Developmental psychoneuroendocrine and psychoneuroimmune pathways from childhood adversity to disease
Open accessAbstract
Childhood adversity has been repeatedly and robustly linked to physical and mental illness across the lifespan. Yet, the biological pathways through which this occurs remain unclear. Functioning of the inflammatory arm of the immune system and the hypothalamic-pituitary-adrenal (HPA)-axis are both hypothesized pathways through which childhood adversity leads to disease. This review provides a novel developmental framework for examining the role of adversity type and timing in inflammatory and HPA-axis functioning. In particular, we identify elements of childhood adversity that are salient to the developing organism: physical threat, disrupted caregiving, and unpredictable environmental conditions. We propose that existing, well-characterized animal models may be useful in differentiating the effects of these adversity elements and review both the animal and human literature that supports these ideas. To support these hypotheses, we also provide a detailed description of the development and structure of both the HPA-axis and the inflammatory arm of the immune system, as well as recent methodological advances in their measurement. Recommendations for future basic, developmental, translational, and clinical research are discussed.
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Written from the paper’s full text.
TL;DR
This review proposes that childhood adversity shapes later disease risk through the HPA-axis and inflammatory immune pathways, but argues that effects depend on adversity type and developmental timing. It maps physical threat, disrupted caregiving, and unpredictability onto candidate animal models and highlights infancy and adolescence as possible sensitive periods.
Key findings
- The review argues that treating adversity as a single dose-response exposure obscures distinct biological signatures. Physical trauma/injury may be linked to exaggerated acute HPA-axis and inflammatory reactivity; disrupted caregiving may impair glucocorticoid negative feedback and promote glucocorticoid insensitivity; unpredictable environments may elevate basal/diurnal cortisol and inflammation through heightened threat vigilance.
- Proposed animal analogs are repeated social defeat (RSD; e.g., 2-hour daily defeat episodes for one week) for physical trauma, maternal separation for caregiving disruption, and chronic variable stress (CVS; varied stressors twice daily for 15–30 days) for unpredictability. RSD reportedly produces anxiety-like behavior in about two-thirds of rodents; CVS can raise hippocampal IL-6, IL-1β, and TNF-α.
- Timing is central: the HPA-axis and immune system develop from gestation through adolescence. Infancy, especially the first two years, and adolescence are highlighted as possible sensitive periods; early adversity may program pro-inflammatory tendencies, while adolescent adversity may relate to lower cortisol and elevated inflammation.
- The review notes that childhood adversity is reported to account for roughly one-third of psychiatric disorders and that C-reactive protein above 3.0 mg/L is considered predictive of cardiovascular disease risk. It calls for measures capturing adversity subtypes and timing, plus repeated multi-system assessments.
Methods
- Narrative translational review, not a primary study or meta-analysis. It synthesizes animal and human literature on HPA-axis and inflammatory correlates of childhood adversity.
- Organizes evidence by three proposed adversity elements—physical threat, disrupted caregiving, and unpredictable environment—and by developmental timing, pairing each element with a candidate rodent model (RSD, maternal separation, CVS).
- Reviews measurement approaches for HPA-axis function (salivary cortisol, area under the curve, cortisol awakening response, diurnal rhythm) and inflammation (circulating cytokines and CRP, cellular and intracellular assays), and discusses developmental physiology.
Limitations
- Stated: rodent-to-human translation is indirect; some human adversities lack animal analogs; sexual abuse is grouped with physical trauma despite likely distinct neurodevelopmental correlates; animal models omit human psychological features, such as abuse by a known caregiver versus a novel intruder; RSD and CVS are adult-animal models while maternal separation is infancy-only; the framework is narrow in developmental and physiological scope and excludes prenatal programming, direct sympathetic-health pathways, brain development, and genetic risk.
- Evident from the text: many proposed pathways remain untested; human evidence is often cross-sectional, retrospective, or uses broad adversity windows; timing effects are difficult to separate from duration and ongoing stress; measurement tools rarely capture biologically salient subtypes or precise timing; few studies measure HPA-axis and inflammation together or distinguish reactivity from recovery.
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Claims the paper makes
0 of 172 cited sources checked · 0 supported · 0 flagged
- Premisecitation
Childhood adversity is a robust risk factor for mental and physical illness.
“Childhood adversity has been repeatedly and robustly linked to physical and mental illness across the lifespan.”
- Also stated in: § 1.1 Introduction · plain
“Childhood adversity is a robust risk factor for mental and physical illness (Chapman et al., 2004; Felitti et al., 1998) as well as earlier mortality (Chen et al., 2016).”
Quote in the paperSubstantial claim0 of 2 sources checked - Also stated in: § 1.1 Introduction · plain
- Premisecitation
Healthy, typically developing humans show their highest cortisol concentrations in the morning and their lowest in the evening.
“Healthy, typically-developing humans should demonstrate their highest cortisol concentrations in the morning and their lowest in the evening (Clements, 2012).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Clements, 2012 source
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- Premisecitation
Childhood adversity is associated with alterations in the inflammatory arm of the immune system.
“and the inflammatory arm of the immune system (Carpenter et al., 2010; Danese et al., 2011; Danese, Pariante, Caspi, Taylor, & Poulton, 2007; Slopen, Kubzansky, McLaughlin, & Koenen, 2013; Taylor, Lehman, Kiefe, & Seeman, 2006).”
Quote in the paperSubstantial claim0 of 3 sources checked - Premisecitation
Coordination of the sympathetic nervous system, HPA-axis, and inflammatory arm of the immune system in response to acute stress is essential to development, survival, and well-being.
“Coordination of the sympathetic nervous system (SNS), HPA-axis, and the inflammatory arm of the immune system, particularly in response to acute stress, is essential to development, survival, and well-being (Chrousos, 1995; Gunnar and Quevedo, 2007; Lopez-Duran et al., 2009).”
Quote in the paperSubstantial claim0 of 3 sources checked - Interpretationreasoning
A dose-response approach limits what is known to the overlap between heterogeneous adversity exposures.
“This approach limits what we know to the overlap between heterogeneous adversity exposure (See Figure 1), and few studies have considered the role of timing, thus limiting our understanding in the context of human development.”
Quote in the paperSubstantial claim- Rests on an assumption: Few studies have considered the role of timing in the association between childhood adversity and health.
- Premisecitation
Childhood trauma exposure during specific phases of development is important to later neurobiological functioning.
“An emerging literature also suggests childhood trauma exposure during specific phases of development is important to later neurobiological functioning (Andersen et al., 2008; Cowell et al., 2015; Gee and Casey, 2015; Kuhlman et al., 2015)”
Quote in the paperSubstantial claim0 of 3 sources checked - Premisecitation
Childhood adversity is associated with earlier mortality.
“as well as earlier mortality (Chen et al., 2016).”
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- Premisecitation
Threat perception by limbic structures causes the paraventricular nucleus to secrete CRH and vasopressin to the anterior pituitary.
“When structures in the limbic system perceive a threat (e.g., pain, extreme temperatures, aggressor), the paraventricular nucleus (PVN) of the hypothalamus secretes corticotropin releasing hormone (CRH) and vasopressin (AVP) to the anterior pituitary gland (Stratakis and Chrousos, 1995).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Stratakis and Chrousos, 1995 source
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- Premisecitation
Adaptive diurnal HPA-axis functioning has implications for immune functioning, growth, and sleep.
“Adaptive diurnal functioning of the HPA-axis has implications for other physiological processes such as immune functioning (Heim et al., 2002; Watts-English, Fortson, Gibler, Hooper, & De Bellis, 2006), growth (Kertes et al., 2008), sleep (Buckley and Schatzberg, 2005)”
Quote in the paperSubstantial claim0 of 3 sources checked - Interpretationreasoning
Subtypes of childhood adversity may have distinct physiological pathways that help explain developmental origins of disease.
“Thus, it is possible that subtypes of childhood adversity have distinct physiological pathways that elucidate developmental origins of disease.”
Quote in the paperSubstantial claim - Premisecitation
The HPA-axis and the inflammatory arm of the immune system respond and habituate differently to various types of stressors.
“Notably, the HPA-axis and inflammatory arm of the immune system respond and habituate differently to various types of stressors (Bowers et al., 2008; Kant et al., 1985; Kuhlman et al., 2014; Pacák, 1999; Pacák et al., 1998, 1995; Sheridan and McLaughlin, 2014; Weiner,”
Quote in the paperSubstantial claim0 of 3 sources checked - Premisecitation
Upregulations in the HPA-axis and inflammatory systems are central to the pathogenesis of stress-related illness.
“Intermediate phenotypes comprised of upregulations in these systems are thought to be central to the pathogenesis of stress-related illness (McEwen, 2013).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites McEwen, 2013 source
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- Premisecitation
Childhood adversity is associated with alterations in hypothalamic-pituitary-adrenal axis functioning.
“Childhood adversity is associated with alterations to the body’s physiological stress response systems, including the hypothalamic-pituitary-adrenal axis (HPA-axis) (Gunnar & Quevedo, 2007; Heim & Nemeroff, 2001)”
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The association between adversity and health has predominantly been tested as a dose-response relationship.
“To date, the association between adversity and health has predominantly been tested as a dose-response relationship (e.g., Anda et al., 2006; Chapman et al., 2007; Evans et al., 2013; Kessler et al., 2010).”
Quote in the paperSubstantial claim0 of 3 sources checked - Premisecitation
Abnormally low diurnal cortisol can indicate hypothalamic down-regulation of CRF/AVP secretion, possibly after repeated activation to chronic environmental stress.
“Abnormally low diurnal cortisol can be an indicator that the hypothalamus has down-regulated secretion of CRF/AVP to the pituitary (Aguilera, 2012), possibly following repeated activation to chronic environmental stress (Heim, Ehlert, & Hellhammer, 2000; Miller, Chen, & Zhou, 2007).”
Quote in the paperNot a substantial claim0 of 3 sources checked - Interpretationreasoning
Intracellular measures of inflammatory processes may be particularly useful in youth as a predictor of future risk for chronic inflammation.
“Intracellular measures of inflammatory processes may be particularly useful in youth as a predictor of future risk for chronic inflammation.”
Quote in the paperSubstantial claim - Premisecitation
Cumulative childhood maltreatment is associated with exaggerated inflammatory responses to acute stress.
“Cumulative childhood maltreatment is associated with exaggerated inflammatory responses to acute stress (Carpenter et al., 2010)”
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- Interpretationreasoning
Animal models of repeated social defeat may be useful for understanding potential effects of childhood adversities involving physical abuse or injury.
“Thus, we propose that animal models of the physiological consequences of RSD may be useful in understanding the potential effects of childhood adversities involving physical abuse or injury.”
Quote in the paperNot a substantial claim- Rests on an assumption: Well-characterized animal models of repeated social defeat, maternal separation, and chronic variable stress are valid analogs for the corresponding elements of human childhood adversity.
- Premisecitation
Childhood physical abuse exposure is associated with a multisystemic biological risk profile including HPA-axis and inflammatory markers.
“Consistent with this hypothesis, childhood physical abuse exposure is associated with a multisystemic biological risk profile (including both HPA-axis and inflammatory markers) (Friedman et al., 2015a).”
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- Premisecitation
Repeated social defeat causes rodents to release immature pro-inflammatory immune cells into circulation that promote inflammation at injury sites.
“RSD causes rodents to release immature, pro-inflammatory immune cells (CD11b+/Ly6C high) into circulation that serve to promote inflammation at the site of injury (Powell et al., 2013).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Powell et al., 2013 source
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- Interpretationreasoning
Maternal separation paradigms may serve as a useful animal model for understanding associations between disrupted caregiving and HPA-axis and inflammatory functioning.
“Thus, we propose that maternal separation paradigms may serve as a useful animal model for understanding the unique associations between disruptions in the caregiving environment and HPA-axis and inflammatory functioning.”
Quote in the paperNot a substantial claim- Rests on an assumption: Well-characterized animal models of repeated social defeat, maternal separation, and chronic variable stress are valid analogs for the corresponding elements of human childhood adversity.
- Premisecitation
Effective down-regulation of inflammation by glucocorticoids is essential to preventing persistently elevated inflammation.
“The effective down-regulation of inflammation by glucocorticoids is essential to preventing persistently elevated (Stark et al., 2001).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Stark et al., 2001 source
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- Premisecitation
Prolonged or chronic stress in humans can lead to glucocorticoid receptor insensitivity in immune cells.
“Similarly, prolonged or chronic stress in humans can lead to GR insensitivity, meaning that GRs in immune cells are not able to “hear” the inhibitory signals of glucocorticoids (Cohen et al., 2012; Miller et al., 2002).”
Quote in the paperSubstantial claim0 of 2 sources checked - Premisecitation
Child abuse resulting in pediatric traumatic brain injury is associated with elevated IL-4, IL-12, and IL-8.
“Child abuse that results in pediatric traumatic brain injury has also been associated with elevated IL-4, IL-12 (Amick et al., 2001), and IL-8 (Whalen et al., 2000).”
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In preclinical models, repeated acute stress causes glucocorticoid resistance in immune cells.
“In preclinical models, repeated acute stress has been shown to cause glucocorticoid resistance in immune cells (Avitsur et al., 2009; Engler et al., 2008).”
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A critical role of the HPA-axis is regulation of inflammation.
“A critical role of the HPA-axis is regulation of inflammation.”
Quote in the paperSubstantial claim - Premisecitation
The physiological consequences of repeated social defeat are robustly associated with structural changes in neural systems that modulate threat-sensitivity and anxiety-like behaviors.
“In addition, the physiological consequences of exposure to RSD are robustly associated with structural changes (e.g., atrophy, connectivity) to neural systems that modulate threat-sensitivity and anxiety-like behaviors (Reader et al., 2015).”
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- Premisecitation
The development of the repeated social defeat behavioral phenotype is mediated by immune cell derived IL-6.
“and the development of this behavioral phenotype is mediated by immune cell derived IL-6 (Hodes et al., 2014).”
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- Premisecitation
Exposure to bullying during childhood and adolescence is associated with elevated C-reactive protein in early and middle adulthood.
“Similarly, exposure to bullying during childhood and adolescence is associated with elevated CRP during early (Copeland et al., 2014) and middle adulthood (Takizawa et al., 2015)”
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Exposure to repeated social defeat leads to anxiety-like behavior in two-thirds of rodents.
“And indeed, exposure to RSD leads to anxiety-like behavior in two-thirds of rodents (Golden et al., 2011)”
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- Interpretationreasoning
Acute inflammatory changes are believed to occur adaptively in preparation for potential injuries from acute threat.
“These acute changes are believed to occur adaptively in preparation for potential injuries incurred as a result of acute threat.”
Quote in the paperNot a substantial claim - Premisecitation
Binding of glucocorticoids to glucocorticoid receptors in immune cells downregulates cytokine production.
“GRs can be found in immune cells and binding of glucocorticoids to the GRs downregulates cytokine production (Silverman et al., 2005).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Silverman et al., 2005 source
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- Premisecitation
Children and adults exposed to physical abuse demonstrate increased risk for anxiety disorders and a wide range of physical and behavioral distress.
“Consistent with these animal models, both children (Shackman et al., 2007) and adults (Stein et al., 1996) exposed to physical abuse demonstrate increased risk for anxiety disorders and a wide range of physical and behavioral distress.”
Quote in the paperSubstantial claim0 of 2 sources checked - Premisecitation
Inflammation increases in the context of psychosocial stress.
“Notably, inflammation also increases in the context of psychosocial stress (Steptoe et al., 2007).”
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- Premisecitation
Physical and sexual abuse are not consistently linked with elevated inflammation in adults after accounting for covariates such as BMI and smoking.
“Of note, physical and sexual abuse are not consistently linked with elevated inflammation in adults after accounting for covariates such as BMI and smoking (Bertone-Johnson et al., 2012)”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Bertone-Johnson et al., 2012 source
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- Premisecitation
Less naturally occurring maternal licking and grooming immediately after maternal separation corresponds to reduced hippocampal glucocorticoid receptor expression that presages increased hypothalamic CRH and exaggerated ACTH and glucocorticoid responses to stress in adulthood.
“In particular, less naturally occurring maternal licking and grooming behavior immediately following maternal separation corresponds reduced expression of glucocorticoid receptors in the hippocampus that presage increased expression of CRH in the hypothalamus and exaggerated ACTH and glucocorticoid responses to stress in adulthood (Liu et al., 1997).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Liu et al., 1997 source
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- Premisecitation
Infants and school-aged children exposed to frequent physical punishment demonstrate exaggerated cortisol responses to psychological stress.
“Infants (Bugental et al., 2003) and school-aged children (Kuhlman et al., 2014) exposed to frequent physical punishment demonstrate exaggerated cortisol responses to psychological stress.”
Quote in the paperSubstantial claim0 of 2 sources checked - Premisecitation
Repeated and prolonged maternal separation in rodent pups results in exaggerated sympathetic nervous system and HPA-axis responses to stress during adolescence and adulthood.
“Repeated and prolonged maternal separation in rodent pups results in exaggerated SNS and HPA-axis responses to stress during adolescence and adulthood (Kalinichev et al., 2002; Plotsky and Meaney, 1993).”
Quote in the paperSubstantial claim0 of 2 sources checked - Premisecitation
Suicide victims exposed to interpersonal violence as children exhibit elevated CSF cortisol among suicide attempters.
“suicide victims exposed to interpersonal violence as children exhibit elevated CSF cortisol among suicide attempters (Chatzittofis et al., 2013).”
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- Premisecitation
Youth exposed to sexual abuse exhibit elevated circulating plasma cortisol compared with controls.
“youth exposed to sexual abuse, which involves invasive physical contact and often injury, exhibit elevated circulating plasma cortisol compared to controls (Şimşek et al., 2015)”
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- Interpretationcitation
Childhood adversities vary in the degree to which they involve physical trauma, disruptions in caregiving, and unpredictability.
“We propose that childhood adversities vary in the degree to which they involve physical trauma, disruptions in caregiving, and unpredictability.”
Quote in the paperSubstantial claim - Premisecitation
Twelve-year-old children exposed to physical maltreatment by their mothers and who also have elevated depression symptoms have elevated C-reactive protein.
“For example, 12-year old children exposed to physical maltreatment by their mothers who also have elevated symptoms of depression have elevated CRP (Danese et al., 2011).”
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- Premisenone given
Repeated social defeat, maternal separation, and chronic variable stress paradigms each show evidence that HPA-axis and inflammatory responses undergo distinct alterations corresponding to diverging behavioral phenotypes.
“Each of these paradigms has shown evidence that both the HPA-axis and inflammatory response undergo distinct alterations that correspond to diverging behavioral phenotypes.”
Quote in the paperNot a substantial claim - Premisecitation
Childhood environments and experiences play a role in epigenetic regulation of many components of physiological stress response systems.
“Yet, in the past decade we have developed a much stronger appreciation for the role childhood environments and experiences in the epigenetic regulation of many components of physiological stress response systems (Anacker et al., 2014; Tyrka et al., 2013).”
Quote in the paperSubstantial claim0 of 2 sources checked - Interpretationreasoning
When multiple adversities co-occur, their effects may converge to produce multi-systemic vulnerability to disease across the lifespan.
“In the face of co-occurrence of multiple adversities, which is more common than not, these effects may converge for multi-systemic vulnerability to disease across the lifespan.”
Quote in the paperNot a substantial claim- Rests on an assumption: Different types of childhood adversity commonly co-occur.
- Premisecitation
The inflammatory response in newborns has been characterized as hyporesponsive.
“The inflammatory response in newborns has been characterized as hyporesponsive.”
Quote in the paperNot a substantial claim - Premisecitation
Adult offspring of Holocaust survivors reporting more exposure to emotional abuse and neglect exhibit elevated urinary cortisol.
“and adult offspring of Holocaust survivors reporting more exposure to emotional abuse and neglect exhibit elevated urinary cortisol (Yehuda et al., 2000).”
