been linked to both early adversity exposure and inflammation, as have many somatic conditions, such as metabolic, cardiovascular, neoplastic, and rheumatic diseases (Anda et al., 2008, 2…”

“Second, many of these diseases have an underlying inflammatory component (Danese et al., 2009; O’Neill et al., 2007; Slavich and Irwin, 2014; Wellen and Hotamisligil, 2005).”

“First, research is necessary to understand which specific types of life stress most strongly trigger inflammation and lead to the development of a proinflammatory phenotype (Epel et al., 2018; Irwin and Slavich, 2017; Slavich et al., 2010).”

“6-fold increase in physical inactivity and severe obesity compared to individuals experiencing none of these types of adversity, and a 4- to 12-fold increase in risk for smoking, self-rated health complaints, alcoholism, drug abuse, depression, heart disease, and suicide (Anda et al., 2008; Dong et al., 2004; Dube et…”

“The persistence of a phenotype into adulthood is also plausible as increased inflammatory activity can sustain and further exacerbate the impaired function of the glucocorticoid receptor (Miller et al., 2009; Pace et al., 2007; Zunszain et al., 2011).”

“Indeed, several psychiatric disorders including substance abuse, post-traumatic stress disorder, depression, and schizophrenia have been linked to both early adversity exposure and inflammation, as have many somatic conditions, such as metabolic, cardiovascular, neoplastic, and rheumatic diseases (Anda et al., 2008, 2…”

“Socially disadvantaged individuals, such as those with low educational attainment or income, or who belong to racial or ethnic groups that have historically experienced discrimination, systematically experience relatively worse health across the lifespan, compared to those in more socially advantageous circumstances (…”

“As a result, early life stress exposure is now recognized as a critical public health concern across the world (Shonkoff, 2010).”

“Notably, NF-κB signaling is central to the human inflammatory machinery and can also be activated by toll-like receptor ligands of LPS (some of which can be attached to PM), hypoxic condition, and TNF-α.”

“In this context, the terms early life stress or early adversity, have referred to different types of stressors, including violence, poverty, maltreatment, abuse, and neglect, as well as parental substance abuse or mental illness (Carroll et al., 2011; Dube et al., 2001; Hughes et al., 2017; Infurna et al., 2016; Lacey…”

“In this context, the terms early life stress or early adversity, have referred to different types of stressors, including violence, poverty, maltreatment, abuse, and neglect, as well as parental substance abuse or mental illness (Carroll et al., 2011; Dube et al., 2001; Hughes et al., 2017; Infurna et al., 2016; Lacey…”

“Shankardass et al. (2009) studied 2497 children aged 5–9 years old from the Children’s Health Study (McConnell et al., 2006; Shankardass et al., 2009), and looked at doctor-diagnosed new onset of asthma during a 3-year follow-up.”

“The persistence of a phenotype into adulthood is also plausible as increased inflammatory activity can sustain and further exacerbate the impaired function of the glucocorticoid receptor (Miller et al., 2009; Pace et al., 2007; Zunszain et al., 2011).”

“However, although studies rarely account for exposure to both poor air quality and social disadvantage, the health impact of chronic exposure to poor air quality is closely intertwined with the negative health effects of social stressors that are also more concentrated among those who are socially disadvantaged, such…”

“Notably, NF-κB signaling is central to the human inflammatory machinery and can also be activated by toll-like receptor ligands of LPS (some of which can be attached to PM), hypoxic condition, and TNF-α.”

“…an experience of psychosocial stress involving social evaluation and threat, are particularly interesting as they provide experimental evidence that social stress plays a causal role in activating inflammatory processes (Carpenter et al., 2007, 2010, 2009; Elzinga et al., 2008; Gouin et al., 2012).”

“Inflammation is central to the biological machinery that links air pollution with adverse health outcomes (Du et al., 2016; Mostafavi et al., 2015).”

“Subsequently, IL-1β and TNF-α regulate the expression of various secondary cytokines and chemokines, including IL-6 and IL-8.”

“The persistence of a phenotype into adulthood is also plausible as increased inflammatory activity can sustain and further exacerbate the impaired function of the glucocorticoid receptor (Miller et al., 2009; Pace et al., 2007; Zunszain et al., 2011).”