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- Interpretationreasoning
This attenuated early innate immunity may protect against excessive inflammation that can compromise development and health.
“This may protect against excessive inflammation that can compromise development and health.”
Quote in the paperNot a substantial claim - Interpretationreasoning
Inflammatory processes may continue to change throughout adolescence as a function of pubertal development.
“Given that gonadal hormones are known to modulate immune functioning, inflammatory processes may continue to change throughout adolescence as a function of pubertal development.”
Quote in the paperSubstantial claim- Rests on an assumption: Circulating immune cells, including macrophages, and lymphoid tissue cells express receptors for gonadal hormones.
- Premisecitation
Experiencing multiple types of maltreatment before adulthood is associated with elevated C-reactive protein, fibrinogen, and proinflammatory cytokines.
“Overall, experiencing multiple types of maltreatment before adulthood was associated with elevated CRP, fibrinogen, and proinflammatory cytokines (Coelho et al., 2014).”
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- Interpretationreasoning
The combined animal and human literature suggests distinct underlying processes through which co-occurring elements of childhood adversity lead to a similar intermediate phenotype of elevated inflammation and atypical HPA-axis functioning.
“However, the combined interpretation of the existing animal and human literature suggests that there may be distinct underlying processes through which co-occuring elements of childhood adversity lead to a similar intermediate phenotype, elevated inflammation and atypical functioning of the HPA-axis.”
Quote in the paperSubstantial claim- Rests on an assumption: Elevated diurnal cortisol and inflammation serve as intermediate phenotypes linking childhood adversity to later disease.
- Interpretationreasoning
Animals deprived of maternal nurturing behaviors will demonstrate impaired ability to down-regulate physiological responses to stress once activated.
“This means that animals deprived of maternal nurturing behaviors will demonstrate impaired ability to down-regulate physiological responses to stress once activated.”
Quote in the paperSubstantial claim - Premisecitation
Estrogen increases secretion of IL-6 and IL-8 in dendritic cells derived from monocytes.
“For instance, estrogen has been shown to increase secretion of IL-6 and IL-8 in dendritic cells derived from monocytes (Bengtsson et al., 2004)”
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- Interpretationreasoning
Early innate immunity is characterized by attenuated inflammatory responses compared with adults.
“Overall, early innate immunity may be characterized by attenuated inflammatory responses relative to those found in adults.”
Quote in the paperNot a substantial claim - Interpretationreasoning
Disruptions in the caregiving environment during childhood may interfere with effective down-regulation of glucocorticoid production, including negative feedback following acute stress or pharmacological challenge, diurnal regulation, and tonic regulation of the axis.
“Disruptions in the caregiving environment during childhood may interfere with the effective down-regulation of glucocorticoid production, including negative feedback following acute stress or pharmacological challenge, diurnal, and tonic regulation of the axis.”
Quote in the paperNot a substantial claim - Interpretationcitation
Disrupted caregiving may result in impaired negative feedback within immune cells via increased intracellular inflammatory gene expression and decreased glucocorticoid receptor sensitivity, promoting inflammatory cytokine production despite elevated glucocorticoids.
“Disrupted caregiving may also result in impaired negative feedback within immune cells via increased intracellular inflammatory gene expression and decreased glucocorticoid receptor sensitivity which promotes production of inflammatory cytokines despite the presence of elevated glucocorticoids (Cole et al., 2012).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Cole et al., 2012 source
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- Premisecitation
Maternal depression during early childhood robustly predicts elevated tonic cortisol during middle childhood.
“Maternal depression during early childhood robustly predicts elevated tonic cortisol during middle childhood (Ashman et al., 2002; Essex et al., 2002).”
Quote in the paperNot a substantial claim0 of 2 sources checked - Premisecitation
Impaired down-regulation of cortisol appears to persist into adulthood.
“This pattern of impaired down-regulation of cortisol also appears to persist into adulthood.”
Quote in the paperSubstantial claim - Interpretationreasoning
There may be windows of susceptibility during which exposure to adversity results in differential influences on inflammatory outcomes.
“The major differences in inflammatory processes among infants, youth, and adults point to the possibility that there are windows of susceptibility during which exposure to adversity may result in differential influences on inflammatory outcomes.”
Quote in the paperSubstantial claim - Premisecitation
Estrogen receptor-α treatment inhibits TNF-α and IL-6.
“whereas estrogen receptor-α treatment inhibits TNF-α and IL-6 (Tiwari-Woodruff et al., 2007).”
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- Interpretationreasoning
An unpredictable environment may be particularly associated with elevated basal cortisol and inflammatory markers throughout the day due to increased CNS-originating threat response vigilance.
“Finally, an unpredictable environment may be particularly associated with elevated basal cortisol and markers of inflammation throughout the day due to increased vigilance of the threat response system originating from the central nervous system.”
Quote in the paperNot a substantial claim- Rests on an assumption: The frequency and magnitude of threat response system activation are reflected in cortisol and inflammatory markers.
- Premisecitation
Adults who lost a parent during childhood demonstrated higher cortisol throughout the day compared with adults who never experienced separation from their parents for longer than two weeks.
“For example, adults who lost a parent during childhood demonstrated higher cortisol throughout the day compared with adults who never experienced separation from their parents for longer than two weeks (Nicolson, 2004).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Nicolson, 2004 source
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- Premisecitation
When accounting for other types of early trauma, exposure to emotional abuse is specifically associated with impaired recovery of the HPA-axis to acute psychosocial stress in adolescents.
“And finally, when accounting for other types of early trauma, exposure to emotional abuse was specifically associated with impaired recovery of the HPA-axis to acute psychosocial stress in adolescents (Kuhlman et al., 2015).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Kuhlman et al., 2015
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- Interpretationreasoning
Mounting a robust inflammatory response in some contexts during early development may be adaptive.
“Despite the detrimental effects that high levels of inflammation can have on the developing organism, mounting a robust inflammatory response in some contexts during early development may be adaptive.”
Quote in the paperNot a substantial claim- Rests on an assumption: Innate immunity is the primary defense against infection in early life because adaptive immunity takes longer to develop.
- Interpretationreasoning
Having the capacity to mount a robust inflammatory response to particular microbial challenges during the neonatal period likely increases chances of survival.
“As such, having the capacity to mount a robust inflammatory response to particular microbial challenges during the neonatal period likely increases chances of survival.”
Quote in the paperNot a substantial claim- Rests on an assumption: Innate immunity is the primary defense against infection in early life because adaptive immunity takes longer to develop.
- Interpretationreasoning
The transition into adolescence and puberty may also be a sensitive period during which adversity exposure can have enduring effects on later HPA-axis functioning.
“This suggests that the transition into adolescence and puberty may also be a sensitive period during which adversity exposure can have enduring effects on later HPA-axis functioning.”
Quote in the paperSubstantial claim - Premisecitation
Maternal separation during childhood is associated with exaggerated cortisol awakening response into adulthood.
“Maternal separation during childhood is associated with exaggerated CAR into adulthood (Kumari, Head, Bartley, Stansfeld, & Kivimaki, 2013).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Kumari, Head, Bartley, Stansfeld, & Kivimaki, 2013 source
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- Interpretationnone given
CVS is proposed as a plausible translational model for exposure to an unpredictable developmental environment.
“Thus, we propose CVS as a plausible translational model for exposure to an unpredictable developmental environment.”
Quote in the paperNot a substantial claim - Premisecitation
Maternal care in infancy contributes to epigenetic regulation of the glucocorticoid receptor in the hippocampus and in peripheral immune cells.
“Maternal care in infancy contributes to epigenetic regulation of the glucocorticoid receptor in the hippocampus (Anacker et al., 2014; McGowan et al., 2009) as well as in peripheral immune cells (Miller et al., 2011; Tyrka et al., 2012).”
Quote in the paperSubstantial claim0 of 3 sources checked - Interpretationcitation
Infancy may be a sensitive period during which adversity exposure has particularly potent and/or enduring effects on HPA-axis development, especially in the absence of a nurturing caregiver.
“Collectively, these studies point to infancy as a possible sensitive period, especially in the absence of a nurturing caregiver.”
Quote in the paperSubstantial claim - Premisecitation
Social deprivation during early childhood (ages 0-2) is associated with flat diurnal cortisol slopes throughout the day.
“For example, social deprivation during early childhood (ages 0–2) is associated with flat diurnal cortisol slopes throughout the day (Koss et al., 2014).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Koss et al., 2014 source
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- Premisecitation
Human studies of different types of disruptions in the caregiving environment fairly consistently observe impaired regulation of the HPA-axis in childhood.
“Indeed, human studies of different types of disruptions in the caregiving environment fairly consistently observe impaired regulation of the HPA-axis in childhood.”
Quote in the paperSubstantial claim - Interpretationreasoning
Individuals exposed to various forms of disrupted caregiving would demonstrate impaired HPA-axis negative feedback observable during regulation from the cortisol awakening response, acute stress paradigms, elevated diurnal cortisol, and non-suppression following dexamethasone administration.
“Within this translational model, we would expect that individuals exposed to various forms of disrupted caregiving would demonstrate impaired HPA-axis negative feedback that can be observed during regulation from CAR, acute stress paradigms, elevated diurnal cortisol, and non-suppression following Dexamethasone administration.”
Quote in the paperNot a substantial claim - Interpretationreasoning
Some types of disrupted caregiving may be associated with elevated peripheral markers of inflammation.
“Some types of disrupted caregiving may be associated with elevated peripheral markers of inflammation.”
Quote in the paperNot a substantial claim - Premisecitation
Low maternal warmth during early childhood prospectively predicts impaired down-regulation of cortisol following peak response to acute psychological stress.
“Similarly, low maternal warmth during early childhood prospectively predicts impaired down-regulation of cortisol following peak response to acute psychological stress (Kuhlman et al., 2014).”
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- Premisecitation
IL-12 responses to bacterial challenge in monocytes are positively correlated with age from birth to age 8 years.
“Also, IL-12 responses to bacterial challenge in monocytes are positively correlated with age from birth to age 8 years (Härtel et al., 2005).”
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- Premisecitation
Innate immunity continues to mature through childhood.
“Innate immunity continues to mature through childhood, although few studies directly test this.”
Quote in the paperSubstantial claim0 of 2 sources checked - Premisecitation
Estrogen's modulation of inflammatory processes is complex, with effects depending on cell type, target organ, estrogen concentration, and expression of estrogen receptors.
“Prior work has shown estrogen to be both anti- and pro-inflammatory and its effects may depend on a variety of factors, such as cell type, target organ, estrogen concentration, and expression of estrogen receptors (Straub, 2007).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Straub, 2007 source
Not checked in the free run.
- Premisecitation
Maternal depression is associated with disengaged and negative parenting behaviors.
“In addition, maternal depression is associated with disengaged and negative parenting behaviors (Lovejoy et al., 2000).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Lovejoy et al., 2000 source
Not checked in the free run.
- Interpretationreasoning
Physical trauma may be associated with robust threat response activation, leading to exaggerated HPA-axis responses to acute stress and elevated inflammation.
“Specifically, physical trauma may be associated with robust activation of the threat response system leading to exaggerated HPA-axis responses to acute stress and elevated inflammation.”
Quote in the paperNot a substantial claim - Premisecitation
Inflammatory cytokines play a role in early neural development.
“Specifically, inflammatory cytokines play a role in early neural development (Stolp, 2013; Yirmiya and Goshen, 2011)”
Quote in the paperSubstantial claim0 of 2 sources checked - Premisecitation
Elevated inflammatory cytokines can have persistent negative effects on brain and behavior in rodents.
“rodent studies indicate that elevated inflammatory cytokines can have persistent negative effects on brain and behavior.”
Quote in the paperSubstantial claim - Interpretationreasoning
Adversity exposure during different periods of development may differentially impact the HPA-axis and immune system.
“Adversity exposure during different periods of development may differentially impact these systems.”
Quote in the paperSubstantial claim - Premisecitation
Experimentally-induced systemic inflammation during infancy leads to neuronal loss and delayed myelination for up to a week.
“For instance, experimentally-induced systemic inflammation during infancy leads to neuronal loss and delayed myelination for up to a week (Cardoso et al., 2015).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Cardoso et al., 2015 source
Not checked in the free run.
- Premisenone given
Existing models for how early adversity confers risk for poor health mostly do not consider the timing of adversity exposure.
“In addition to neglecting the distinct physiological effects of adversity type, existing models for how early adversity confers risk for poor health, for the most part, do not consider the role of timing of adversity exposure.”
Quote in the paperNot a substantial claim - Premisecitation
Adult men who experienced the loss of a parent via death or desertion during childhood exhibit larger responses to the Dex/CHR test.
“Adult men who experienced the loss of a parent via death or desertion during childhood exhibit larger responses to the Dex/CHR test (Tyrka et al., 2008)”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Tyrka et al., 2008 source
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- Premisecitation
The association between early adversity exposure and inflammation has been well-documented.
“Although the association between early adversity exposure and inflammation has been well-documented (See Baumeister et al., 2016; Miller et al., 2011 for review)”
Quote in the paperSubstantial claim0 of 2 sources checked - Interpretationcitation
Adversity exposure very early in life, from birth to early childhood, may prime immune cells to have a pro-inflammatory tendency, resulting in an intermediate phenotype of enduring elevated inflammation.
“There is some empirical evidence suggesting that adversity exposure very early in life, from birth to early childhood, may prime immune cells to have a pro-inflammatory tendency, resulting in an intermediate phenotype of enduring elevated inflammation.”
Quote in the paperSubstantial claim - Premisecitation
Chronic family stress is related to decreased glucocorticoid receptor sensitivity in immune cells among adolescent females.
“For example, chronic peer stress has been related to enhanced cytokine production in response to bacterial challenge and chronic family stress was related to decreased glucocorticoid receptor sensitivity in immune cells among adolescent females (Ehrlich et al., 2016).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Ehrlich et al., 2016 source
Not checked in the free run.
- Interpretationreasoning
Functioning of HPA-axis and immune systems varies according to timing of adversity.
“The relative immaturity of the HPA-axis and immune systems during infancy and their continued development through childhood and adolescence point to the possibility that functioning of these systems vary according to timing of adversity.”
Quote in the paperSubstantial claim - Premisecitation
Nurturing parenting can buffer the effect of other types of stress.
“Evidence supporting this notion already exists in maternal buffering of stress, suggesting that nurturing parenting can buffer the effect of other types of stress (Gunnar, 1998; Hagan et al., 2010; Hostinar et al., 2014).”
Quote in the paperSubstantial claim0 of 3 sources checked - Premisecitation
Continued exposure to high cortisol may eventually lead to glucocorticoid insensitivity.
“For instance, continued exposure to high cortisol may eventually lead to glucocorticoid insensitivity (Cohen et al., 2012; Miller et al., 2002)”
Quote in the paperNot a substantial claim0 of 2 sources checked - Interpretationnone given
Initial studies show an association between adversity during adolescence and lower cortisol and elevated inflammation.
“Adversity during adolescence may also be an important time when the social environment becomes biologically embedded, with initial studies showing an association between adversity during adolescence and lower cortisol and elevated inflammation.”
Quote in the paperNot a substantial claim - Interpretationreasoning
Distinct adversity subtypes reveal different underlying biological adaptations.
“However, distinct adversity subtypes reveal different underlying biological adaptations.”
Quote in the paperSubstantial claim - Premisecitation
In adulthood, a subsequent stressor can lead activated microglia to secrete more pro-inflammatory cytokines.
“Notably, in adulthood, a subsequent stressor can lead these activated microglia to secrete more pro-inflammatory cytokines (Bilbo, 2013).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Bilbo, 2013 source
Not checked in the free run.
- Interpretationnone given
Physical abuse and injury may be uniquely associated with exaggerated activation of the HPA-axis and inflammatory system during childhood, which persists as elevated inflammation and adrenal insensitivity to ACTH in adulthood.
“For example, physical abuse and injury may be uniquely associated with exaggerated activation of the HPA-axis and inflammatory system during childhood, which persists as elevated inflammation and adrenal insensitivity to ACTH in adulthood.”
Quote in the paperNot a substantial claim - Interpretationreasoning
Adversity during adolescence may be an important time when the social environment becomes biologically embedded.
“Adversity during adolescence may also be an important time when the social environment becomes biologically embedded, with initial studies showing an association between adversity during adolescence and lower cortisol and elevated inflammation.”
Quote in the paperSubstantial claim - Interpretationcitation
Microglia in the CNS and monocytes/macrophages in the periphery may develop a pro-inflammatory tendency.
“Specifically, microglia in the central nervous system and monocytes/macrophages in the periphery may develop a pro-inflammatory tendency (Miller et al., 2011).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Miller et al., 2011 source
Not checked in the free run.
- Interpretationnone given
There is a tendency for non-specific childhood adversity to be correlated with up-regulated HPA-axis output and elevated inflammation.
“Overall, there is a tendency for non-specific childhood adversity to be correlated with up-regulated HPA-axis output and elevated inflammation.”
Quote in the paperNot a substantial claim - Interpretationnone given
Disruptions in the caregiving environment are associated with impaired glucocorticoid regulation.
“We also find evidence that disruptions in the caregiving environment are associated with impaired glucocorticoid regulation, and that repeated exposure to unpredictable stress may be associated with more frequent activation of the stress response systems, perhaps driven by increased neural sensitivity to threat.”
Quote in the paperSubstantial claim - Premisecitation
Individuals vary in their sensitivity to stress in the developmental environment.
“It is also becoming more and more clear that individuals vary in their sensitivity to stress in the developmental environment (Boyce and Ellis, 2005; Ellis et al., 2005; Ellis and Boyce, 2008; Obradović et al., 2010).”
Quote in the paperSubstantial claim0 of 3 sources checked- cites Boyce and Ellis, 2005 source
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- cites Ellis et al., 2005
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- cites Ellis and Boyce, 2008
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- Premisecitation
Chronic stress paradigms fail if the gap between stressors is too long.
“Presumably, this is because chronic stress paradigms fail if the gap between stressors is too long (Golden et al., 2011).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Golden et al., 2011 source
Not checked in the free run.
- Premisecitation
Chronic peer stress is related to enhanced cytokine production in response to bacterial challenge among adolescent females.
“For example, chronic peer stress has been related to enhanced cytokine production in response to bacterial challenge and chronic family stress was related to decreased glucocorticoid receptor sensitivity in immune cells among adolescent females (Ehrlich et al., 2016).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Ehrlich et al., 2016 source
Not checked in the free run.
- Interpretationcitation
Less adversity during early adolescence may have long-term effects on inflammation.
“This points to the possibility that less adversity during early adolescence may have long-term effects on inflammation.”
Quote in the paperSubstantial claim - Premisecitation
A 7-week family-oriented psychosocial intervention implemented among low-SES, 11-year-old youth resulted in lower markers of inflammation when youth were 19-years-old relative to a waitlist control.
“An intervention study also showed that relative to a waitlist control, a 7-week family-oriented psychosocial intervention implemented among low-SES, 11-year-old youth resulted in lower markers of inflammation when youth were 19-years-old (Miller et al., 2014).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Miller et al., 2014 source
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- Premisecitation
Maltreated youth demonstrate less symmetry between sympathetic and HPA-axis responses to acute stress than non-maltreated youth.
“Maltreated youth demonstrate less symmetry between sympathetic and HPA-axis responses to acute stress than non-maltreated youth (Gordis et al., 2008).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Gordis et al., 2008 source
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- Premisecitation
Socially-evaluative challenges are particularly salient to the HPA-axis.
“For example, we know that socially-evaluative challenges are particularly salient to the HPA-axis (Dickerson and Kemeny, 2004).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Dickerson and Kemeny, 2004 source
Not checked in the free run.
- Interpretationreasoning
The timing of adversity may explain variation in the links between different childhood adversities and HPA-axis dysregulation and elevated inflammation.
“and that timing of adversity may contribute to variation in these linkages”
Quote in the paperSubstantial claim - Premisecitation
2-year-old children whose parents reported higher cumulative stress during the child's life exhibited heightened TNF-α responses to an allergen.
“For instance, 2-year-old children whose parents reported higher cumulative stress during the child’s life exhibited heightened TNF-α responses to an allergen (Wright et al., 2004).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Wright et al., 2004 source
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- Premisecitation
Family chaos is associated with greater stimulated proinflammatory cytokine production among 13-16 year old adolescents.
“Likewise, family chaos has also been associated with greater stimulated proinflammatory cytokine production among 13–16 year old adolescents (Schreier et al., 2014).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Schreier et al., 2014 source
Not checked in the free run.
- Interpretationreasoning
Glucocorticoid receptor insensitivity may contribute to persistently elevated cortisol observed past infancy and into childhood.
“This may contribute to the persistently elevated cortisol observed past infancy and into childhood.”
Quote in the paperSubstantial claim - Premisecitation
Different types of stress vary in their salience to key biological systems thought to mediate stress and negative health outcomes.
“Yet, a parallel line of experimental research has demonstrated that different types of stress vary in their salience to the key biological systems thought to mediate stress and negative health outcomes (e.g., Dickerson, Gable, Irwin, Aziz, & Kemeny, 2009; Dickerson & Kemeny, 2004; Kuhlman et al., 2014; Lopez-Duran, Hajal, Olson, Felt, & Vazquez, 2009).”
Quote in the paperSubstantial claim0 of 3 sources checked - Interpretationreasoning
Repeated exposure to unpredictable stress may be associated with more frequent activation of the stress response systems, perhaps driven by increased neural sensitivity to threat.
“We also find evidence that disruptions in the caregiving environment are associated with impaired glucocorticoid regulation, and that repeated exposure to unpredictable stress may be associated with more frequent activation of the stress response systems, perhaps driven by increased neural sensitivity to threat.”
Quote in the paperNot a substantial claim - Interpretationreasoning
Adversity during early life and puberty might have greater long-term consequences for inflammatory processes.
“Likewise, given the reliance of the organism on innate immunity very early in life and the flux of gonadal hormones during puberty, we suggested that adversity during these periods might have greater long-term consequences for inflammatory processes.”
Quote in the paperSubstantial claim - Premisecitation
The Maltreatment and Abuse Chronology of Exposure (MACE) is the first measure to directly assess timing of childhood maltreatment exposure within a developmental framework.
“In fact, the Maltreatment and Abuse Chronology of Exposure (MACE) (Teicher and Parigger, 2015) is the first measure to directly assess timing of childhood maltreatment exposure within a developmental framework.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Teicher and Parigger, 2015 source
Not checked in the free run.
- Premisecitation
Early adversity, including maternal separation and early infection, during infancy results in larger, activated microglia in rodents.
“In particular, rodent studies have demonstrated that early adversity, including maternal separation and early infection, during infancy results in larger, activated microglia, resident immune cells in the brain that secrete inflammatory cytokines (Bilbo, 2013; Gracia-Rubio et al., 2015).”
Quote in the paperSubstantial claim0 of 2 sources checked - Premisecitation
Lower SES as indicated by parental occupation during a child's first five years of life is associated with exaggerated inflammatory responses to pathogens.
“Lower SES as indicated by parental occupation during a child’s first five years of life has also been associated with exaggerated inflammatory responses to pathogens (Miller et al., 2009).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Miller et al., 2009
Not checked in the free run.
- Interpretationreasoning
Very early life may be a period during which adversity can program immune cells.
“Very early life may be a period during which adversity can program immune cells.”
Quote in the paperSubstantial claim - Interpretationcitation
Parental divorce may not have the same biological salience to the developing child if the subjective quality of the caregiving relationships remains intact.
“For example, parental divorce is an “adverse childhood event,” but may not have the same biological salience to the developing child if the subjective quality of the caregiving relationships remains intact.”
Quote in the paperSubstantial claim - Interpretationreasoning
Different types of childhood adversity may produce dysregulated HPA-axis function and increased inflammation through separate mechanisms.
“Different childhood adversities may lead to dysregulated HPA-axis functioning and elevated inflammation via distinct underlying mechanisms”
Quote in the paperSubstantial claim - Premisecitation
Early family stress is indirectly associated with circulating levels of inflammation through adiposity and smoking at 22-25 years of age.
“In support of this notion, a longitudinal study involving contemporaneous measured early family stress during the first five years of life found that early family stress was indirectly associated with circulating levels of inflammation through adiposity and smoking at 22–25 years of age (Raposa et al., 2014a).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Raposa et al., 2014a
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- Premisecitation
Adversity during middle childhood (6-8 years) is related to higher CRP at both 10 and 15 years.
“Slopen and colleagues (2013) also found that adversity during middle childhood (6–8 years) was related to higher CRP at both 10 and 15 years.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Slopen et al., 2013 source
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- Premisecitation
Childhood adversity predicts lifelong mental and physical illness in a dose-response manner.
“We know from several large epidemiological studies that childhood adversity predicts lifelong mental and physical illness in a dose-response manner (Caspi et al., 2014; Chapman et al., 2007; Kessler et al., 2010; Vachon, Krueger, Rogosch, & Cicchetti, 2015).”
Quote in the paperSubstantial claim0 of 3 sources checked - Interpretationcitation
It is more likely that individuals carry genetic vulnerability to specific intermediate phenotypes within a complex system when exposed to relevant life stressors.
“it is more likely that individuals carry genetic vulnerability to specific intermediate phenotypes within a complex system when exposed to relevant life stressors (See for example Tyrka et al., 2009).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Tyrka et al., 2009 source
Not checked in the free run.
- Interpretationnone given
The CVS paradigm is particularly useful for understanding the physiological sequelae of growing up in an unpredictable environment.
“the CVS paradigm for understanding the physiological sequelae of growing up in an unpredictable environment”
Quote in the paperNot a substantial claim- Rests on an assumption: The CVS paradigm is a valid model of growing up in an unpredictable environment.
- Premisecitation
Each of these genetic risk factors has distinct connections to HPA-axis function and inflammatory activity.
“It is notable that each of these identified risk factors has distinct links to functioning of the HPA-axis and inflammatory activity.”
Quote in the paperNot a substantial claim0 of 2 sources checked - Premisecitation
Evidence supports that specific genetic risk factors can predispose an individual to psychopathology when life stress increases.
“there is evidence to support that specific genetic risk factors can predispose an individual to psychopathology in the presence of increasing life stress”
Quote in the paperNot a substantial claim0 of 2 sources checked - Interpretationcitation
Heterogeneity in adversity exposure in previous samples may explain why gene-by-environment associations have been inconsistently replicated.
“In fact, heterogeneity in adversity exposure in previous samples may explain inconsistent replication of gene-by-environment associations (Kim-Cohen et al., 2006; Munafò et al., 2009).”
Quote in the paperNot a substantial claim0 of 2 sources checked - Interpretationreasoning
Within the present model, some individuals exposed to specific types of adversity during development are likely more vulnerable than others.
“Thus within the present model, it is likely that some individuals exposed to specific types of adversity during development may be more vulnerable than others.”
Quote in the paperNot a substantial claim
- May combine two claims. 34
- Classified as probably not a substantial claim. 26
May combine two claims.
PremisecitationAcceleration of cortisol increase after stress may reflect the intensity of excitatory input into the axis from the limbic system, whereas cortisol regulation after peak more likely reflects glucocorticoid receptor density and sensitivity in the hippocampus.
“For example, acceleration of cortisol increase following stress could reflect the intensity of excitatory input into the axis from the limbic system, whereas cortisol regulation following peak more likely reflects the density and sensitivity of GRs, primarily in the hippocampus (Sapolsky, Meaney, & McEwen, 1985).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Sapolsky, Meaney, & McEwen, 1985 source
Not checked in the free run.
May combine two claims.
PremisecitationAbnormally high diurnal cortisol can indicate chronic hypothalamic CRH/AVP hypersecretion, pituitary ACTH hypersecretion, or repeated activation of the acute stress system.
“Abnormally high diurnal cortisol can be an indicator of several dysregulations in the axis; for example, this could indicate chronic hypersecretion of CRH/AVP by the hypothalamus, or hypersecretion of ACTH by the pituitary (Aguilera, 2012), or repeated activation of the acute stress system (Kidd et al., 2014).”
Quote in the paperNot a substantial claim0 of 2 sources checked- cites Aguilera, 2012
Not checked in the free run.
- cites Kidd et al., 2014 source
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Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
Premisenone givenGlucocorticoids are essential to the maintenance, duration, and down-regulation of the stress response and regulate CRH and ACTH secretion.
“Glucocorticoids are essential to the maintenance, duration, and down-regulation of the stress response, regulating CRH secretion from the hypothalamus and ACTH secretion by the pituitary.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationBinding of glucocorticoids to glucocorticoid receptors in the hippocampus is associated with regulation of the acute stress response.
“Binding of glucocorticoids to GRs in the hippocampus is associated with regulation of the acute stress response (Aguilera, 2012; De Kloet, 1991; Sapolsky et al., 2000; Smith & Vale, 2006).”
Quote in the paperNot a substantial claim0 of 3 sources checked- cites Aguilera, 2012
Not checked in the free run.
- cites De Kloet, 1991
Not checked in the free run.
- cites Sapolsky et al., 2000
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
PremisecitationThe HPA-axis maintains homeostasis and promotes adaptation to environmental stress through a hormonal cascade.
“The purpose of the HPA-axis is to maintain homeostasis and promote successful adaptation to environmental stress through a complex hormonal cascade (Aguilera, 2012; Selye, 1950).”
Quote in the paperNot a substantial claim0 of 2 sources checked- cites Aguilera, 2012
Not checked in the free run.
- cites Selye, 1950
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
PremisecitationThe cortisol awakening response reflects a mounting of physiological resources for the day and appears to measure adrenal sensitivity to ACTH.
“CAR is believed to reflect a mounting of physiological resources to meet the demands of the day (Adam and Gunnar, 2001), and also appears to be a measure of adrenal sensitivity to ACTH (Clow et al., 2010).”
Quote in the paperNot a substantial claim0 of 2 sources checked- cites Adam and Gunnar, 2001
Not checked in the free run.
- cites Clow et al., 2010 source
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationACTH stimulates the adrenal gland to increase production and release of glucocorticoids.
“ACTH stimulates the adrenal gland to increase production and release of glucocorticoids (cortisol in humans) (See Gunnar & Vazquez, 2006).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Gunnar & Vazquez, 2006
Not checked in the free run.
Probably not a substantial claim: may not pass S4 (based).
Interpretationnone givenThe biologically salient and distinguishable elements of adversity are physical trauma, disrupted caregiving, and unpredictable environment.
“The biologically salient and distinguishable elements of adversity we identify are: physical trauma, disrupted caregiving, and unpredictable environment.”
Quote in the paperNot a substantial claimMay combine two claims.
InterpretationreasoningTaken together, exposure to physical abuse and trauma during childhood exaggerates both inflammatory activity and HPA-axis reactivity to stress until adolescence.
“Taken together, exposure to physical abuse and trauma during childhood exaggerate both inflammatory activity and HPA-axis reactivity to stress until adolescence.”
Quote in the paperSubstantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationC-reactive protein concentrations greater than 3.0 mg/L are considered reliably predictive of cardiovascular disease risk.
“concentrations greater than 3.0 mg/L are considered reliably predictive of cardiovascular disease risk (See Ridker, 2003 for review).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Ridker, 2003 source
Not checked in the free run.
May combine two claims.
PremisecitationMeasurement limited to circulating peripheral cytokines is criticized for failing to localize the source of inflammatory cytokines and for sensitivity to confounders including SES, BMI, age, and sex.
“Measurement limited to circulating peripheral cytokines is often criticized for failing to localize the source of inflammatory cytokines and for being sensitive to several confounding factors, including SES, BMI, age, and sex (M.-F. O’Connor et al., 2009).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites M.-F. O’Connor et al., 2009
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PremisecitationAnimals injured during repeated social defeat exhibit glucocorticoid-resistant immune cells, systemic increases in glucocorticoids, exaggerated inflammatory responses, and increased pro-inflammatory gene expression in immune cells.
“Animals that sustain an injury during attack by the aggressor (Merlot et al., 2003) exhibit glucocorticoid resistant immune cells, systemic increases in glucocorticoids, exaggerated inflammatory responses (Avitsur et al., 2001; Stark et al., 2001), and increases in pro-inflammatory gene expression in immune cells (Powell et al., 2013).”
Quote in the paperSubstantial claim0 of 3 sources checkedMay combine two claims.
InterpretationreasoningWell-characterized animal models may serve as useful analogs for child adversity elements and provide causal models for distinct pathways from developmental stress to disease.
“To better understand the downstream physiological consequences, we consider well-characterized animal models that may serve as useful analogs for these child adversity elements and provide informative causal models for understanding the distinct pathways from different types of developmental stress to disease.”
Quote in the paperSubstantial claim- Rests on an assumption: Well-characterized animal models of repeated social defeat, maternal separation, and chronic variable stress are valid analogs for the corresponding elements of human childhood adversity.
May combine two claims.
PremisecitationPhysical trauma, caregiving disruption, and unpredictability are each salient to central nervous system development with implications for learning and downstream physiological adaptations.
“Each of these elements has been identified as salient to the development of the central nervous system with implications for learning and downstream physiological adaptations (Gunnar and Vazquez, 2006; McLaughlin et al., 2014b; Teicher et al., 2003).”
Quote in the paperSubstantial claim0 of 3 sources checked- cites Gunnar and Vazquez, 2006
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- cites McLaughlin et al., 2014b
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- cites Teicher et al., 2003 source
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May combine two claims.
InterpretationreasoningMaternal separation may be more closely linked to impaired regulation of the stress response once initiated, whereas physical trauma appears linked to exaggerated activation of stress response systems.
“Yet, maternal separation may be more closely linked to impaired regulation of the stress response once initiated whereas physical trauma appears to be linked to exaggerated activation of stress response systems.”
Quote in the paperSubstantial claimMay combine two claims.
PremisecitationChildhood abuse significantly accelerates biological aging and all-cause mortality.
“Indeed, childhood abuse significantly accelerates biological aging (Tyrka et al., 2010) and all-cause mortality (Chen et al., 2016).”
Quote in the paperNot a substantial claim0 of 2 sources checkedMay combine two claims.
PremisecitationThreat perception causes the sympathetic nervous system to release noradrenaline, which mobilizes stem cells from bone marrow and activates immune gene transcription in white blood cells, organs, and tissues.
“When threat is perceived, the SNS releases noradrenaline, which promotes mobilization of stem cells from the bone marrow and activates immune gene transcription within white blood cells, organs, and tissues (Irwin and Cole, 2011).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Irwin and Cole, 2011 source
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May combine two claims.
PremisecitationPhysical trauma is linked to elevated circulating markers of inflammation and inflammatory diseases.
“Several studies indicate a link between physical trauma and both elevated circulating markers of inflammation and inflammatory diseases (Friedman et al., 2015b).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Friedman et al., 2015b
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Probably not a substantial claim: may not pass S2 (checkable).
InterpretationreasoningSimultaneous examination of circulating, cellular, and intracellular measurements of inflammatory processes may drive progress in understanding environmental and psychological stress effects on this system.
“Further, the simultaneous examination of circulating, cellular, and intracellular measurements of inflammatory processes may drive progress in our understanding of environmental and psychological stress on this system.”
Quote in the paperNot a substantial claimClassified as probably not a substantial claim.
PremisecitationAllostatic load is a process through which failure to adapt to repeated or chronic stress leads to wear-and-tear on the body.
“allostatic load, a process through which an individual’s failure to adapt to conditions of repeated or chronic stress leads to wear-and tear on the body (McEwen, 2013; McEwen, 1998).”
Quote in the paperSubstantial claim0 of 2 sources checkedMay combine two claims.
PremisecitationExposure to physical abuse is related to exaggerated HPA-axis responses to acute psychosocial stress and to viewing violent films among young adolescents.
“Exposure to physical abuse is also related to exaggerated HPA-axis responses to acute psychosocial stress (Kuhlman et al., 2015) and to viewing violent films among young adolescents (Ivanov et al., 2011).”
Quote in the paperNot a substantial claim0 of 2 sources checked- cites Kuhlman et al., 2015
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- cites Ivanov et al., 2011 source
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Classified as probably not a substantial claim.
InterpretationreasoningEach element of adversity may differ in biological salience and therefore affect physiological systems differently.
“It is possible that each element of adversity (based on the degree of physical threat, caregiving disruption, and unpredictability) differs in biological salience and therefore affects the system differently.”
Quote in the paperSubstantial claimMay combine two claims.
InterpretationcitationLiving in an unpredictable environment as a child likely promotes upregulation of both diurnal cortisol and peripheral inflammatory markers.
“Living in an unpredictable environment as a child likely promotes upregulation of both diurnal cortisol and peripheral inflammatory markers.”
Quote in the paperSubstantial claim- Rests on an assumption: The frequency and magnitude of threat response system activation are reflected in cortisol and inflammatory markers.
May combine two claims.
PremisecitationTestosterone bound to androgen receptors can downregulate synthesis of proinflammatory cytokines and stimulate secretion of anti-inflammatory cytokines.
“When bound to androgen receptors, testosterone can downregulate synthesis of proinflammatory cytokines (D’Agostino et al., 1999; Li et al., 1993; Trigunaite et al., 2015), and stimulate secretion of anti-inflammatory cytokines (Liva and Voskuhl, 2001).”
Quote in the paperNot a substantial claim0 of 3 sources checkedMay combine two claims.
InterpretationreasoningDisrupted caregiving may be more related to poor down-regulation of glucocorticoids across contexts and low glucocorticoid sensitivity in immune cells and brain.
“Disrupted caregiving, in comparison, may be more related to poor down-regulation of glucocorticoids across many contexts and low glucocorticoid sensitivity in both immune cells and the brain.”
Quote in the paperSubstantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
InterpretationcitationThe inconsistency in newborn inflammatory responses may reflect differences in inflammatory sensitivity to different ligands or bacteria across the human lifespan.
“which may be an inconsistency that reflects differences in inflammatory sensitivity to different ligands or bacteria across the human lifespan (Levy et al., 2004; Mohamed et al., 2007).”
Quote in the paperNot a substantial claim0 of 2 sources checkedMay combine two claims.
PremisecitationSystemic inflammation induced during infancy results in impaired axonal growth and demyelination, decreased hippocampal neurogenesis, repetitive behaviors, and deficits in social memory during the juvenile period.
“In particular, systemic inflammation induced during infancy resulted in impaired axonal growth and demyelization, decreased hippocampal neurogenesis, repetitive behaviors, and deficits in social memory during the juvenile period (Lee et al., 2016).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Lee et al., 2016
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InterpretationcitationInflammatory processes in early life are distinct from those in adulthood and may continue to change into adolescence.
“Inflammatory processes in early life are distinct from those in adulthood, and may continue to exhibit change into adolescence.”
Quote in the paperSubstantial claimMay combine two claims.
InterpretationcitationDisrupted caregiving may impair coordination between glucocorticoids and immune cells, such as glucocorticoid insensitivity contributing to elevated circulating inflammation despite the presence of glucocorticoids.
“Disrupted caregiving may impair coordination between glucocorticoids and immune cells, such as glucocorticoid insensitivity in immune cells that may contribute to elevated circulating inflammation despite the presence of glucocorticoids (Cole, 2008; Cole et al., 2012).”
Quote in the paperSubstantial claim0 of 2 sources checkedMay combine two claims.
InterpretationreasoningInflammatory processes are immature during infancy, maturing throughout childhood, and interact with gonadal hormones during adolescence.
“In sum, inflammatory processes are immature during infancy, maturing throughout childhood, and interact with gonadal hormones during adolescence.”
Quote in the paperSubstantial claimMay combine two claims.
PremisecitationTotal early trauma exposure is associated with elevated C-reactive protein, driven by exposure to emotional abuse.