“In one study that sampled caregivers of brain-cancer patients, for example, exposure to chronic stress was associated with increased expression of transcripts with response elements for NF-κB and reduced expression of transcripts bearing response elements for glucocorticoids (Miller et al., 2008).”

“In human studies, early life stress has been associated with modifications of hypothalamic–pituitary–adrenal (HPA) axis- and neuroplasticity-related methylation patterns (Labonté et al., 2012; McGowan et al., 2009; Mehta et al., 2013).”

“For example, inhaled traffic-related PM enters the lungs and causes a local inflammatory response from alveolar macrophage and bronchial epithelial cells (Bai and Sun, 2015); it is noteworthy that this response can be indexed by the production of the same pro-inflammatory cytokines that are triggered by life stress (G…”

“Indeed, genes involved in inflammation are well-known to influence the effects that life stress has on health (for a review, see Slavich and Cole, 2013).”

“Given that the inflammatory response to particle air pollution is mediated by the activation of NF-κB via oxidative stress, a psychosocially induced increase in expression of NF-κB could potentiate the inflammatory response to air pollution (Fiordelisi et al., 2017).”

“Increased methylation of the glucocorticoid receptor gene reduces its function and disturbs the feedback of the HPA axis, while binding of FKBP5 protein inhibits the glucocorticoid receptor (Tyrka et al., 2012).”

“Notably, NF-κB signaling is central to the human inflammatory machinery and can also be activated by toll-like receptor ligands of LPS (some of which can be attached to PM), hypoxic condition, and TNF-α.”

“5), has also been associated with increased risk of adverse birth outcomes, respiratory disease, diabetes, and atherosclerosis, as well as poor neurodevelopment and cognitive function (Table 4) (Bobak, 2000; Bowatte et al., 2017; Calderón-Garcidueñas et al., 2015; Campen et al., 2012; Esposito et al., 2016; Malmqvist…”

“In this context, the terms early life stress or early adversity, have referred to different types of stressors, including violence, poverty, maltreatment, abuse, and neglect, as well as parental substance abuse or mental illness (Carroll et al., 2011; Dube et al., 2001; Hughes et al., 2017; Infurna et al., 2016; Lacey…”

“For example, inhaled traffic-related PM enters the lungs and causes a local inflammatory response from alveolar macrophage and bronchial epithelial cells (Bai and Sun, 2015); it is noteworthy that this response can be indexed by the production of the same pro-inflammatory cytokines that are triggered by life stress (G…”

“These include disorders that cause substantial disease burden worldwide, including cardiovascular disease, autoimmune diseases, lung cancer, and depression (Bernatsky et al., 2016; Brunekreef and Holgate, 2002; Calderón-Garcidueñas et al., 2015; Lim et al., 2012).”

“6-fold increase in physical inactivity and severe obesity compared to individuals experiencing none of these types of adversity, and a 4- to 12-fold increase in risk for smoking, self-rated health complaints, alcoholism, drug abuse, depression, heart disease, and suicide (Anda et al., 2008; Dong et al., 2004; Dube et…”

“Moreover, studies have shown that many of these stressors are more common among socially disadvantaged populations, suggesting that these exposures may contribute to structuring social disparities in health (Slopen et al., 2016).”

“Indeed, early adversity has been linked with increased risk for a wide variety of mental and physical health problems in addition to those identified above, including asthma, rheumatoid arthritis, cardiovascular disease, type 2 diabetes, certain types of cancer, and accelerated cognitive decline (Brown et al., 2010; D…”

“Findings from simulated laboratory-based social stressors, such as the Trier Social Stress Test that induces an experience of psychosocial stress involving social evaluation and threat, are particularly interesting as they provide experimental evidence that social stress plays a causal role in activating inflammatory…”

“First, research is necessary to understand which specific types of life stress most strongly trigger inflammation and lead to the development of a proinflammatory phenotype (Epel et al., 2018; Irwin and Slavich, 2017; Slavich et al., 2010).”

“…Dong et al., 2004, 2003; Dube et al., 2009; Felitti et al., 1998; Halonen et al., 2015; Kivimaki et al., 2006; Korkeila et al., 2010; Mantovani et al., 2008; Miller et al., 2011; Nanni et al., 2012; Packard et al., 2011; Scrivo et al., 2011; Slavich and Irwin, 2014; Wolitzky-Taylor et al., 2017).”