“Consistent with this, total early trauma exposure was associated with elevated CRP, which was driven by exposure to emotional abuse (Rooks et al., 2012).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Rooks et al., 2012 source
Not checked in the free run.
May combine two claims.
PremisecitationPBMC production of IL-12 in response to bacterial challenge increases with age, but stimulated production of IL-12 by 12 years of age is still substantially lower than in adults.
“In a study of infants, 5-year-olds, 12-year-olds, and adults, PBMC production of IL-12 in response to bacterial challenge was shown to increase with age; however, stimulated production of IL-12 by 12 years of age was still substantially lower than in adults (Upham et al., 2002).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Upham et al., 2002 source
Not checked in the free run.
Probably not a substantial claim: may not pass S4 (based).
InterpretationreasoningIn the context of elevated and poorly regulated glucocorticoids, observed heightened markers of inflammation may reflect glucocorticoid-insensitive immune cells.
“In the context of elevated and poorly-regulated glucocorticoids, the observed heightened markers of inflammation may reflect the presence of glucocorticoid insensitive immune cells.”
Quote in the paperNot a substantial claimClassified as probably not a substantial claim. May combine two claims.
InterpretationreasoningBased on the CVS model, youth exposed to unpredictable environments are expected to show chronic up-regulation of diurnal cortisol and elevated neuroinflammation that may indirectly increase peripheral inflammatory markers.
“Based upon this translational model, we expect youth exposed to an unpredictable environment to demonstrate chronic up-regulation of diurnal cortisol, and elevated neuroinflammation that may indirectly increase peripheral inflammatory markers.”
Quote in the paperSubstantial claimMay combine two claims.
PremisecitationChronic childhood stressors such as parent psychopathology, low socioeconomic status, and parent separation are prospectively associated with elevated inflammation when adolescent girls become depressed, and inflammatory markers remain elevated after symptoms recover.
“There is also an emerging body of evidence that more chronic childhood stressors such as parent psychopathology (e.g., MDD), low SES, and parent separation are prospectively associated with elevated inflammation when adolescent girls become depressed, and that inflammatory markers remain elevated even after symptoms recover (Miller and Cole, 2012).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Miller and Cole, 2012 source
Not checked in the free run.
May combine two claims.
InterpretationreasoningIt may be that adversity exposure during infancy leads to a hypersensitive HPA-axis whereas adversity exposure during adolescence may lead to hyposecretion of cortisol.
“It may be that adversity exposure during infancy leads to a hypersensitive HPA-axis whereas adversity exposure during adolescence may lead to hyposecretion of cortisol.”
Quote in the paperSubstantial claimProbably not a substantial claim: may not pass S3 (load-bearing), S4 (based).
Interpretationnone givenThere are some forms of childhood adversity that have no animal model analog.
“Further, there are some forms of childhood adversity that have no animal model analog.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S4 (based).
Interpretationnone givenExposure to adversity may have especially strong consequences during infancy and adolescence, periods when the HPA-axis and inflammatory processes undergo major changes.
“Exposure to adversity may be especially consequential during infancy and adolescence when major changes occur in the HPA-axis and inflammatory processes.”
Quote in the paperNot a substantial claimClassified as probably not a substantial claim.
InterpretationreasoningTiming of adversity exposure may contribute to the variation in the effects of adversity on HPA-axis and inflammatory processes.
“We also proposed that timing of adversity exposure may contribute to the variation in the effects of adversity on HPA-axis and inflammatory processes.”
Quote in the paperSubstantial claimMay combine two claims.
PremisecitationAdversity exposure during infancy is related to higher CRP at age 15 but not at age 10.
“Adversity exposure during infancy was related to higher CRP at age 15 but not at age 10, which raises the question of why adversity during infancy would be related to inflammation during mid-adolescence but not late childhood.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Slopen et al., 2013 source
Not checked in the free run.
Probably not a substantial claim: may not pass S4 (based).
Interpretationnone givenRepeated social defeat (RSD) may be a useful animal analog for understanding the physiological consequences of childhood adversity involving physical trauma and injury.
“We proposed that repeated social defeat (RSD) may be a useful animal analog for understanding the physiological consequences of childhood adversity involving physical trauma and injury, maternal separation may be useful for understanding disrupted caregiving environments, and chronic variable stress (CVS) may be useful for understanding the physiological consequences of living in an unpredictable”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
PremisecitationChildhood adversity accounts for approximately 1/3 of all psychiatric disorders and contributes significantly to chronic physical conditions.
“Childhood adversity accounts for approximately 1/3 of all psychiatric disorders (Kessler et al., 2010) and contributes significantly to chronic physical conditions (Scott et al., 2011).”
Quote in the paperNot a substantial claim0 of 2 sources checkedProbably not a substantial claim: may not pass S2 (checkable).
Interpretationnone givenChronic variable stress (CVS) may be useful for understanding the physiological consequences of living in an unpredictable developmental environment.
“We proposed that repeated social defeat (RSD) may be a useful animal analog for understanding the physiological consequences of childhood adversity involving physical trauma and injury, maternal separation may be useful for understanding disrupted caregiving environments, and chronic variable stress (CVS) may be useful for understanding the physiological consequences of living in an unpredictable”
Quote in the paperNot a substantial claimClassified as probably not a substantial claim.
PremisecitationThe brain and body may have a compensatory mechanism that downregulates cortisol secretion after an initial period of hypersecretion.
“Alternatively, the brain and body may have a compensatory mechanism that downregulates cortisol secretion after an initial period of hypersecretion (Heim et al., 2000; Miller et al., 2007).”
Quote in the paperSubstantial claim0 of 2 sources checkedClassified as probably not a substantial claim.
InterpretationreasoningThe inflammatory consequences of adversity during development may vary as a function of timing of adversity exposure.
“Nevertheless, there are studies hinting that the inflammatory consequences of adversity during development may vary as a function of timing of adversity exposure and these associations warrant further investigation.”
Quote in the paperSubstantial claimProbably not a substantial claim: may not pass S2 (checkable).
Interpretationnone givenMaternal separation may be useful for understanding disrupted caregiving environments.
“We proposed that repeated social defeat (RSD) may be a useful animal analog for understanding the physiological consequences of childhood adversity involving physical trauma and injury, maternal separation may be useful for understanding disrupted caregiving environments, and chronic variable stress (CVS) may be useful for understanding the physiological consequences of living in an unpredictable”
Quote in the paperNot a substantial claimMay combine two claims.
Interpretationnone givenAdversity during infancy may result in exaggerated cortisol early in life, which over time could lead to glucocorticoid receptor insensitivity.
“In particular, adversity during infancy may result in exaggerated cortisol early in life, which over time could lead to glucocorticoid receptor insensitivity.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing), S4 (based).
Interpretationnone givenTranslation of rodent models to humans is never direct.
“First, translation of rodent models to humans is never direct.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationThere is wealth of evidence establishing direct pathways between the SNS and physical health.
“There is also wealth of evidence establishing direct pathways between the SNS and physical health (Danese and McEwen, 2012; McLaughlin et al., 2014a; Seeman et al., 2001).”
Quote in the paperNot a substantial claim0 of 3 sources checkedMay combine two claims.
InterpretationreasoningBecause cortisol binding to glucocorticoid receptors on immune cells downregulates inflammation, glucocorticoid receptor insensitivity may contribute to heightened inflammation observed in relation to early adversity.
“Because binding of cortisol to glucocorticoid receptors on immune cells downregulate inflammation, glucocorticoid receptor insensitivity may also contribute to heightened inflammation that we observe in relation to early adversity.”
Quote in the paperSubstantial claimMay combine two claims.
PremisecitationEarly adversity during childhood and adolescence is related to greater expression of inflammatory-related genes and in vitro stimulation of inflammation, but not to circulating markers of inflammation in adolescents.
“Two studies have shown that early adversity during childhood and adolescence was related to greater expression of inflammatory-related genes and in vitro stimulation of inflammation, but not to circulating markers of inflammation in adolescents (Miller et al., 2009; Miller and Chen, 2010).”
Quote in the paperSubstantial claim0 of 2 sources checked- cites Miller et al., 2009
Not checked in the free run.
- cites Miller and Chen, 2010
Not checked in the free run.
May combine two claims.
InterpretationreasoningAdversity during adolescence may prime immune cells and potentially have persistent effects on inflammation.
“Given that adolescence is another period of significant biological and psychosocial development, adversity during adolescence may prime immune cells and potentially have persistent effects on inflammation.”
Quote in the paperSubstantial claimClassified as probably not a substantial claim.
Interpretationnone givenThe maternal separation/deprivation paradigm is particularly useful for understanding disruptions in the early caregiving environment.
“the maternal separation/deprivation paradigm for understanding disruptions in the early caregiving environment”
Quote in the paperSubstantial claim- Rests on an assumption: The maternal separation/deprivation paradigm is a valid model of disruptions in the early caregiving environment.
Probably not a substantial claim: may not pass S4 (based).
Interpretationnone givenThe RSD paradigm and its physiological effects are particularly useful for understanding physical trauma.
“we identify the RSD paradigm and its physiological consequences as particularly helpful for understanding physical trauma”
Quote in the paperNot a substantial claim- Rests on an assumption: The RSD paradigm is a valid model of physical trauma.
May combine two claims.
PremisecitationCandidate genetic risk factors have functional roles in serotonin transport, HPA-axis activation via CRH, glucocorticoid sensitivity, and BDNF production.
“Candidate genetic risk factors play functional roles in serotonin transport, activation of the HPA-axis via corticotropin releasing hormone (CRH), glucocorticoid sensitivity, and production of brain derived neurotrophic factors (BDNF).”
Quote in the paperNot a substantial claim0 of 2 sources checked
The paper relies on this without support.
Few studies have considered the role of timing in the association between childhood adversity and health.
“and few studies have considered the role of timing, thus limiting our understanding in the context of human development.”
The paper relies on this without support.
Well-characterized animal models of repeated social defeat, maternal separation, and chronic variable stress are valid analogs for the corresponding elements of human childhood adversity.
“we consider well-characterized animal models that may serve as useful analogs for these child adversity elements and provide informative causal models for understanding the distinct pathways from different types of developmental stress to disease.”
The paper relies on this without support.
Different types of childhood adversity commonly co-occur.
“In the face of co-occurrence of multiple adversities, which is more common than not, these effects may converge for multi-systemic vulnerability to disease across the lifespan.”
The paper relies on this without support.
Existing models have not directly examined whether physiological consequences vary across different types of adversity.
“Existing models have yet to directly examine whether physiological consequences vary across different types of adversity, limiting our understanding of the varying biological salience of different experiences during development.”
The paper relies on this without support.
No study has examined inflammatory responses to acute stress between physically abused and non-abused peers.
“however, no study to our knowledge has examined inflammatory responses to acute stress between physically abused and non-abused peers.”
The paper relies on this without support.
Information linking disrupted caregiving and inflammatory functioning is scarce.
“Information linking disrupted caregiving and inflammatory functioning is scarce, but still informative.”
The paper relies on this without support.
Elevated diurnal cortisol and inflammation serve as intermediate phenotypes linking childhood adversity to later disease.
“similar intermediate phenotype, elevated inflammation and atypical functioning of the HPA-axis.”
The paper relies on this without support.
The frequency and magnitude of threat response system activation are reflected in cortisol and inflammatory markers.
“elevated cortisol throughout the day and circulating inflammation are indicative of a threat sensitive system that activates frequently.”
The paper relies on this without support.
Innate immunity is the primary defense against infection in early life because adaptive immunity takes longer to develop.
“Innate immunity remains the primary defense against infection, as adaptive immunity takes much longer to develop.”
The paper relies on this without support.
Circulating immune cells, including macrophages, and lymphoid tissue cells express receptors for gonadal hormones.
“Circulating immune cells, including macrophages, and lymphoid tissue cells express receptors for gonadal hormones.”
The paper relies on this without support.
Youth exposed to sexual abuse rarely experience this abuse in the absence of other adversities.
“Unfortunately, youth exposed to sexual abuse rarely experience this abuse in the absence of other adversities.”
The paper relies on this without support.
The neurodevelopmental correlates of childhood sexual abuse are different from other types of abuse.
“Further exploration of the pathways outlined in this framework may further explain and contextualize observations that the neurodevelopmental correlates of childhood sexual abuse are different from other types of abuse.”
The paper relies on this without support.
Physical abuse of children is most commonly perpetrated by their parents or a known adult, while the RSD paradigm makes use of a new intruder each time.
“For example, physical abuse of children is most commonly perpetrated by their parents or a known adult, while the RSD paradigm makes use of a new intruder each time.”
The paper relies on this without support.
Animal models of adversity can elucidate HPA-axis and inflammatory pathways that are relevant to human childhood adversity and disease.
“The purpose of this review was to drive progress in the field by proposing that the challenges of characterizing the impact of childhood adversity on health may be addressed by drawing upon well-characterized animal models through which distinct HPA-axis and inflammatory pathways can be elucidated within a developmental framework.”
The paper relies on this without support.
The RSD paradigm is a valid model of physical trauma.
“we identify the RSD paradigm and its physiological consequences as particularly helpful for understanding physical trauma”
The paper relies on this without support.
The maternal separation/deprivation paradigm is a valid model of disruptions in the early caregiving environment.
“the maternal separation/deprivation paradigm for understanding disruptions in the early caregiving environment”
The paper relies on this without support.
The CVS paradigm is a valid model of growing up in an unpredictable environment.
“the CVS paradigm for understanding the physiological sequelae of growing up in an unpredictable environment”
The paper relies on this without support.
The predominant model in the field examines genetic vulnerability to disease in the context of cumulative life stress.
“the predominant model to date has been to examine genetic vulnerability to disease in the context of cumulative life stress”
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Puberty/adolescence represents the second particularly sensitive and vulnerable period with a new major change in HPA axis activity.
“The later developmental stage of puberty/adolescence represents the second particularly sensitive and vulnerable period with a new major change in HPA axis activity.”
From Developmental Trajectories of Early Life Stress and Trauma: A Narrative Review on Neurobiological Aspects Beyond Stress System Dysregulation (2019) · cites this paper as [101]
Section 3.2.1 says the HPA axis undergoes major change during adolescence and pubertal development, with increased sensitivity to the environment. Section 3.2.2 says puberty and adolescence may also be a sensitive period for enduring effects of adversity; it does not establish the claim’s more definite characterization of this as a particularly vulnerable period. (LLM, conf=0.83)
Experimental — accuracy not yet measuredInfancy and early childhood (age 0-5 years) represent one of the most vulnerable periods in brain development.
“Infancy and early childhood (age 0–5 y.o.a.) represent one of the most vulnerable periods in brain development (6, 101, 103, 104).”
From Developmental Trajectories of Early Life Stress and Trauma: A Narrative Review on Neurobiological Aspects Beyond Stress System Dysregulation (2019) · cites this paper as [101]
Section 3.2.1 says the central nervous system develops significantly during infancy and childhood and is vulnerable to glucocorticoids. But the paper does not identify ages 0–5 as a distinct period or establish that it is among the most vulnerable periods for brain development. In §4.2, it describes rapid neural development as extending from before birth through adolescence. Page numbers were unavailable in our copy. (LLM, conf=0.83)
Experimental — accuracy not yet measuredELS/CT during the first hypo-sensitive 2 years of life may lead to hyper-activity and hyper-responsiveness of the HPA axis, while ELS/CT during the hyper-active phase of adolescence may lead to a hypo-active and hypo-responsive HPA axis.
“Summarizing, ELS/CT during the first hypo-sensitive 2 years of life may lead to a hyper-activity and -responsiveness of HPA axis, while ELS/CT during the hyper-active phase of adolescence to a hypo-active and hypo-responsive HPA axis (101).”
From Developmental Trajectories of Early Life Stress and Trauma: A Narrative Review on Neurobiological Aspects Beyond Stress System Dysregulation (2019) · cites this paper as [101]
Section 3.2.2 (page not provided) links adversity in the first two years to elevated cortisol and reports lower baseline or blunted stress responses after recent adversity in youth aged 9–12. But section 3.2.1 says the HPA axis is responsive in the first months and becomes relatively hyporesponsive by about 12 months, rather than throughout the first two years. Section 3.2.2 also cautions that little is known about the effects of adolescent adversity independent of earlier exposure, so the proposed adolescent pattern is less established than the sentence implies. (LLM, conf=0.85)
Experimental — accuracy not yet measuredPositive ELS/CT history is an independent risk factor for peripheral immune dysregulation and long-term, low-grade inflammatory excess (a pro-inflammatory phenotype) in adulthood.
“There is growing evidence suggesting that positive ELS/CT history is an independent risk factor for peripheral immune dysregulation and long-term, low-grade inflammatory excess (i.e., a pro-inflammatory phenotype) in adulthood (101, 164–172).”
From Developmental Trajectories of Early Life Stress and Trauma: A Narrative Review on Neurobiological Aspects Beyond Stress System Dysregulation (2019) · cites this paper as [101]
Section 3.3.2 (page unavailable) suggests that early adversity may prime immune cells toward enduring inflammation, including in the periphery. But the paper treats the persistence of elevated circulating inflammation into adulthood as uncertain; section 2.2.2 also says physical and sexual abuse are not consistently linked to elevated adult inflammation after accounting for BMI and smoking. It therefore does not establish childhood adversity as an independent risk factor for a long-term adult pro-inflammatory phenotype. (LLM, conf=0.86)
Experimental — accuracy not yet measuredELS/CT exposure during the first hypo-sensitive 2 years of life may lead to a hyper-activity and -responsiveness of the HPA axis and accordingly higher risk for developing depression than PTSD.
“ELS/CT exposure during the first hypo-sensitive 2 years of life may lead to a hyper-activity and -responsiveness of HPA axis and accordingly higher risk for developing depression than PTSD, while”
From Developmental Trajectories of Early Life Stress and Trauma: A Narrative Review on Neurobiological Aspects Beyond Stress System Dysregulation (2019) · cites this paper as [101]
Section 3.2.2 (page unavailable) says adversity in infancy may heighten basal cortisol and stress responses, supporting the HPA-axis portion of the claim. It does not establish that this leads to a higher risk of depression than PTSD. Section 3.2.1 also describes hyporesponsivity as developing over the first year, rather than characterizing the entire first two years as hyporesponsive. (LLM, conf=0.88)
Experimental — accuracy not yet measured
Non-linear patterns in neurodevelopment lead to specific periods of greater stress system plasticity, which represent important vulnerability periods.
“Thereby, non-linear patterns in neurodevelopment lead to specific periods of greater stress system plasticity, which represent important vulnerability periods (96, 100, 101).”
From Developmental Trajectories of Early Life Stress and Trauma: A Narrative Review on Neurobiological Aspects Beyond Stress System Dysregulation (2019) · cites this paper as [101]
Section 3.2.2 describes possible periods of greater HPA-axis plasticity when adversity may have more lasting effects. Section 4.2 connects the timing of neural development to possible sensitive periods, but says these downstream effects need further study. The paper does not establish that non-linear neurodevelopment causes periods of greater stress-system plasticity; no page numbers were provided in our copy. (LLM, conf=0.83)
Experimental — accuracy not yet measuredELS/CT during the hyper-active phase of adolescence may lead to a hypo-active and hypo-responsive HPA axis and accordingly higher risk for developing PTSD than depression in adulthood.
“2 years of life may lead to a hyper-activity and -responsiveness of HPA axis and accordingly higher risk for developing depression than PTSD, while ELS/CT during the hyper-active phase of adolescence may lead to a hypo-active and hypo-responsive HPA axis and accordingly higher risk for developing PTSD than depression in adulthood (22, 101).”
From Developmental Trajectories of Early Life Stress and Trauma: A Narrative Review on Neurobiological Aspects Beyond Stress System Dysregulation (2019) · cites this paper as [101]
Section 3.2.1 (page unavailable) describes adolescence as a period of increased HPA-axis sensitivity. Section 3.2.2 (page unavailable) suggests that adolescent adversity may be associated with lower cortisol output and reports blunted stress responses in some youths. It does not establish lasting hypo-responsiveness in adulthood or a higher adult risk of PTSD than depression. (LLM, conf=0.86)
Experimental — accuracy not yet measuredPeriods of greater HPA axis plasticity may represent specific periods of greater vulnerability.