“Notably, NF-κB signaling is central to the human inflammatory machinery and can also be activated by toll-like receptor ligands of LPS (some of which can be attached to PM), hypoxic condition, and TNF-α.”

“A harmful exposure common among socially disadvantaged populations is psychosocial stress during childhood (Andersen and Blosnich, 2013; Slopen et al., 2016).”

“In this context, the terms early life stress or early adversity, have referred to different types of stressors, including violence, poverty, maltreatment, abuse, and neglect, as well as parental substance abuse or mental illness (Carroll et al., 2011; Dube et al., 2001; Hughes et al., 2017; Infurna et al., 2016; Lacey…”

“The notion that early life stress can affect health has been around for centuries (Monroe and Slavich, 2016; Slavich, 2016).”

“In this context, the terms early life stress or early adversity, have referred to different types of stressors, including violence, poverty, maltreatment, abuse, and neglect, as well as parental substance abuse or mental illness (Carroll et al., 2011; Dube et al., 2001; Hughes et al., 2017; Infurna et al., 2016; Lacey…”

“Researchers have also found associations between experiences of bullying in childhood (9–16 years) and elevated CRP levels in young adulthood (19–21 years) (Copeland et al., 2014), as well as exposure to victimization during childhood (birth-12 years) and elevated levels of CRP at age 18 years (Baldwin et al.”

“…expression of glucocorticoid receptor-β can lead to cellular insensitivity to glucocorticoids, including in airway cells, creating a physiologic environment that favors the production of proinflammatory cytokines and increases systemic inflammation (Cain and Cidlowski, 2015; Hamid et al., 1999).”

“Toxicology research in humans and animal models shows that exposure to particle air pollution can result in both local and systemic inflammation (Table 4) (Ogino et al., 2017; Ostro et al., 2014; Riva et al., 2011).”

“…inhaled traffic-related PM enters the lungs and causes a local inflammatory response from alveolar macrophage and bronchial epithelial cells (Bai and Sun, 2015); it is noteworthy that this response can be indexed by the production of the same pro-inflammatory cytokines that are triggered by…”

“5), has also been associated with increased risk of adverse birth outcomes, respiratory disease, diabetes, and atherosclerosis, as well as poor neurodevelopment and cognitive function (Table 4) (Bobak, 2000; Bowatte et al., 2017; Calderón-Garcidueñas et al., 2015; Campen et al., 2012; Esposito et al., 2016; Malmqvist…”

“, 2017; Burgermeister, 2007), as well as lifetime stress exposure measurement (Shields and Slavich, 2017; Slavich, 2016; Slavich and Shields, 2018).”

“These findings are also broadly consistent with evidence showing that individuals from low socioeconomic backgrounds (which can give rise to stress) have greater air-pollution related mortality than their higher socioeconomic counterparts (Forastiere et al., 2007; Jerrett et al., 2004; Krewski et al., 2003).”

“Indeed, several psychiatric disorders including substance abuse, post-traumatic stress disorder, depression, and schizophrenia have been linked to both early adversity exposure and inflammation, as have many somatic conditions, such as metabolic, cardiovascular, neoplastic, and rheumatic diseases (Anda et al., 2008, 2…”

“Although the specific mechanisms by which early life stress becomes biologically embedded are not yet fully understood, at least one pathway likely involves early life stress-related programming of a proinflammatory phenotype via changes in the epigenetic regulation of gene expression (Table 3) (Khulan et al., 2014; L…”

“As a starting point, therefore, stress researchers are referred to a set of reviews summarizing air pollution exposure assessment methods (Krzyzanowski, 1997; Mirowsky and Gordon, 2015; Zhang and Lioy, 2002; Zou et al., 2009), as well as the USEPA’s online resources for human air pollution exposure.”

“Notably, NF-κB signaling is central to the human inflammatory machinery and can also be activated by toll-like receptor ligands of LPS (some of which can be attached to PM), hypoxic condition, and TNF-α.”

“Second, many of these diseases have an underlying inflammatory component (Danese et al., 2009; O’Neill et al., 2007; Slavich and Irwin, 2014; Wellen and Hotamisligil, 2005).”