“Thereby, periods of greater HPA axis plasticity may represent specific periods of greater vulnerability (96, 100, 101), while mounting evidence suggests a differential impact of ELS/CT on HPA axis activity according to the specific developmental age of exposure (102).”
From Developmental Trajectories of Early Life Stress and Trauma: A Narrative Review on Neurobiological Aspects Beyond Stress System Dysregulation (2019) · cites this paper as [101]
Stress responsivity in early childhood decreases with age throughout the preschool period, suggesting a potential social buffering of the HPA axis by a nurturing caregiver, who may operate as a safety signal.
“Some longitudinal studies suggest that stress responsivity in early childhood decreases with age throughout the preschool period (101, 105–107), suggesting a potential social buffering of the HPA axis by a nurturing caregiver, who may operate as a safety signal (108–110).”
From Developmental Trajectories of Early Life Stress and Trauma: A Narrative Review on Neurobiological Aspects Beyond Stress System Dysregulation (2019) · cites this paper as [101]
After an initial hyper-responsive period, the HPA axis may later transition into a stress hypo-responsive period with lower basal cortisol levels and blunted stress-induced cortisol reactivity.
“After an initial hyper-responsive period, the HPA axis may later transition into a stress hypo-responsive period (SHRP) with lower basal cortisol levels and blunted stress-induced cortisol reactivity (101, 104–106).”
From Developmental Trajectories of Early Life Stress and Trauma: A Narrative Review on Neurobiological Aspects Beyond Stress System Dysregulation (2019) · cites this paper as [101]
In puberty/adolescence, the HPA axis transitions from hypo-responsivity into a period of increased activity with progressively higher basal and reactive cortisol levels.
“In this phase, the HPA axis transitions from hypo-responsivity into a period of increased activity (101, 114–116) with progressive higher basal (106, 110, 117, 118) and reactive (106, 118–121) cortisol levels.”
From Developmental Trajectories of Early Life Stress and Trauma: A Narrative Review on Neurobiological Aspects Beyond Stress System Dysregulation (2019) · cites this paper as [101]
ELS/CT together with higher cortisol during the stress hypo-responsive period could lead to glucocorticoid-receptor insensitivity through greater exposure to glucocorticoids over time, altering physiological HPA axis development.
“ELS/CT together with higher cortisol during this SHRP could possibly lead to GR insensitivity through greater exposure to GC over time, thus altering the physiological of HPA axis development (101, 112).”
From Developmental Trajectories of Early Life Stress and Trauma: A Narrative Review on Neurobiological Aspects Beyond Stress System Dysregulation (2019) · cites this paper as [101]
The dysfunctional neuroendocrine interface following ELS/CT may be closely correlated to immunological alterations and related long-term health consequences.
“Given this, the dysfunctional neuroendocrine interface following ELS/CT may be closely correlated to immunological alterations and related long-term health consequences (4, 36, 101, 153, 154, 172, 173)”
From Developmental Trajectories of Early Life Stress and Trauma: A Narrative Review on Neurobiological Aspects Beyond Stress System Dysregulation (2019) · cites this paper as [101]
Childhood trauma may lead to an increase in HPA axis sensitivity and a heightened response to subsequent stressors.
“childhood trauma may lead to an increase in HPA axis sensitivity and, thus, to a heightened response to subsequent stressors [28, 29].”
From The HPA Axis as Target for Depression (2024) · cites this paper as [29]
Early life stress is a potential risk factor for inflammation-related depression.
“Potential risk factors include early life stress (Danese et al., 2008; Kuhlman et al., 2017)”
From The role of inflammation in core features of depression: Insights from paradigms using exogenously-induced inflammation. (2018) · cites this paper as Kuhlman et al., 2017
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Childhood adversities and adult psychopathology in the WHO World Mental Health Surveys
Kessler, R. C., McLaughlin, K. A., Green, J. G., Gruber, M. J., Sampson, N. A., Zaslavsky, A. M., Aguilar-Gaxiola, S., Alhamzawi, A. O., Alonso, J., Angermeyer, M., et al. (2010) · British Journal of Psychiatry · doi:10.1192/bjp.bp.110.080499 · Cited by 2,640 · see citing works
The Hypothalamic–Pituitary–Adrenal Axis and Immune-Mediated Inflammation
Chrousos, G. P. (1995) · New England Journal of Medicine · doi:10.1056/nejm199505183322008 · Cited by 2,579 · see citing works
Clinical application of C-reactive protein for cardiovascular disease detection and prevention
Ridker, P. M. (2003) · Circulation · doi:10.1161/01.cir.0000053730.47739.3c · Cited by 2,513 · cited 1× · see citing works
“CRP, an acute phase protein synthesized in the liver in response to IL-6, can be a measure of chronic inflammation and concentrations greater than 3.0 mg/L are considered reliably predictive of cardiovascular disease risk (See Ridker, 2003 for review).”
InfluentialLearned helplessness: Theory and evidence
Maier, S. F., & Seligman, M. E. (1976) · Journal of Experimental Psychology: General · doi:10.1037/0096-3445.105.1.3 · Cited by 2,494 · cited 12× · see citing works
“Thus, we propose CVS as a plausible translational model for exposure to an unpredictable developmental environment.”
InfluentialMiller, G. E., Chen, E., & Zhou, E. S. (2007) · Psychological Bulletin · doi:10.1037/0033-2909.133.1.25 · Cited by 2,467 · see citing works
The p Factor: One General Psychopathology Factor in the Structure of Psychiatric Disorders?
Caspi, A., Houts, R. M., Belsky, D. W., Goldman-Mellor, S. J., Harrington, H., Israel, S., Meier, M. H., Ramrakha, S., Shalev, I., Poulton, R., et al. (2014) · Clinical Psychological Science · doi:10.1177/2167702613497473 · Cited by 2,449 · cited 1× · see citing works
“We know from several large epidemiological studies that childhood adversity predicts lifelong mental and physical illness in a dose-response manner (Caspi et al., 2014; Chapman et al., 2007; Kessler et al., 2010; Vachon et al., 2015).”
Adverse childhood experiences and the risk of depressive disorders in adulthood
Chapman, D. P., Whitfield, C. L., Felitti, V. J., Dube, S. R., Edwards, V. J., & Anda, R. F. (2004) · Journal of Affective Disorders · doi:10.1016/j.jad.2003.12.013 · Cited by 2,267 · see citing works
Adverse childhood experiences, allostasis, allostatic load and age-related disease
Danese, A., & McEwen, B. S. (2012) · Physiology & Behavior · doi:10.1016/j.physbeh.2011.08.019 · Cited by 2,140 · cited 1× · see citing works
“There is also wealth of evidence establishing direct pathways between the SNS and physical health (Danese and McEwen, 2012; McLaughlin et al., 2014a; Seeman et al., 2001).”
BOYCE, W. T., & ELLIS, B. J. (2005) · Development and Psychopathology · doi:10.1017/s0954579405050145 · Cited by 2,078 · see citing works
Cumulative risk and child development.
Evans, G. W., Li, D., & Whipple, S. S. (2013) · Psychological Bulletin · doi:10.1037/a0031808 · Cited by 2,024 · cited 1× · see citing works
“To date, the association between adversity and health has predominantly been tested as a dose-response relationship (e.g., Anda et al., 2006; Chapman et al., 2007; Evans et al., 2013; Kessler et al., 2010).”
The neurobiology of stress and development.
Gunnar, M., & Quevedo, K. (2007) · Annual Review of Psychology · doi:10.1146/annurev.psych.58.110405.085605 · Cited by 2,011 · cited 5× · see citing works
“A number of detailed reviews have previously described development of the HPA-axis (Gunnar and Quevedo, 2007; Gunnar and Donzella, 2002; Hostinar and Gunnar, 2013; Romeo, 2010), and thus, we highlight only major points of development.”
InfluentialThe complex role of estrogens in inflammation
Straub, R. H. (2007) · Endocrine Reviews · doi:10.1210/er.2007-0001 · Cited by 1,950 · see citing works
The role of the hypothalamic-pituitary-adrenal axis in neuroendocrine responses to stress
Smith, S. M., & Vale, W. W. (2006) · Dialogues in Clinical Neuroscience · doi:10.31887/dcns.2006.8.4/ssmith · Cited by 1,948 · see citing works
Evolution of the immune system in humans from infancy to old age
Simon, A. K., Hollander, G. A., & McMichael, A. (2015) · Proceedings of the Royal Society B: Biological Sciences · doi:10.1098/rspb.2014.3085 · Cited by 1,796 · see citing works
Miller, G. E., Chen, E., & Parker, K. J. (2011) · Psychological Bulletin · doi:10.1037/a0024768 · Cited by 1,785 · see citing works
The potential role of hypocortisolism in the pathophysiology of stress-related bodily disorders
Heim, C., Ehlert, U., & Hellhammer, D. H. (2000) · Psychoneuroendocrinology · doi:10.1016/s0306-4530(99)00035-9 · Cited by 1,688 · cited 2× · see citing works
“Alternatively, the brain and body may have a compensatory mechanism that downregulates cortisol secretion after an initial period of hypersecretion (Heim et al., 2000; Miller et al., 2007).”
Plotsky, P. M., & Meaney, M. J. (1993) · Molecular Brain Research · doi:10.1016/0169-328x(93)90189-v · Cited by 1,638 · cited 1× · see citing works
“Repeated and prolonged maternal separation in rodent pups results in exaggerated SNS and HPA-axis responses to stress during adolescence and adulthood (Kalinichev et al., 2002; Plotsky and Meaney, 1993).”
A standardized protocol for repeated social defeat stress in mice
Golden, S. A., Covington, H. E., Berton, O., & Russo, S. J. (2011) · Nature Protocols · doi:10.1038/nprot.2011.361 · Cited by 1,581 · cited 2× · see citing works
“And indeed, exposure to RSD leads to anxiety-like behavior in two-thirds of rodents (Golden et al., 2011), and the development of this behavioral phenotype is mediated by immune cell derived IL-6 (Hodes et al., 2014).”
Trajectories of brain development: point of vulnerability or window of opportunity?
Andersen, S. L. (2003) · Neuroscience & Biobehavioral Reviews · doi:10.1016/s0149-7634(03)00005-8 · Cited by 1,503 · see citing works
Immune modulation of learning, memory, neural plasticity and neurogenesis
Yirmiya, R., & Goshen, I. (2011) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2010.10.015 · Cited by 1,483 · cited 1× · see citing works
“Specifically, inflammatory cytokines play a role in early neural development (Stolp, 2013; Yirmiya and Goshen, 2011), and rodent studies indicate that elevated inflammatory cytokines can have persistent negative effects on brain and behavior.”
The neurobiological consequences of early stress and childhood maltreatment
Teicher, M. H., Andersen, S. L., Polcari, A., Anderson, C. M., Navalta, C. P., & Kim, D. M. (2003) · Neuroscience & Biobehavioral Reviews · doi:10.1016/s0149-7634(03)00007-1 · Cited by 1,465 · cited 1× · see citing works
“Each of these elements has been identified as salient to the development of the central nervous system with implications for learning and downstream physiological adaptations (Gunnar and Vazquez, 2006; McLaughlin et al., 2014b; Teicher et al., 2003).”
Chronic stress, glucocorticoid receptor resistance, inflammation, and disease risk
Cohen, S., Janicki-Deverts, D., Doyle, W. J., Miller, G. E., Frank, E., Rabin, B. S., & Turner, R. B. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1118355109 · Cited by 1,419 · see citing works
McLaughlin, K. A., Sheridan, M. A., & Lambert, H. K. (2014) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2014.10.012 · Cited by 1,389 · cited 3× · see citing works
“In line with our proposed framework, different types of stressors differentially impact neuroplasticity (Teicher & Samson, 2013), specifically in the limbic system (Cohen et al., 2013; Wilson et al., 2015), and specifically with regard to processing of threat and rewards (McLaughlin et al., 2014b).”
Allostatic load as a marker of cumulative biological risk: MacArthur studies of successful aging
Seeman, T. E., McEwen, B. S., Rowe, J. W., & Singer, B. H. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.081072698 · Cited by 1,385 · cited 1× · see citing works
“There is also wealth of evidence establishing direct pathways between the SNS and physical health (Danese and McEwen, 2012; McLaughlin et al., 2014a; Seeman et al., 2001).”
O'Connor, J. C., Lawson, M. A., André, C., Moreau, M., Lestage, J., Castanon, N., Kelley, K. W., & Dantzer, R. (2009) · Molecular Psychiatry · doi:10.1038/sj.mp.4002148 · Cited by 1,278 · see citing works
Steptoe, A., Hamer, M., & Chida, Y. (2007) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2007.03.011 · Cited by 1,278 · cited 1× · see citing works
“Notably, inflammation also increases in the context of psychosocial stress (Steptoe et al., 2007).”
Adolescent Development in Interpersonal and Societal Contexts
Smetana, J. G., Campione-Barr, N., & Metzger, A. (2006) · Annual Review of Psychology · doi:10.1146/annurev.psych.57.102904.190124 · Cited by 1,264 · cited 1× · see citing works
“That said, we know that family dynamics change over time (Tsai et al., 2005), especially from childhood to adolescence (Smetana et al., 2006).”
Childhood maltreatment predicts adult inflammation in a life-course study
Danese, A., Pariante, C. M., Caspi, A., Taylor, A., & Poulton, R. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0610362104 · Cited by 1,264 · cited 2× · see citing works
“Childhood adversity is associated with alterations to the body’s physiological stress response systems, including the hypothalamic-pituitary-adrenal axis (HPA-axis) (Gunnar and Quevedo, 2007; Heim and Nemeroff, 2001) and the inflammatory arm of the immune system (Carpenter et al., 2010; Danese et al., 2011; Danese et…”
Adolescence as a sensitive period of brain development
Fuhrmann, D., Knoll, L. J., & Blakemore, S.-J. (2015) · Trends in Cognitive Sciences · doi:10.1016/j.tics.2015.07.008 · Cited by 1,158 · cited 1× · see citing works
“However, adolescence is also a developmental phase characterized by increased sensitivity to the environment, operationalized by increased reactivity (Fuhrmann et al., 2015; e.g., Galván and McGlennen, 2013; Somerville et al., 2010).”
Kim-Cohen, J., Caspi, A., Taylor, A., Williams, B., Newcombe, R., Craig, I. W., & Moffitt, T. E. (2006) · Molecular Psychiatry · doi:10.1038/sj.mp.4001851 · Cited by 1,158 · see citing works
Avison, W. R., Brown, G. W., & Harris, T. (1990) · Contemporary Sociology A Journal of Reviews · doi:10.2307/2072630 · Cited by 1,148 · see citing works
Social regulation of the cortisol levels in early human development
Gunnar, M. R., & Donzella, B. (2002) · Psychoneuroendocrinology · doi:10.1016/s0306-4530(01)00045-2 · Cited by 1,088 · see citing works
Baumeister, D., Akhtar, R., Ciufolini, S., Pariante, C. M., & Mondelli, V (2016) · Molecular Psychiatry · doi:10.1038/mp.2015.67 · Cited by 1,084 · cited 1× · see citing works
“Although the association between early adversity exposure and inflammation has been welldocumented (See Baumeister et al., 2016; Miller et al., 2011 for review), the vast majority of studies have assessed early adversity exposure across multiple phases of child development, typically spanning…”
O'Mahony, S. M., Marchesi, J. R., Scully, P., Codling, C., Ceolho, A.-M., Quigley, E. M. M., Cryan, J. F., & Dinan, T. G. (2009) · Biological Psychiatry · doi:10.1016/j.biopsych.2008.06.026 · Cited by 1,069 · cited 1× · see citing works
“Similarly, rodent work focusing on the effects of early adversity on inflammatory markers has typically induced stress during postnatal days 2–20 (Figueiredo et al., 2016; O’Mahony et al., 2009; O’Malley et al., 2011; Roque et al., 2015).”
Teicher, M. H., & Samson, J. A. (2013) · American Journal of Psychiatry · doi:10.1176/appi.ajp.2013.12070957 · Cited by 1,050 · cited 1× · see citing works
“In line with our proposed framework, different types of stressors differentially impact neuroplasticity (Teicher & Samson, 2013), specifically in the limbic system (Cohen et al., 2013; Wilson et al., 2015), and specifically with regard to processing of threat and rewards (McLaughlin et al., 2014b).”
Somerville, L. H., Jones, R. M., & Casey, B. J. (2010) · Brain and Cognition · doi:10.1016/j.bandc.2009.07.003 · Cited by 1,025 · see citing works
Miller, G. E., Cohen, S., & Ritchey, A. K. (2002) · Health Psychology · doi:10.1037//0278-6133.21.6.531 · Cited by 977 · see citing works
Buckley, T. M., & Schatzberg, A. F. (2005) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2004-1056 · Cited by 964 · see citing works
Reciprocal regulation of the neural and innate immune systems
Irwin, M. R., & Cole, S. W. (2011) · Nature Reviews Immunology · doi:10.1038/nri3042 · Cited by 910 · cited 2× · see citing works
“When threat is perceived, the SNS releases noradrenaline, which promotes mobilization of stem cells from the bone marrow and activates immune gene transcription within white blood cells, organs, and tissues (Irwin and Cole, 2011).”
Brain corticosteroid receptor balance and homeostatic control
de Kloet, E. R. (1991) · Frontiers in Neuroendocrinology · Cited by 842 · see citing works
Miller, G. E., Chen, E., Fok, A. K., Walker, H., Lim, A., Nicholls, E. F., Cole, S., & Kobor, M. S. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0902971106 · Cited by 822 · cited 4× · see citing works
“Lower SES as indicated by parental occupation during a child’s first five years of life has also been associated with exaggerated inflammatory responses to pathogens (Miller et al., 2009a,b).”
InfluentialBiological Sensitivity to Context
Ellis, B. J., & Boyce, W. (2008) · Current Directions in Psychological Science · doi:10.1111/j.1467-8721.2008.00571.x · Cited by 797 · see citing works
Andersen, S. L., Tomada, A., Vincow, E. S., Valente, E., Polcari, A., & Teicher, M. H. (2008) · The Journal of Neuropsychiatry and Clinical Neurosciences · doi:10.1176/jnp.2008.20.3.292 · Cited by 788 · cited 1× · see citing works
“…emerging literature also suggests childhood trauma exposure during specific phases of development is important to later neurobiological functioning (Andersen et al., 2008; Cowell et al., 2015; Gee and Casey, 2015; Kuhlman et al., 2015a,b), and is critical to our understanding of how biological…”
Miller, G. E., Cohen, S., & Ritchey, A. K. (2002) · Health Psychology · doi:10.1037/0278-6133.21.6.531 · Cited by 769 · see citing works
Social regulation of gene expression in human leukocytes
Cole, S. W., Hawkley, L. C., Arevalo, J. M., Sung, C. Y., Rose, R. M., & Cacioppo, J. T. (2007) · Genome Biology · doi:10.1186/gb-2007-8-9-r189 · Cited by 745 · see citing works
Hostinar, C. E., Sullivan, R. M., & Gunnar, M. R. (2014) · Psychological Bulletin · doi:10.1037/a0032671 · Cited by 739 · cited 2× · see citing works
“Evidence supporting this notion already exists in maternal buffering of stress, suggesting that nurturing parenting can buffer the effect of other types of stress (Gunnar, 1998; Hagan et al., 2010; Hostinar et al., 2014).”