“…(Danese and McEwen, 2012; Gouin et al., 2012; Heim et al., 2002; Heleniak et al., 2016; Hornung and Heim, 2014; Levine et al., 2015; McLaughlin, 2016; Miller and Chen, 2010; Nusslock and Miller, 2016; Schwaiger et al., 2016; Slopen et al., 2013; Steptoe et al., 2002b, 2002a; Winzeler et al., 2017).”

“Moreover, the effects of severe early life stressors that cause repeated biological stress responses or prolonged biological dysregulation, such as poverty, abuse, neglect, isolation, discrimination, humiliation, or violence, appear to be particularly deleterious for lifespan health (Goodman et al., 2005; Horwitz, 200…”

“…or mental illness (Carroll et al., 2011; Dube et al., 2001; Hughes et al., 2017; Infurna et al., 2016; Lacey et al., 2014; Lindert et al., 2014; McCrory et al., 2011; Miller and Chen, 2010; Norman et al., 2012; Pollitt et al., 2007; Sripada et al., 2014; Varese et al., 2012; Zatti et al., 2017).”

“…are also broadly consistent with evidence showing that individuals from low socioeconomic backgrounds (which can give rise to stress) have greater air-pollution related mortality than their higher socioeconomic counterparts (Forastiere et al., 2007; Jerrett et al., 2004; Krewski et al., 2003).”

“…that cause repeated biological stress responses or prolonged biological dysregulation, such as poverty, abuse, neglect, isolation, discrimination, humiliation, or violence, appear to be particularly deleterious for lifespan health (Goodman et al., 2005; Horwitz, 2002; Nurius et al., 2013).”

“…or mental illness (Carroll et al., 2011; Dube et al., 2001; Hughes et al., 2017; Infurna et al., 2016; Lacey et al., 2014; Lindert et al., 2014; McCrory et al., 2011; Miller and Chen, 2010; Norman et al., 2012; Pollitt et al., 2007; Sripada et al., 2014; Varese et al., 2012; Zatti et al., 2017).”

“Moreover, elevated levels of inflammation appear to persist into adulthood, even among disease-free adults with a history of disadvantage or maltreatment during childhood (Juonala et al., 2006).”

“…the glucocorticoid receptor gene (NR3C1; a key regulator of inflammatory activity) (McGowan et al., 2009; Romens et al., 2014; Tyrka et al., 2012; van der Knaap et al., 2014) as well as demethylation of the FKBP5 gene, which increases the expression of the FK506 protein, an important regulator…”

“(2018) conducted epigenome-wide analyses in peripheral blood from participants of the Environmental Risk (E-Risk) Longitudinal Study (Moffitt, 2002) and found no support for the hypothesis of robust changes in DNA methylation in young (18-year olds) individuals with history of victimization (Marzi et al., 2018).”

“Moreover, psychosocial stress and particle air pollution seem to influence the same inflammatory processes, such as inducing oxidative stress, as well as activating NF-κB and TLR4 (see Fig.”

“5), has also been associated with increased risk of adverse birth outcomes, respiratory disease, diabetes, and atherosclerosis, as well as poor neurodevelopment and cognitive function (Table 4) (Bobak, 2000; Bowatte et al., 2017; Calderón-Garcidueñas et al., 2015; Campen et al., 2012; Esposito et al., 2016; Malmqvist…”

“Inflammatory mechanisms linking air pollution and health Toxicology research in humans and animal models shows that exposure to particle air pollution can result in both local and systemic inflammation (Table 4) (Ogino et al., 2017; Ostro et al., 2014; Riva et al., 2011).”

“(2008) studied the interaction between chronic exposure to chronic family stress and traffic-related air pollution in predicting biologic and clinical outcomes in 73 children with asthma (Chen et al., 2008).”

“However, although studies rarely account for exposure to both poor air quality and social disadvantage, the health impact of chronic exposure to poor air quality is closely intertwined with the negative health effects of social stressors that are also more concentrated among those who are socially disadvantaged, such…”

“, 2014), as well as exposure to victimization during childhood (birth-12 years) and elevated levels of CRP at age 18 years (Baldwin et al., 2018).”

“Toll-like receptors and related scavenger receptors, such as CD36 and lectin-like oxidized LDL receptor-1 (LOX-1), are the major immune sensors that recognize pathogen-associated and damage-associated molecular patterns arising from inflammation, infection, or cell stress, and these receptors have been mechanistically…”

“The evidence discussed in previous sections also suggests that the pro-inflammatory phenotype results in increased inflammatory reactivity to inflammation-inducing factors, other than air pollution, such as psychosocial stress and pathogens (Baumeister et al., 2016; Carpenter et al., 2010, 2009, 2007; Elzinga et al.,…”

“Consistent with this possibility, initial research has demonstrated associations between early life stress and genome-wide methylation in adulthood, which was in turn related to increased production of IL-6 following an immunologic challenge (Janusek et al., 2017; Lam et al., 2012).”

“To the extent that this is true, a better understanding of how this pro-inflammatory phenotype develops, as well as what interventions might help reduce inflammation-related health risks, will be important for reducing health disparities and improving population health worldwide (Slavich, 2015).”

“Indeed, several psychiatric disorders including substance abuse, post-traumatic stress disorder, depression, and schizophrenia have been linked to both early adversity exposure and inflammation, as have many somatic conditions, such as metabolic, cardiovascular, neoplastic, and rheumatic diseases (Anda et al., 2008, 2…”

“Moreover, psychosocial stress and particle air pollution seem to influence the same inflammatory processes, such as inducing oxidative stress, as well as activating NF-κB and TLR4 (see Fig.”

“well as pro-inflammatory cytokines that drive the acute inflammatory response—namely, interleukin-1β (IL-1β), interleukin 6 (IL-6), and tumor necrosis factor alpha (TNF-α) (Fagundes and Way, 2014; Miller and Cole, 2012; Slavich and Auerbach, 2018).”

“Allostatic load as described by (McEwen and Stellar, 1993) refers to the “wear and tear” the body experiences in response to repeated allostatic activations caused by persistent perception of psychosocial stressors.”

“Similarly, a longitudinal birth-cohort study of 7462 participants recently found that social isolation during ages 7–11 predicted higher levels of CRP at 44 years of age (Lacey et al., 2014).”

“First, high levels of chronic peripheral inflammation, indexed by circulatory inflammatory markers, have been associated with experiences of early life stress in both crosssectional (Carroll et al., 2011; Dixon et al., 2009; Gouin et al., 2012; Grosse et al., 2016; Hartwell et al., 2013; Lacey et al., 2013; Lehto et a…”

“Finally, there is evidence that experiencing even one major life stressor involving social threat during adolescence can lead to greater upregulation of pro-inflammatory molecular signaling pathways (Murphy et al., 2013) and downregulation of anti-inflammatory pathways (Murphy et al.”

“First, high levels of chronic peripheral inflammation, indexed by circulatory inflammatory markers, have been associated with experiences of early life stress in both crosssectional (Carroll et al., 2011; Dixon et al., 2009; Gouin et al., 2012; Grosse et al., 2016; Hartwell et al., 2013; Lacey et al., 2013; Lehto et a…”

“Notably, NF-κB signaling is central to the human inflammatory machinery and can also be activated by toll-like receptor ligands of LPS (some of which can be attached to PM), hypoxic condition, and TNF-α.”

“Environmental health researchers, in turn, are referred to a set of reviews summarizing early life stress measures (Appleton et al., 2017; Burgermeister, 2007), as well as lifetime stress exposure measurement (Shields and Slavich, 2017; Slavich, 2016; Slavich and Shields, 2018).”

“Indeed, several psychiatric disorders including substance abuse, post-traumatic stress disorder, depression, and schizophrenia have been linked to both early adversity exposure and inflammation, as have many somatic conditions, such as metabolic, cardiovascular, neoplastic, and rheumatic diseases (Anda et al., 2008, 2…”

“As a starting point, therefore, stress researchers are referred to a set of reviews summarizing air pollution exposure assessment methods (Krzyzanowski, 1997; Mirowsky and Gordon, 2015; Zhang and Lioy, 2002; Zou et al., 2009), as well as the USEPA’s online resources for human air pollution exposure.”