Behavioral Inhibition and Stress Reactivity: The Moderating Role of Attachment Security
Nachmias, M., Gunnar, M., Mangelsdorf, S., Parritz, R. H., & Buss, K. (1996) · Child Development · doi:10.2307/1131829 · Cited by 730 · see citing works
Behavioral Inhibition and Stress Reactivity: The Moderating Role of Attachment Security
Nachmias, M., Gunnar, M. R., Mangelsdorf, S. C., Parritz, R. H., & Buss, K. A. (1996) · Child Development · doi:10.1111/j.1467-8624.1996.tb01748.x · Cited by 724 · cited 1× · see citing works
“Likewise, studies of 12–18 month olds show that secure attachment is associated with attenuated cortisol responses to fear and physical pain (Ahnert et al., 2004; Gunnar et al., 1996b; Nachmias et al., 1996; Spangler, 1998).”
The cortisol awakening response - normal values and confounds.
Wüst, S., Wolf, J. M., Hellhammer, D. H., Federenko, I. S., Schommer, N. C., & Kirschbaum, C. (2000) · PubMed · Cited by 700 · see citing works
Essex, M. J., Klein, M. H., Cho, E., & Kalin, N. H. (2002) · Biological Psychiatry · doi:10.1016/s0006-3223(02)01553-6 · Cited by 698 · cited 1× · see citing works
“Maternal depression during early childhood robustly predicts elevated tonic cortisol during middle childhood (Ashman et al., 2002; Essex et al., 2002).”
Dimensions of early experience and neural development: deprivation and threat
Sheridan, M. A., & McLaughlin, K. A. (2014) · Trends in Cognitive Sciences · doi:10.1016/j.tics.2014.09.001 · Cited by 697 · cited 1× · see citing works
“Notably, the HPA-axis and inflammatory arm of the immune system respond and habituate differently to various types of stressors (Bowers et al., 2008; Kant et al., 1985; Kuhlman et al., 2014; Pacák, 1999; Pacák et al., 1998, 1995; Sheridan and McLaughlin, 2014; Weiner, 1992).”
Hodes, G. E., Pfau, M. L., Leboeuf, M., Golden, S. A., Christoffel, D. J., Bregman, D., Rebusi, N., Heshmati, M., Aleyasin, H., Warren, B. L., et al. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1415191111 · Cited by 692 · cited 10× · see citing works
“Some studies have found that LPS stimulation results in similar levels of TNF-α, IL-6, and IL-8 as in adults (Berner et al., 2002; Dembinski et al., 2002; Seghaye et al., 1998), which may be an inconsistency that reflects differences in inflammatory sensitivity to different ligands or bacteria across the human lifespa…”
InfluentialSelf-citationStress and the inflammatory response: A review of neurogenic inflammation
Black, P. H. (2002) · Brain Behavior and Immunity · doi:10.1016/s0889-1591(02)00021-1 · Cited by 687 · cited 2× · see citing works
“In response to infection or injury, various types of immune cells, including those in blood (e.g., monocytes, lymphocytes), tissue (e.g., macrophages), and in the brain (e.g., microglia) release pro-inflammatory cytokines (see Black, 2002; Miller et al., 2009a,b for review).”
Nusslock, R., & Miller, G. E. (2016) · Biological Psychiatry · doi:10.1016/j.biopsych.2015.05.017 · Cited by 672 · cited 1× · see citing works
“Indeed, distinct neural networks associated with psychopathology are more sensitive to cortisol and inflammation in children exposed to adversity (Nusslock and Miller, 2015), however these upstream processes are beyond the scope of the present review.”
Gunnar, M. R., Wewerka, S., Frenn, K., Long, J. D., & Griggs, C. (2009) · Development and Psychopathology · doi:10.1017/s0954579409000054 · Cited by 668 · cited 3× · see citing works
“Studies of youth have also found that cortisol responses to social stressors increase with age, and are associated with pubertal development (Blumenthal et al., 2014; Gunnar et al., 2009b; Stroud et al., 2009; Sumter et al., 2010; van den Bos et al., 2014).”
The cortisol awakening response: More than a measure of HPA axis function
Clow, A., Hucklebridge, F., Stalder, T., Evans, P., & Thorn, L. (2010) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2009.12.011 · Cited by 635 · see citing works
Stress response and the adolescent transition: performance versus peer rejection stressors
Stroud, L. R., Foster, E., Papandonatos, G. D., Handwerger, K., Granger, D. A., Kivlighan, K. T., & Niaura, R. (2009) · Development and Psychopathology · doi:10.1017/s0954579409000042 · Cited by 610 · see citing works
Creswell, J. D., Irwin, M. R., Burklund, L. J., Lieberman, M. D., Arevalo, J. M. G., Ma, J., Breen, E. C., & Cole, S. W. (2012) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2012.07.006 · Cited by 607 · cited 1× · see citing works
“For example, some behavioral interventions effectively reduce proinflammatory gene expression and not necessarily systemic markers (Bower et al., 2014, 2011; Creswell et al., 2012).”
Powell, N. D., Sloan, E. K., Bailey, M. T., Arevalo, J. M. G., Miller, G. E., Chen, E., Kobor, M. S., Reader, B. F., Sheridan, J. F., & Cole, S. W. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1310655110 · Cited by 588 · see citing works
Childhood Poverty and Health: Cumulative Risk Exposure and Stress Dysregulation
Evans, G. W., & Kim, P. (2007) · Psychological Science · doi:10.1111/j.1467-9280.2007.02008.x · Cited by 586 · see citing works
The immune system and developmental programming of brain and behavior
Bilbo, S. D., & Schwarz, J. M. (2012) · Frontiers in Neuroendocrinology · doi:10.1016/j.yfrne.2012.08.006 · Cited by 579 · see citing works
Gene×environment interactions at the serotonin transporter locus
Munafò, M. R., Durrant, C., Lewis, G., & Flint, J. (2009) · Biological Psychiatry · doi:10.1016/j.biopsych.2008.06.009 · Cited by 576 · see citing works
Gunnar, M. R., Talge, N. M., & Herrera, A. M. (2009) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2009.02.010 · Cited by 567 · see citing works
Prenatal stress and the programming of the HPA axis
Glover, V., O’Connor, T. G., & O’Donnell, K. (2010) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2009.11.008 · Cited by 567 · see citing works
Modern Approaches to Conceptualizing and Measuring Human Life Stress
Monroe, S. M. (2008) · Annual Review of Clinical Psychology · doi:10.1146/annurev.clinpsy.4.022007.141207 · Cited by 567 · see citing works
Obradović, J., Bush, N. R., Stamperdahl, J., Adler, N. E., & Boyce, W. T. (2010) · Child Development · doi:10.1111/j.1467-8624.2009.01394.x · Cited by 563 · see citing works
Suppressive effects of androgens on the immune system
Trigunaite, A., Dimo, J., & Jørgensen, T. N. (2015) · Cellular Immunology · doi:10.1016/j.cellimm.2015.02.004 · Cited by 551 · cited 1× · see citing works
“When bound to androgen receptors, testosterone can downregulate synthesis of proinflammatory cytokines (D’Agostino et al., 1999; Li et al., 1993; Trigunaite et al., 2015), and stimulate secretion of anti-inflammatory cytokines (Liva and Voskuhl, 2001).”
Psychometric properties of the Early Trauma Inventory-Self Report
Bremner, J. D., Bolus, R., & Mayer, E. A. (2007) · Journal of Nervous & Mental Disease · doi:10.1097/01.nmd.0000243824.84651.6c · Cited by 550 · cited 2× · see citing works
“…measures used to quantify childhood adversity exposure including the Childhood Trauma Questionnaire (Bernstein et al., 2003), Risky Families Questionnaire (Taylor et al., 2004), Early Trauma Inventory (Bremner et al., 2007), STRAIN (Slavich and Epel, 2010), and the LEDS (Brown and Harris, 1989).”
Neuroendocrinology and pathophysiology of the stress system
STRATAKIS, C. A., & CHROUSOS, G. P. (1995) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.1995.tb44666.x · Cited by 533 · cited 1× · see citing works
“When structures in the limbic system perceive a threat (e.g., pain, extreme temperatures, aggressor), the paraventricular nucleus (PVN) of the hypothalamus secretes corticotropin releasing hormone (CRH) and vasopressin (AVP) to the anterior pituitary gland (Stratakis and Chrousos, 1995).”
Ladd, C. O., Owens, M. J., & Nemeroff, C. B. (1996) · Endocrinology · doi:10.1210/endo.137.4.8625891 · Cited by 511 · cited 2× · see citing works
“Specifically, we highlight three paradigms: repeated social defeat (Avitsur et al., 2001; Reader et al., 2015), maternal separation (Ladd et al., 1996; Roque et al., 2014), and chronic variable stress (CVS) (Herman et al., 1995; Maier and Seligman, 1976; Simpkiss and Devine, 2003) (See Table 1).”
Immune modulation of the hypothalamic-pituitary-adrenal (HPA) axis during viral infection
Silverman, M. N., Pearce, B. D., Biron, C. A., & Miller, A. H. (2005) · Viral Immunology · doi:10.1089/vim.2005.18.41 · Cited by 506 · cited 1× · see citing works
“GRs can be found in immune cells and binding of glucocorticoids to the GRs downregulates cytokine production (Silverman et al., 2005).”
O’Connor, M.-F., Bower, J. E., Cho, H. J., Creswell, J. D., Dimitrov, S., Hamby, M. E., Hoyt, M. A., Martin, J. L., Robles, T. F., Sloan, E. K., et al. (2009) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2009.04.005 · Cited by 500 · see citing works
Self-citationTyrka, A. R., Price, L. H., Marsit, C., Walters, O. C., & Carpenter, L. L. (2012) · PLoS ONE · doi:10.1371/journal.pone.0030148 · Cited by 486 · cited 1× · see citing works
“Maternal care in infancy contributes to epigenetic regulation of the glucocorticoid receptor in the hippocampus (Anacker et al., 2014; McGowan et al., 2009) as well as in peripheral immune cells (Miller et al., 2011; Tyrka et al., 2012).”
Kalinichev, M., Easterling, K. W., Plotsky, P. M., & Holtzman, S. G. (2002) · Pharmacology Biochemistry and Behavior · doi:10.1016/s0091-3057(02)00781-5 · Cited by 484 · cited 1× · see citing works
“Repeated and prolonged maternal separation in rodent pups results in exaggerated SNS and HPA-axis responses to stress during adolescence and adulthood (Kalinichev et al., 2002; Plotsky and Meaney, 1993).”
Vachon, D. D., Krueger, R. F., Rogosch, F. A., & Cicchetti, D. (2015) · JAMA Psychiatry · doi:10.1001/jamapsychiatry.2015.1792 · Cited by 478 · cited 1× · see citing works
“We know from several large epidemiological studies that childhood adversity predicts lifelong mental and physical illness in a dose-response manner (Caspi et al., 2014; Chapman et al., 2007; Kessler et al., 2010; Vachon et al., 2015).”
Stress-induced prefrontal reorganization and executive dysfunction in rodents
Holmes, A., & Wellman, C. L. (2009) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2008.11.005 · Cited by 469 · see citing works
Association between plasma IL-6 response to acute stress and early-life adversity in healthy adults
Carpenter, L. L., Gawuga, C. E., Tyrka, A. R., Lee, J. K., Anderson, G. M., & Price, L. H. (2010) · Neuropsychopharmacology · doi:10.1038/npp.2010.159 · Cited by 464 · cited 2× · see citing works
“…stress response systems, including the hypothalamic-pituitary-adrenal axis (HPA-axis) (Gunnar and Quevedo, 2007; Heim and Nemeroff, 2001) and the inflammatory arm of the immune system (Carpenter et al., 2010; Danese et al., 2011; Danese et al., 2007; Slopen et al., 2013; Taylor et al., 2006).”
Herman, J. P., Adams, D. J., & Prewitt, C. M. (2008) · Neuroendocrinology · doi:10.1159/000126839 · Cited by 458 · cited 13× · see citing works
“Thus, we propose CVS as a plausible translational model for exposure to an unpredictable developmental environment.”
InfluentialHeim, C., Newport, D. J., Wagner, D., Wilcox, M. M., Miller, A. H., & Nemeroff, C. B. (2002) · Depression and Anxiety · doi:10.1002/da.10015 · Cited by 433 · cited 1× · see citing works
“Adaptive diurnal functioning of the HPA-axis has implications for other physiological processes such as immune functioning (Heim et al., 2002; Watts-English et al., 2006), growth (Kertes et al., 2008), sleep (Buckley and Schatzberg, 2005) and therefore dysregulation may be related to disruptions in…”
McLaughlin, K. A., Sheridan, M. A., Tibu, F., Fox, N. A., Zeanah, C. H., & Nelson, C. A. (2015) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1423363112 · Cited by 426 · cited 1× · see citing works
“The only true experiment to date (McLaughlin et al., 2015) supports the idea of a sensitive period during the first two years of life.”
Childhood maltreatment and inflammatory markers: a systematic review.
Coelho, R., Viola, T. W., Walss‐Bass, C., Brietzke, E., & Grassi‐Oliveira, R. (2014) · Acta Psychiatrica Scandinavica · doi:10.1111/acps.12217 · Cited by 426 · cited 1× · see citing works
“Overall, experiencing multiple types of maltreatment before adulthood was associated with elevated CRP, fibrinogen, and proinflammatory cytokines (Coelho et al., 2014).”
Teicher, M. H., & Parigger, A. (2015) · PLOS ONE · doi:10.1371/journal.pone.0117423 · Cited by 421 · cited 1× · see citing works
“In fact, the Maltreatment and Abuse Chronology of Exposure (MACE) (Teicher and Parigger, 2015) is among the first measures to directly assess timing of childhood maltreatment exposure within a developmental framework.”
Miller, G. E., & Chen, E. (2010) · Psychological Science · doi:10.1177/0956797610370161 · Cited by 413 · see citing works
Testosterone Acts Directly on CD4+ T Lymphocytes to Increase IL-10 Production
Liva, S. M., & Voskuhl, R. R. (2001) · The Journal of Immunology · doi:10.4049/jimmunol.167.4.2060 · Cited by 395 · cited 2× · see citing works
“When bound to androgen receptors, testosterone can downregulate synthesis of proinflammatory cytokines (D’Agostino et al., 1999; Li et al., 1993; Trigunaite et al., 2015), and stimulate secretion of anti-inflammatory cytokines (Liva and Voskuhl, 2001).”
Psychoneuroimmunology of early-life stress: the hidden wounds of childhood trauma?
Danese, A., & J Lewis, S. (2017) · Neuropsychopharmacology · doi:10.1038/npp.2016.198 · Cited by 393 · see citing works
Early Environment, Emotions, Responses to Stress, and Health
Taylor, S. E., Lerner, J. S., Sage, R. M., Lehman, B. J., & Seeman, T. E. (2004) · Journal of Personality · doi:10.1111/j.1467-6494.2004.00300.x · Cited by 390 · see citing works
ELLIS, B. J., ESSEX, M. J., & BOYCE, W. T. (2005) · Development and Psychopathology · doi:10.1017/s0954579405050157 · Cited by 383 · see citing works
Levy, O., Zarember, K. A., Roy, R. M., Cywes, C., Godowski, P. J., & Wessels, M. R. (2004) · The Journal of Immunology · doi:10.4049/jimmunol.173.7.4627 · Cited by 375 · see citing works
Scott, K. M. (2011) · Archives of General Psychiatry · doi:10.1001/archgenpsychiatry.2011.77 · Cited by 361 · cited 2× · see citing works
“, 2010) and contributes significantly to chronic physical conditions (Scott et al., 2011).”
Development of human brain cortical network architecture during infancy
Gao, W., Alcauter, S., Smith, J. K., Gilmore, J. H., & Lin, W. (2015) · Brain Structure and Function · doi:10.1007/s00429-014-0710-3 · Cited by 356 · cited 1× · see citing works
“For instance, the central nervous system undergoes significant development during infancy and childhood (Andersen, 2003; Gao et al., 2015; Huang et al., 2015; Qiu et al., 2015) and is vulnerable to the effects of glucocorticoids (Gunnar, 1998; Lupien et al., 2009).”
Low Cortisol and Risk for PTSD in Adult Offspring of Holocaust Survivors
Yehuda, R., Bierer, L. M., Schmeidler, J., Aferiat, D. H., Breslau, I., & Dolan, S. (2000) · American Journal of Psychiatry · doi:10.1176/appi.ajp.157.8.1252 · Cited by 353 · cited 2× · see citing works
“, 2008), and adult offspring of Holocaust survivors reporting more exposure to emotional abuse and neglect exhibit elevated urinary cortisol (Yehuda et al., 2000).”
Tyrka, A. R., Price, L. H., Kao, H.-T., Porton, B., Marsella, S. A., & Carpenter, L. L. (2010) · Biological Psychiatry · doi:10.1016/j.biopsych.2009.08.014 · Cited by 342 · cited 1× · see citing works
“Indeed, childhood abuse significantly accelerates biological aging (Tyrka et al., 2010) and all-cause mortality (Chen et al., 2016).”
Ahnert, L., Gunnar, M. R., Lamb, M. E., & Barthel, M. (2004) · Child Development · doi:10.1111/j.1467-8624.2004.00698.x · Cited by 334 · see citing works
Clustering of depression and inflammation in adolescents previously exposed to childhood adversity
Miller, G. E., & Cole, S. W. (2012) · Biological Psychiatry · doi:10.1016/j.biopsych.2012.02.034 · Cited by 331 · cited 2× · see citing works
“…chronic childhood stressors such as parent psychopathology (e.g., MDD), low SES, and parent separation are prospectively associated with elevated inflammation when adolescent girls become depressed, and that inflammatory markers remain elevated even after symptoms recover (Miller and Cole, 2012).”
Childhood adversity and inflammatory processes in youth: a prospective study
Slopen, N., Kubzansky, L. D., McLaughlin, K. A., & Koenen, K. C. (2013) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2012.05.013 · Cited by 330 · cited 3× · see citing works
“Slopen et al. (2013) also found that adversity during middle childhood (6–8 years) was related to higher CRP at both 10 and 15 years.”
Adolescence: A central event in shaping stress reactivity
Romeo, R. D. (2010) · Developmental Psychobiology · doi:10.1002/dev.20437 · Cited by 325 · cited 1× · see citing works
“A number of detailed reviews have previously described development of the HPA-axis (Gunnar and Quevedo, 2007; Gunnar and Donzella, 2002; Hostinar and Gunnar, 2013; Romeo, 2010), and thus, we highlight only major points of development.”
Social stress induces glucocorticoid resistance in subordinate animals
Avitsur, R., Stark, J. L., & Sheridan, J. F. (2001) · Hormones and Behavior · doi:10.1006/hbeh.2001.1653 · Cited by 321 · cited 3× · see citing works
“…attack by the aggressor (Merlot et al., 2003) exhibit glucocorticoid resistant immune cells, systemic increases in glucocorticoids, exaggerated inflammatory responses (Avitsur et al., 2001; Stark et al., 2001), and increases in pro-inflammatory gene expression in immune cells (Powell et al., 2013).”
Kiess, W., Meidert, A. S., Dressendörfer, R. A., Schriever, K., Kessler, U., Köunig, A., Hp, S., & Strasburger, C. J. (1995) · Pediatric Research · doi:10.1203/00006450-199504000-00020 · Cited by 319 · cited 1× · see citing works
“In a sample of almost 400 youth aged 7–15 years, for example, diurnal cortisol was found to positively correlate with pubertal stage (Kiess et al., 1995).”
Stress hormone levels of children of depressed mothers
ASHMAN, S. B., DAWSON, G., PANAGIOTIDES, H., YAMADA, E., & WILKINSON, C. W. (2002) · Development and Psychopathology · doi:10.1017/s0954579402002080 · Cited by 310 · cited 2× · see citing works
“In support of this notion, a study of 7–8 year old children showed that a lifetime history of maternal depression was associated with elevated cortisol; notably, maternal depression during the child’s first two years of life was the best predictor of elevated cortisol (Ashman et al., 2002).”
Childhood maltreatment and its effect on neurocognitive functioning: timing and chronicity matter
Cowell, R. A., Cicchetti, D., Rogosch, F. A., & Toth, S. L. (2015) · Development and Psychopathology · doi:10.1017/s0954579415000139 · Cited by 307 · cited 1× · see citing works
“…suggests childhood trauma exposure during specific phases of development is important to later neurobiological functioning (Andersen et al., 2008; Cowell et al., 2015; Gee and Casey, 2015; Kuhlman et al., 2015a,b), and is critical to our understanding of how biological systems develop under…”
Early-life stress has persistent effects on amygdala function and development in mice and humans
Malter Cohen, M., Jing, D., Yang, R. R., Tottenham, N., Lee, F. S., & Casey, B. J. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1310163110 · Cited by 307 · see citing works
Biological embedding of stress through inflammation processes in childhood
Danese, A., Caspi, A., Williams, B., Ambler, A., Sugden, K., Mika, J., Werts, H., Freeman, J., Pariante, C. M., Moffitt, T. E., et al. (2011) · Molecular Psychiatry · doi:10.1038/mp.2010.5 · Cited by 301 · see citing works
Adam, E. K. (2001) · Psychoneuroendocrinology · doi:10.1016/s0306-4530(00)00045-7 · Cited by 300 · see citing works
Social vocalizations can release oxytocin in humans
Seltzer, L. J., Ziegler, T. E., & Pollak, S. D. (2010) · Proceedings of the Royal Society B: Biological Sciences · doi:10.1098/rspb.2010.0567 · Cited by 298 · see citing works
Physical abuse amplifies attention to threat and increases anxiety in children.
Shackman, J. E., Shackman, A. J., & Pollak, S. D. (2007) · Emotion · doi:10.1037/1528-3542.7.4.838 · Cited by 297 · cited 2× · see citing works
“Consistent with these animal models, both children (Shackman et al., 2007) and adults (Stein et al., 1996) exposed to physical abuse demonstrate increased risk for anxiety disorders and a wide range of physical and behavioral distress.”
Taylor, S. E., Lehman, B. J., Kiefe, C. I., & Seeman, T. E. (2006) · Biological Psychiatry · doi:10.1016/j.biopsych.2006.03.016 · Cited by 296 · see citing works
Social stress induces glucocorticoid resistance in macrophages
Stark, J. L., Avitsur, R., Padgett, D. A., Campbell, K. A., Beck, F. M., & Sheridan, J. F. (2001) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.2001.280.6.r1799 · Cited by 295 · see citing works
Gunnar, M. R. (1998) · Preventive Medicine · doi:10.1006/pmed.1998.0276 · Cited by 295 · cited 2× · see citing works
“For instance, the central nervous system undergoes significant development during infancy and childhood (Andersen, 2003; Gao et al., 2015; Huang et al., 2015; Qiu et al., 2015) and is vulnerable to the effects of glucocorticoids (Gunnar, 1998; Lupien et al., 2009).”
Pacák, K., Palkovits, M., Yadid, G., Květňanský, R., Kopin, I. J., & Goldstein, D. S. (1998) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.1998.275.4.r1247 · Cited by 292 · cited 1× · see citing works
“Notably, the HPA-axis and inflammatory arm of the immune system respond and habituate differently to various types of stressors (Bowers et al., 2008; Kant et al., 1985; Kuhlman et al., 2014; Pacák, 1999; Pacák et al., 1998, 1995; Sheridan and McLaughlin, 2014; Weiner, 1992).”
Grønli, J., Murison, R. C. C., Fiske, E., Bjorvatn, B., Sørensen, E., Portas, C. M., & URSIN, R. (2005) · Physiology & Behavior · doi:10.1016/j.physbeh.2005.02.007 · Cited by 292 · cited 1× · see citing works
“CVS also causes elevated markers of inflammation including IL-6, IL-1ß, and TNF-α in the hippocampus (Tagliari et al., 2010), but not always in the periphery (Grønli et al., 2005).”
Stress Neurobiology and Developmental Psychopathology
Gunnar, M. R., & Vázquez, D. M. (2015) · Wiley eBooks · doi:10.1002/9780470939390.ch13 · Cited by 291 · see citing works
Childhood bullying involvement predicts low-grade systemic inflammation into adulthood
Copeland, W. E., Wolke, D., Lereya, S. T., Shanahan, L., Worthman, C., & Costello, E. J. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1323641111 · Cited by 291 · see citing works
Sleep loss activates cellular markers of inflammation: Sex differences
Irwin, M. R., Carrillo, C., & Olmstead, R. (2010) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2009.06.001 · Cited by 287 · cited 1× · see citing works
“Functions of white blood cells can also be measured in vitro by measuring the production of cytokines following exposure to either a bacterial or anti-inflammatory stimulus (Irwin et al., 2010; Miller et al., 2009a,b).”
Perturbing the organism: the biology of stressful experience
(1993) · Choice Reviews Online · doi:10.5860/choice.30-2669 · Cited by 285 · see citing works
Childhood physical and sexual abuse in patients with anxiety disorders and in a community sample
(1996) · American Journal of Psychiatry · doi:10.1176/ajp.153.2.275 · Cited by 284 · see citing works
Bower, J. E., Greendale, G., Crosswell, A. D., Garet, D., Sternlieb, B., Ganz, P. A., Irwin, M. R., Olmstead, R., Arevalo, J., & Cole, S. W. (2014) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2014.01.019 · Cited by 283 · see citing works
Self-citationGene–environment interactions: early life stress and risk for depressive and anxiety disorders
Nugent, N. R., Tyrka, A. R., Carpenter, L. L., & Price, L. H. (2011) · Psychopharmacology · doi:10.1007/s00213-010-2151-x · Cited by 269 · cited 1× · see citing works
“This literature has been thoroughly and carefully reviewed and goes beyond the scope of this review (See for example Nugent et al., 2011; Tyrka et al., 2013).”
Tyrka, A. R., Price, L. H., Gelernter, J., Schepker, C., Anderson, G. M., & Carpenter, L. L. (2009) · Biological Psychiatry · doi:10.1016/j.biopsych.2009.05.012 · Cited by 264 · cited 1× · see citing works
“…to examine genetic vulnerability to disease in the context of cumulative life stress even though it is more likely that individuals carry genetic vulnerability to specific intermediate phenotypes within a complex system when exposed to relevant life stressors (See for example Tyrka et al., 2009).”
Spangler, G., & Schieche, M. (1998) · International Journal of Behavioral Development · doi:10.1080/016502598384126 · Cited by 262 · cited 1× · see citing works
“Likewise, studies of 12–18 month olds show that secure attachment is associated with attenuated cortisol responses to fear and physical pain (Ahnert et al., 2004; Gunnar et al., 1996b; Nachmias et al., 1996; Spangler, 1998).”
Sex Hormones Modulate Inflammatory Mediators Produced by Macrophages <sup>a</sup>
D'AGOSTINO, P., MILANO, S., BARBERA, C., DI BELLA, G., LA ROSA, M., FERLAZZO, V., FARRUGGIO, R., MICELI, D. M., MIELE, M., CASTAGNETTA, L., et al. (1999) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.1999.tb07667.x · Cited by 262 · see citing works
Development of interleukin-12-producing capacity throughout childhood
Upham, J. W., Lee, P. T., Holt, B. J., Heaton, T., Prescott, S. L., Sharp, M. J., Sly, P. D., & Holt, P. G. (2002) · Infection and Immunity · doi:10.1128/iai.70.12.6583-6588.2002 · Cited by 257 · cited 1× · see citing works
“In a study of infants, 5-year-olds, 12-yearolds, and adults, PBMC production of IL-12 in response to bacterial challenge was shown to increase with age; however, stimulated production of IL-12 by 12 years of age was still substantially lower than in adults (Upham et al., 2002).”
Wright, R. J., Finn, P., Contreras, J. P., Cohen, S., Wright, R. O., Staudenmayer, J., Wand, M., Perkins, D., Weiss, S. T., & Gold, D. R. (2004) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2004.03.032 · Cited by 256 · cited 1× · see citing works
“For instance, 2-year-old children whose parents reported higher cumulative stress during the child’s life exhibited heightened TNF-α responses to an allergen (Wright et al., 2004).”
Childhood parental loss and adult hypothalamic-pituitary-adrenal function
Tyrka, A. R., Wier, L., Price, L. H., Ross, N., Anderson, G. M., Wilkinson, C. W., & Carpenter, L. L. (2008) · Biological Psychiatry · doi:10.1016/j.biopsych.2008.01.011 · Cited by 250 · cited 1× · see citing works
“Adult men who experienced the loss of a parent via death or desertion during childhood exhibit larger responses to the Dex/CHR test (Tyrka et al., 2008), and adult offspring of Holocaust survivors reporting more exposure to emotional abuse and neglect exhibit elevated urinary cortisol (Yehuda et…”
The impact of developmental timing for stress and recovery
Gee, D. G., & Casey, B. J. (2015) · Neurobiology of Stress · doi:10.1016/j.ynstr.2015.02.001 · Cited by 245 · cited 2× · see citing works
“…during specific phases of development is important to later neurobiological functioning (Andersen et al., 2008; Cowell et al., 2015; Gee and Casey, 2015; Kuhlman et al., 2015a,b), and is critical to our understanding of how biological systems develop under conditions of threat and…”
Allostasis and allostatic load in the context of poverty in early childhood
Blair, C., Raver, C. C., Granger, D. A., Mills-Koonce, R., Hibel, L. C., & The Family Life Project Key Investigators (2011) · Development and Psychopathology · doi:10.1017/s0954579411000344 · Cited by 240 · see citing works
Diffusion tensor imaging for understanding brain development in early life
Qiu, A., Mori, S., & Miller, M. I. (2015) · Annual Review of Psychology · doi:10.1146/annurev-psych-010814-015340 · Cited by 238 · see citing works
Early life adversity and the epigenetic programming of hypothalamic-pituitary-adrenal function
Anacker, C., O'Donnell, K. J., & Meaney, M. J. (2014) · Dialogues in Clinical Neuroscience · doi:10.31887/dcns.2014.16.3/canacker · Cited by 237 · cited 3× · see citing works
“Maternal care in infancy contributes to epigenetic regulation of the glucocorticoid receptor in the hippocampus (Anacker et al., 2014; McGowan et al., 2009) as well as in peripheral immune cells (Miller et al.”
The Brain on Stress: Toward an Integrative Approach to Brain, Body, and Behavior
McEwen, B. S. (2013) · Perspectives on Psychological Science · doi:10.1177/1745691613506907 · Cited by 237 · cited 2× · see citing works
“…overlapping theories have been developed to provide a framework for how childhood adversity confers risk for illness through allostatic load, a process through which an individual’s failure to adapt to conditions of repeated or chronic stress leads to wear-and tear on the body (McEwen, 2013, 1998).”
Tiwari-Woodruff, S., Morales, L. B. J., Lee, R., & Voskuhl, R. R. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0703783104 · Cited by 234 · see citing works
Salivary cortisol and dehydroepiandrosterone in relation to puberty and gender
Netherton, C. M., Goodyer, I. M., Tamplin, A., & Herbert, J. (2003) · Psychoneuroendocrinology · doi:10.1016/s0306-4530(02)00150-6 · Cited by 231 · cited 2× · see citing works
“Unlike the relatively low basal and stress-induced cortisol responses during childhood, basal cortisol increases from childhood to adolescence and is positively associated with pubertal development (Gunnar et al., 2009b; Gunnar and Vazquez, 2006; Hostinar et al., 2015; Legro, 2003; Netherton et al., 2004; Stroud et al…”
Multifactorial regulation of the hypothalamic-pituitary-adrenal axis during development
Rosenfeld, P., Suchecki, D., & Levine, S. D. (1992) · Neuroscience & Biobehavioral Reviews · doi:10.1016/s0149-7634(05)80196-4 · Cited by 230 · cited 1× · see citing works
“Rodent research indicates that the neonatal period is marked by a stress hyporesponsive period (SHRP), in which neonates exhibit blunted basal and stress-induced corticosterone (Gunnar and Quevedo, 2007; Rosenfeld et al., 1992).”
Shirtcliff, E. A., Allison, A. L., Armstrong, J. M., Slattery, M. J., Kalin, N. H., & Essex, M. J. (2011) · Developmental Psychobiology · doi:10.1002/dev.20607 · Cited by 230 · see citing works
Gunnar, M. R., Larson, M. C., Hertsgaard, L. A., Harris, M. L., & Brodersen, L. (1992) · Child Development · doi:10.1111/j.1467-8624.1992.tb01627.x · Cited by 229 · cited 1× · see citing works
“Supporting this notion, one study found that a responsive caregiver during maternal separation attenuated cortisol responses among 9 month olds (Gunnar et al., 1992).”
Habituation to repeated stress is stressor specific
Jean Kant, G., Eggleston, T., Landman-Roberts, L., Kenion, C. C., Driver, G. C., & Meyerhoff, J. L. (1985) · Pharmacology Biochemistry and Behavior · doi:10.1016/0091-3057(85)90286-2 · Cited by 225 · cited 1× · see citing works
“Notably, the HPA-axis and inflammatory arm of the immune system respond and habituate differently to various types of stressors (Bowers et al., 2008; Kant et al., 1985; Kuhlman et al., 2014; Pacák, 1999; Pacák et al., 1998, 1995; Sheridan and McLaughlin, 2014; Weiner, 1992).”
Development of Human Brain Structural Networks Through Infancy and Childhood
Huang, H., Shu, N., Mishra, V., Jeon, T., Chalak, L., Wang, Z. J., Rollins, N., Gong, G., Cheng, H., Peng, Y., et al. (2015) · Cerebral Cortex · doi:10.1093/cercor/bht335 · Cited by 223 · see citing works
Stressor-specific alterations in corticosterone and immune responses in mice
Bowers, S. L., Bilbo, S. D., Dhabhar, F. S., & Nelson, R. J. (2008) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2007.07.012 · Cited by 222 · cited 1× · see citing works
“Notably, the HPA-axis and inflammatory arm of the immune system respond and habituate differently to various types of stressors (Bowers et al., 2008; Kant et al., 1985; Kuhlman et al., 2014; Pacák, 1999; Pacák et al., 1998, 1995; Sheridan and McLaughlin, 2014; Weiner, 1992).”
Dampening of Adrenocortical Responses during Infancy: Normative Changes and Individual Differences
Gunnar, M. R., Brodersen, L., Krueger, K., & Rigatuso, J. (1996) · Child Development · doi:10.1111/j.1467-8624.1996.tb01770.x · Cited by 222 · cited 2× · see citing works
“Likewise, studies of 12–18 month olds show that secure attachment is associated with attenuated cortisol responses to fear and physical pain (Ahnert et al., 2004; Gunnar et al., 1996b; Nachmias et al., 1996; Spangler, 1998).”
Pereira, J., Vickers, K., Atkinson, L., Gonzalez, A., Wekerle, C., & Levitan, R. (2012) · Child Abuse & Neglect · doi:10.1016/j.chiabu.2012.01.006 · Cited by 222 · see citing works
The Psychobiology of Maltreatment in Childhood
Watts‐English, T., Fortson, B. L., Gibler, N., Hooper, S. R., & Bellis, M. D. D. (2006) · Journal of Social Issues · doi:10.1111/j.1540-4560.2006.00484.x · Cited by 218 · cited 2× · see citing works
“Adaptive diurnal functioning of the HPA-axis has implications for other physiological processes such as immune functioning (Heim et al., 2002; Watts-English et al., 2006), growth (Kertes et al., 2008), sleep (Buckley and Schatzberg, 2005) and therefore dysregulation may be related to disruptions in…”
Salivary alpha amylase-cortisol asymmetry in maltreated youth
Gordis, E. B., Granger, D. A., Susman, E. J., & Trickett, P. K. (2008) · Hormones and Behavior · doi:10.1016/j.yhbeh.2007.09.002 · Cited by 211 · cited 1× · see citing works
“Maltreated youth demonstrate less symmetry between sympathetic and HPA-axis responses to acute stress than non-maltreated youth (Gordis et al., 2008).”
Transcriptional modulation of the developing immune system by early life social adversity
Cole, S. W., Conti, G., Arevalo, J. M. G., Ruggiero, A. M., Heckman, J. J., & Suomi, S. J. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1218253109 · Cited by 207 · see citing works
The hormonal costs of subtle forms of infant maltreatment
Bugental, D. B., Martorell, G. A., & Barraza, V. (2003) · Hormones and Behavior · doi:10.1016/s0018-506x(02)00008-9 · Cited by 204 · cited 3× · see citing works
“Infants (Bugental et al., 2003) and school-aged children (Kuhlman et al., 2014) exposed to frequent physical punishment demonstrate exaggerated cortisol responses to psychological stress.”
InfluentialDickerson, S. S., Gable, S. L., Irwin, M. R., Aziz, N., & Kemeny, M. E. (2009) · Psychological Science · doi:10.1111/j.1467-9280.2009.02437.x · Cited by 197 · cited 1× · see citing works
“…line of experimental research has demonstrated that different types of stress vary in their salience to the key biological systems thought to mediate stress and negative health outcomes (e.g., Dickerson et al., 2009; Dickerson and Kemeny, 2004; Kuhlman et al., 2014; Lopez-Duran et al., 2009a).”
Neuroendocrine dysregulation following early social deprivation in children
Fries, A. B. W., Shirtcliff, E. A., & Pollak, S. D. (2008) · Developmental Psychobiology · doi:10.1002/dev.20319 · Cited by 192 · see citing works
Roque, A., Ochoa‐Zarzosa, A., & Torner, L. (2015) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2015.09.017 · Cited by 190 · see citing works
A family-oriented psychosocial intervention reduces inflammation in low-SES African American youth
Miller, G. E., Brody, G. H., Yu, T., & Chen, E. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1406578111 · Cited by 180 · cited 1× · see citing works
“An intervention study also showed that relative to a waitlist control, a 7-week family-oriented psychosocial intervention implemented among low-SES, 11-year-old youth resulted in lower markers of inflammation when youth were 19- years-old (Miller et al., 2014).”
Reader, B. F., Jarrett, B. L., McKim, D. B., Wohleb, E. S., Godbout, J. P., & Sheridan, J. F. (2015) · Neuroscience · doi:10.1016/j.neuroscience.2015.01.001 · Cited by 179 · cited 6× · see citing works
“In rodents, the repeated social defeat (RSD) paradigm (Avitsur et al., 2001; Reader et al., 2015) involves placing a large, aggressive rat in the participant rat’s cage for 2 h each day for a week.”
InfluentialDifferential associations between childhood trauma subtypes and adolescent HPA-axis functioning
Kuhlman, K. R., Geiss, E. G., Vargas, I., & Lopez-Duran, N. L. (2015) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2015.01.020 · Cited by 178 · cited 6× · see citing works
“Exposure to physical abuse is also related to exaggerated HPAaxis responses to acute psychosocial stress (Kuhlman et al., 2015a,b) and to viewing violent films among young adolescents (Ivanov et al., 2011).”
InfluentialSelf-citationWynn, J. L., Scumpia, P. O., Winfield, R. D., et al. (2008) · Blood · doi:10.1182/blood-2008-01-130500 · Cited by 175 · cited 1× · see citing works
“For instance, newborn mice exhibited a decreased inflammatory response to infection compared to adult mice (Wynn et al., 2008).”
Interleukin-8 is increased in cerebrospinal fluid of children with severe head injury
Whalen, M. J., Carlos, T. M., Kochanek, P. M., Wisniewski, S. R., Bell, M. J., Clark, R. S. B., DeKosky, S. T., Marion, D. W., & Adelson, D. P. (2000) · Critical Care Medicine · doi:10.1097/00003246-200004000-00003 · Cited by 175 · cited 3× · see citing works
“Some studies have found that LPS stimulation results in similar levels of TNF-α, IL-6, and IL-8 as in adults (Berner et al., 2002; Dembinski et al., 2002; Seghaye et al., 1998), which may be an inconsistency that reflects differences in inflammatory sensitivity to different ligands or bacteria across the human lifespa…”
Effect of gonadal steroids on the production of IL-1 and IL-6 by blood mononuclear cells in vitro.