“…early life stress in both crosssectional (Carroll et al., 2011; Dixon et al., 2009; Gouin et al., 2012; Grosse et al., 2016; Hartwell et al., 2013; Lacey et al., 2013; Lehto et al., 2012; Lin et al., 2016; Moreira et al., 2018; Munjiza et al., 2018; Packard et al., 2011) and longitudinal studies…”

“5), has also been associated with increased risk of adverse birth outcomes, respiratory disease, diabetes, and atherosclerosis, as well as poor neurodevelopment and cognitive function (Table 4) (Bobak, 2000; Bowatte et al., 2017; Calderón-Garcidueñas et al., 2015; Campen et al., 2012; Esposito et al., 2016; Malmqvist…”

“, FEV1 and FVC) among children of parents reporting higher perceived stress, after adjusting for household socioeconomic status (Islam et al., 2011).”

“Inflammation is central to the biological machinery that links air pollution with adverse health outcomes (Du et al., 2016; Mostafavi et al., 2015).”

“5), has also been associated with increased risk of adverse birth outcomes, respiratory disease, diabetes, and atherosclerosis, as well as poor neurodevelopment and cognitive function (Table 4) (Bobak, 2000; Bowatte et al., 2017; Calderón-Garcidueñas et al., 2015; Campen et al., 2012; Esposito et al., 2016; Malmqvist…”

“Toll-like receptors and related scavenger receptors, such as CD36 and lectin-like oxidized LDL receptor-1 (LOX-1), are the major immune sensors that recognize pathogen-associated and damage-associated molecular patterns arising from inflammation, infection, or cell stress, and these receptors have been mechanistically…”

“Environmental health researchers, in turn, are referred to a set of reviews summarizing early life stress measures (Appleton et al., 2017; Burgermeister, 2007), as well as lifetime stress exposure measurement (Shields and Slavich, 2017; Slavich, 2016; Slavich and Shields, 2018).”

“To this end, we recently proposed a broad framework that accounts for a wide range of overlapping social and environmental exposures across the lifespan and delineates underlying biobehavioral pathways that lead to chronic illness (Olvera Alvarez et al., 2018).”

“Inflammatory mechanisms linking air pollution and health Toxicology research in humans and animal models shows that exposure to particle air pollution can result in both local and systemic inflammation (Table 4) (Ogino et al., 2017; Ostro et al., 2014; Riva et al., 2011).”

“Notably, NF-κB signaling is central to the human inflammatory machinery and can also be activated by toll-like receptor ligands of LPS (some of which can be attached to PM), hypoxic condition, and TNF-α.”

“First, high levels of chronic peripheral inflammation, indexed by circulatory inflammatory markers, have been associated with experiences of early life stress in both crosssectional (Carroll et al., 2011; Dixon et al., 2009; Gouin et al., 2012; Grosse et al., 2016; Hartwell et al., 2013; Lacey et al., 2013; Lehto et a…”

“Notably, NF-κB signaling is central to the human inflammatory machinery and can also be activated by toll-like receptor ligands of LPS (some of which can be attached to PM), hypoxic condition, and TNF-α.”

“well as pro-inflammatory cytokines that drive the acute inflammatory response—namely, interleukin-1β (IL-1β), interleukin 6 (IL-6), and tumor necrosis factor alpha (TNF-α) (Fagundes and Way, 2014; Miller and Cole, 2012; Slavich and Auerbach, 2018).”

“Recent studies in health psychology and psychoneuroimmunology have focused on elucidating biological mechanisms that may explain how early life stress affects mental and physical health in later life (Shields and Slavich, 2017; Slavich, 2018).”

“…biologically embedded are not yet fully understood, at least one pathway likely involves early life stress-related programming of a proinflammatory phenotype via changes in the epigenetic regulation of gene expression (Table 3) (Khulan et al., 2014; Levine et al., 2015; Szyf and Bick, 2012)}.”

“Moreover, the effects of severe early life stressors that cause repeated biological stress responses or prolonged biological dysregulation, such as poverty, abuse, neglect, isolation, discrimination, humiliation, or violence, appear to be particularly deleterious for lifespan health (Goodman et al., 2005; Horwitz, 200…”

“In addition to these findings, lower family socioeconomic status in childhood has been associated with increased cellular inflammatory reactivity to ex vivo LPS exposure, as indexed by the cytokines IL-6 and TNF-α (Azad et al., 2012; Miller et al., 2009; Schreier et al., 2014; Wright et al., 2010).”