Li, Z. G., Danis, V. A., & Brooks, P. (1993) · PubMed · Cited by 174 · see citing works
Early childhood adversity and adolescent depression: the mediating role of continued stress
Hazel, N. A., Hammen, C. L., Brennan, P. A., & Najman, J. M. (2008) · Psychological Medicine · doi:10.1017/s0033291708002857 · Cited by 173 · cited 1× · see citing works
“Individuals with adverse experiences in early life continue to perceive more stress, which may be attributed to how they appraise, select, and respond to their environments (Hazel et al., 2008; Miller et al., 2011; Raposa et al., 2014a,b).”
Sripada, R. K., Swain, J. E., Evans, G. W., Welsh, R. C., & Liberzon, I. (2014) · Neuropsychopharmacology · doi:10.1038/npp.2014.75 · Cited by 171 · see citing works
Brand, S. R., Brennan, P. A., Newport, D. J., Smith, A. K., Weiss, T., & Stowe, Z. N. (2010) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2009.10.009 · Cited by 170 · cited 1× · see citing works
“For instance, mothers with a history of depression and early adversity had infants with higher baseline cortisol (Brand et al., 2010), potentially because depression and early adversity can lead to less attentive or detached parenting (Lovejoy et al., 2000; Pereira et al., 2012).”
Bower, J. E., Ganz, P. A., Irwin, M. R., Arevalo, J. M. G., & Cole, S. W. (2010) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2010.09.010 · Cited by 169 · cited 1× · see citing works
“For example, some behavioral interventions effectively reduce proinflammatory gene expression and not necessarily systemic markers (Bower et al., 2014, 2011; Creswell et al., 2012).”
Self-citationBosch, N. M., Riese, H., Reijneveld, S. A., Bakker, M. P., Verhulst, F. C., Ormel, J., & Oldehinkel, A. J. (2012) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2012.01.013 · Cited by 163 · see citing works
Yan, S. R., Qing, G., Byers, D. M., Stadnyk, A. W., Al‐Hertani, W., & Bortolussi, R. A. (2004) · Infection and Immunity · doi:10.1128/iai.72.3.1223-1229.2004 · Cited by 163 · cited 1× · see citing works
“When stimulated with pathogens, monocytes from newborns produced lower levels of IL-6 and TNF-α as adult monocytes (Levy et al., 2004; Pillay et al., 1994; Yan et al., 2004).”
Tajiri, N., Acosta, S. A., Shahaduzzaman, M., Ishikawa, H., Shinozuka, K., Pabon, M. M., Hernandez‐Ontiveros, D. G., Kim, D. W., Metcalf, C., Staples, M., et al. (2013) · Journal of Neuroscience · doi:10.1523/jneurosci.2425-13.2014 · Cited by 162 · cited 1× · see citing works
“This conflicts with the well-characterized neuroinflammation that occurs following traumatic brain injury among adults (Pena et al., 2014; Tajiri et al., 2014).”
Bengtsson, A. K., Ryan, E. J., Giordano, D., Magaletti, D. M., & Clark, E. A. (2004) · Blood · doi:10.1182/blood-2003-10-3380 · Cited by 161 · cited 1× · see citing works
“For instance, estrogen has been shown to increase secretion of IL-6 and IL-8 in dendritic cells derived from monocytes (Bengtsson et al., 2004) whereas estrogen receptor-α treatment inhibits TNF-α and IL-6 (TiwariWoodruff et al., 2007).”
The Psychobiology of Children Exposed to Marital Violence
Saltzman, K. M., Holden, G. W., & Holahan, C. J. (2005) · Journal of Clinical Child & Adolescent Psychology · doi:10.1207/s15374424jccp3401_12 · Cited by 159 · cited 1× · see citing works
“In another study, 8-year-olds exposed to marital violence had higher levels of afternoon cortisol compared to their non-exposed counterparts (Saltzman et al., 2005).”
Sapolsky, R. M., Meaney, M. J., & McEwen, B. S. (1985) · Developmental Brain Research · doi:10.1016/0165-3806(85)90261-5 · Cited by 158 · cited 2× · see citing works
“…example, acceleration of cortisol increase following stress could reflect the intensity of excitatory input into the axis from the limbic system, whereas cortisol regulation following peak more likely reflects the density and sensitivity of GRs, primarily in the hippocampus (Sapolsky et al., 1985).”
Variation in hypothalamic-pituitary-adrenal axis activity among bullied and non-bullied children
Vaillancourt, T., Duku, E., Decatanzaro, D., Macmillan, H., Muir, C., & Schmidt, L. A. (2008) · Aggressive Behavior · doi:10.1002/ab.20240 · Cited by 158 · cited 1× · see citing works
“One study showed that peer victimization within the last three months was associated with lower baseline cortisol among 12-year-olds (Vaillancourt et al., 2008).”
Developmental Change in Infants' Responses to Stress
Lewis, M., & Ramsay, D. S. (1995) · Child Development · doi:10.1111/j.1467-8624.1995.tb00896.x · Cited by 158 · cited 1× · see citing works
“In one longitudinal study, infants mounted a cortisol response to inoculation when 2, 4, and 6 months old, yet the magnitude of the response decreased with age (Lewis and Ramsay, 1995).”
Clinical Potential of Minocycline for Neurodegenerative Disorders
BLUM, D., CHTARTO, A., TENENBAUM, L., BROTCHI, J., & LEVIVIER, M. (2004) · Neurobiology of Disease · doi:10.1016/j.nbd.2004.07.012 · Cited by 157 · cited 1× · see citing works
“Targeted inhibition of microglia using minocycline corresponds to reductions in peripheral inflammation (Blum et al., 2004; O’Connor et al., 2009a,b).”
Social regulation of leukocyte homeostasis: the role of glucocorticoid sensitivity
Cole, S. W. (2008) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2008.02.006 · Cited by 156 · cited 2× · see citing works
“Disrupted caregiving may impair coordination between glucocorticoids and immune cells, such as glucocorticoid insensitivity in immune cells that may contribute to elevated circulating inflammation despite the presence of glucocorticoids (Cole, 2008; Cole et al., 2012).”
Bernard, K., Butzin-Dozier, Z., Rittenhouse, J., & Dozier, M. (2010) · Archives of Pediatrics and Adolescent Medicine · doi:10.1001/archpediatrics.2010.54 · Cited by 156 · cited 1× · see citing works
“For instance, 13-month old maltreated children who were placed in foster care following Child Protective Services involvement displayed steeper diurnal cortisol slopes compared to those who remained with their parents, and likely continued to experience maltreatment (Bernard et al., 2010).”
Dampening of Adrenocortical Responses during Infancy: Normative Changes and Individual Differences
Gunnar, M. R., Brodersen, L., Krueger, K., & Rigatuso, J. (1996) · Child Development · doi:10.2307/1131867 · Cited by 156 · see citing works
Hostinar, C. E., & Gunnar, M. R. (2013) · Journal of Clinical Child & Adolescent Psychology · doi:10.1080/15374416.2013.804387 · Cited by 153 · cited 2× · see citing works
“The HPA-axis and immune system develop significantly in utero (Hostinar and Gunnar, 2013; Simon et al., 2015), and continue to undergo change from the neonatal period through adolescence.”
Gunnar, M. R., Larson, M. C., Hertsgaard, L. A., Harris, M. L., & Brodersen, L. (1992) · Child Development · doi:10.2307/1131479 · Cited by 153 · see citing works
Larson, M. C., White, B. P., Cochran, A., Donzella, B., & Gunnar, M. R. (1998) · Developmental Psychobiology · doi:10.1002/(sici)1098-2302(199812)33:4 · Cited by 150 · see citing works
McLaughlin, K. A., Sheridan, M. A., Alves, S., & Mendes, W. B. (2014) · Psychosomatic Medicine · doi:10.1097/psy.0000000000000098 · Cited by 149 · cited 3× · see citing works
“In line with our proposed framework, different types of stressors differentially impact neuroplasticity (Teicher & Samson, 2013), specifically in the limbic system (Cohen et al., 2013; Wilson et al., 2015), and specifically with regard to processing of threat and rewards (McLaughlin et al., 2014b).”
Childhood parental loss and cortisol levels in adult men
Nicolson, N. A. (2004) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2003.09.005 · Cited by 149 · cited 1× · see citing works
“For example, adults who lost a parent during childhood demonstrated higher cortisol throughout the day compared with adults who never experienced separation from their parents for longer than two weeks (Nicolson, 2004).”
Sumter, S. R., Bokhorst, C. L., Miers, A. C., PELT, J. V., & Westenberg, P. M. (2010) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2010.05.004 · Cited by 146 · cited 1× · see citing works
“Studies of youth have also found that cortisol responses to social stressors increase with age, and are associated with pubertal development (Blumenthal et al., 2014; Gunnar et al., 2009b; Stroud et al., 2009; Sumter et al., 2010; van den Bos et al., 2014).”
Friedman, E. M., Montez, J. K., Sheehan, C. M., Guenewald, T. L., & Seeman, T. E. (2015) · Journal of Aging and Health · doi:10.1177/0898264315580122 · Cited by 145 · cited 3× · see citing works
“Several studies indicate a link between physical trauma and both elevated circulating markers of inflammation and inflammatory diseases (Friedman et al., 2015b).”
Maternal separation induces neuroinflammation and long-lasting emotional alterations in mice
Gracia-Rubio, I., Moscoso-Castro, M., Pozo, O. J., Marcos, J., Nadal, R., & Valverde, O. (2016) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2015.09.003 · Cited by 144 · cited 1× · see citing works
“In particular, rodent studies have demonstrated that early adversity, including maternal separation and early infection, during infancy results in larger, activated microglia, resident immune cells in the brain that secrete inflammatory cytokines (Bilbo, 2013; Gracia-Rubio et al., 2015).”
Pacák, K., Palkovits, M., Květňanský, R., Yadid, G., Kopin, I. J., & Goldstein, D. S. (1995) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.1995.tb44675.x · Cited by 144 · see citing works
Cytokine responses correlate differentially with age in infancy and early childhood
Härtel, C., Adam, N., Strunk, T., Temming, P., Müller-Steinhardt, M., & Schultz, C. (2005) · Clinical and Experimental Immunology · doi:10.1111/j.1365-2249.2005.02928.x · Cited by 143 · see citing works
The neurobiological correlates of childhood adversity and implications for treatment
Tyrka, A. R., Burgers, D. E., Philip, N. S., Price, L. H., & Carpenter, L. L. (2013) · Acta Psychiatrica Scandinavica · doi:10.1111/acps.12143 · Cited by 142 · cited 2× · see citing works
“Yet, in the past decade we have developed a much stronger appreciation for the role childhood environments and experiences in the epigenetic regulation of many components of physiological stress response systems (Anacker et al., 2014; Tyrka et al., 2013).”
The Biological Residue of Childhood Poverty
Miller, G. E., & Chen, E. (2013) · Child Development Perspectives · doi:10.1111/cdep.12021 · Cited by 141 · cited 1× · see citing works
“Of course, part of elevated inflammation among children living in poverty occurs through pathways independent of psychosocial stress such as pollution, pathogen exposure, and limited access to healthcare (See Miller and Chen, 2013 for review).”
Influence of cage enrichment on aggressive behaviour and physiological parameters in male mice
Loo, P. L. P. V., Kruitwagen, C. L. J. J., Koolhaas, J. M., de Weerd, H. A. V., van Zutphen, L. F. M., & Baumans, V. (2002) · Applied Animal Behaviour Science · doi:10.1016/s0168-1591(01)00200-3 · Cited by 136 · cited 1× · see citing works
“…the physiological and developmental consequences of living in an unpredictable environment that causally contribute to complex behavioral phenotypes such as aggression (Van Loo et al., 2002), impaired learning and memory (Holmes and Wellman, 2009), and anhedonia (Gouirand and Matuszewich, 2005).”
Antoni, M. H., Cruess, S. E., Cruess, D. G., Kumar, M., Lutgendorf, S. K., Ironson, G. H., Dettmer, E. L., WILLIAMS, J. R., Klimas, N. G., FLETCHER, M. A., et al. (2000) · Annals of Behavioral Medicine · doi:10.1007/bf02895165 · Cited by 135 · cited 1× · see citing works
“In contrast, there are several cognitive strategies that mitigate threat sensitivity and therefore the frequency and magnitude of SNS and HPAaxis responses to stress (e.g., Antoni et al., 2000).”
Inflammation and early-life abuse in women
Bertone-Johnson, E. R., Whitcomb, B. W., Missmer, S. A., Karlson, E. W., & Rich-Edwards, J. W. (2012) · American Journal of Preventive Medicine · doi:10.1016/j.amepre.2012.08.014 · Cited by 134 · cited 1× · see citing works
“…physical and sexual abuse are not consistently linked with elevated inflammation in adults after accounting for covariates such as BMI and smoking (Bertone-Johnson et al., 2012), suggesting potential behavioral or developmental pathways that may lead from physical trauma to the persistence of…”
Takizawa, R., Danese, A., Maughan, B., & Arseneault, L. (2015) · Psychological Medicine · doi:10.1017/s0033291715000653 · Cited by 134 · see citing works
Flagged first, then by citations
18 of the 288 references couldn’t be matched to a known paper.
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- Raposa, 2014, A developmental pathway from early life stress to inflammation the role of negative health behaviors, Psychol. Sci., 25, 1268, 10.1177/0956797614530570 · DOI
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Rethinking IL-6 and CRP: Why they are more than inflammatory biomarkers, and why it matters
Del Giudice, M., & Gangestad, S. W. (2018) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2018.02.013 · Cited by 779 · see citing works
“…been thought to reflect “glucocorticoid resistance,” a particular kind of dysregulation whereby immune cells (e.g., macrophages) become insensitive to the GR-mediated inhibitory effects of cortisol after prolonged overexposure (Kuhlman et al., 2017; Miller et al., 2002, 2011; Cohen et al., 2012).”
InfluentialEarly life stress and development: potential mechanisms for adverse outcomes
Smith, K. E., & Pollak, S. D. (2020) · Journal of Neurodevelopmental Disorders · doi:10.1186/s11689-020-09337-y · Cited by 500 · see citing works
“is associated with alterations in the immune system and inflammatory activity, which is increasingly implicated in producing shifts in individuals’ behavioral responses to their environment [46, 67].”
BackgroundAgorastos, A., Pervanidou, P., Chrousos, G. P., & Baker, D. G. (2019) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2019.00118 · Cited by 385 · see citing works
“) represent one of the most vulnerable periods in brain development (6, 101, 103, 104).”
BackgroundInfluentialSmith, K. E., & Pollak, S. D. (2020) · Perspectives on Psychological Science · doi:10.1177/1745691620920725 · Cited by 351 · see citing works
“…animal studies suggest that features such as the intensity, severity, chronicity, and developmental timing of adversity are likely to have greater explanatory power compared with the specific type of event an organism endures (Kuhlman et al., 2017; Teicher et al., 2018; Woodard & Pollak, 2020).”
BackgroundIs the HPA Axis as Target for Depression Outdated, or Is There a New Hope?
Menke, A. (2019) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2019.00101 · Cited by 240 · see citing works
“In fact, childhood trauma may lead to an increased sensitivity of the HPA axis and to heightened responses to subsequent stressors (19, 20).”
BackgroundBower, J. (2019) · Cancer · doi:10.1002/cncr.31790 · Cited by 190 · see citing works
“Childhood adversity is known to predict a range of poor mental and physical health outcomes in adulthood,(37) including fatigue in community-dwelling adults,(38,39) and also is linked to inf lammation and other neurologic and neuroendocrine processes relevant for fatigue.(40) Investigators have begun to examine links…”
BackgroundSelf-citationDooley, L. N., Kuhlman, K. R., Robles, T. F., Eisenberger, N. I., Craske, M. G., & Bower, J. E. (2018) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2018.09.006 · Cited by 176 · see citing works
Self-citationKuhlman, K. R., Horn, S. R., Chiang, J. J., & Bower, J. E. (2020) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2019.04.028 · Cited by 163 · see citing works
Self-citationKaess, M., Hooley, J. M., Klimes‐Dougan, B., Koenig, J., Plener, P. L., Reichl, C., Robinson, K., Schmahl, C. G., Sicorello, M., Schreiner, M. W., et al. (2021) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2021.08.022 · Cited by 146 · see citing works
“Although an in-depth discussion of the mechanisms involved in child abuse and neglect is beyond the scope of this review, a large body of literature, which has been summarized in various reviews, has described how chronic child abuse and neglect leads to alterations in the hypothalamic-pituitary-adrenal (HPA) axis (Ku…”
BackgroundUnderstanding Resilience and Preventing and Treating PTSD
Horn, S. R. G.-V., & Feder, A. (2018) · Harvard Review of Psychiatry · doi:10.1097/hrp.0000000000000194 · Cited by 150 · see citing works
“The type and timing of interventions for children are integral to their effectiveness.(251) While several interventions for at-risk youth have been investigated in school-aged children and ado-”
BackgroundSelf-citationA call to action: the second Lancet Commission on adolescent health and wellbeing
Baird, S., Choonara, S., Azzopardi, P. S., Banati, P., Bessant, J., Biermann, O., Capon, A. G., Claeson, M., Collins, P. Y., Wet, N. D., et al. (2025) · The Lancet · doi:10.1016/s0140-6736(25)00503-3 · Cited by 181 · see citing works
Fatigue after breast cancer treatment: Biobehavioral predictors of fatigue trajectories.
Bower, J. E., Wiley, J. F., Petersen, L., Irwin, M. R., Cole, S. W., & Ganz, P. A. (2018) · Health Psychology · doi:10.1037/hea0000652 · Cited by 137 · see citing works
Self-citationModelling resilience in adolescence and adversity: a novel framework to inform research and practice
Malhi, G. S., Das, P., Bell, E., Mattingly, G. W., & Mannie, Z. N. (2019) · Translational Psychiatry · doi:10.1038/s41398-019-0651-y · Cited by 144 · see citing works
Agorastos, A., Pervanidou, P., Chrousos, G. P., & Kolaitis, G. A. (2018) · HORMONES · doi:10.1007/s42000-018-0065-x · Cited by 124 · see citing works
The HPA Axis as Target for Depression
Menke, A. (2024) · Current Neuropharmacology · doi:10.2174/1570159x21666230811141557 · Cited by 131 · see citing works
“In fact, childhood trauma may lead to an increase in HPA axis sensitivity and, thus, to a heightened response to subsequent stressors [28, 29].”
BackgroundChiang, J. J., Lam, P. H., Chen, E., & Miller, G. E. (2022) · Psychological Bulletin · doi:10.1037/bul0000351 · Cited by 126 · see citing works
“…underlying dimensions, such as threat versus deprivation (McLaughlin et al., 2014), harshness versus unpredictability (Belsky et al., 2012), and physical trauma versus disrupted caregiving versus unpredictability (Kuhlman et al., 2017), and that these dimensions have unique influences on outcomes.”
BackgroundSelf-citationFuture Directions in Peer Relations Research
Prinstein, M. J., & Giletta, M. (2020) · Journal of Clinical Child & Adolescent Psychology · doi:10.1080/15374416.2020.1756299 · Cited by 116 · see citing works
“…relations and physiological stress response systems, it will be crucial to adopt a multi-system approach to better understand when and how physiological responses may modify relevant downstream activities at the molecular level (e.g., intracellular inflammatory responses; Kuhlman et al., 2017).”
BackgroundIob, E., Lacey, R. E., & Steptoe, A. (2019) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2019.12.019 · Cited by 86 · see citing works
“5 high co-occurrence of ACEs, the cumulative risk method can only take into account the overlap between different elements of stressful experiences thereby ignoring their potentially different physiological effects (Kuhlman et al., 2017; McLaughlin and Sheridan, 2016).”
Kuhlman, K. R., Robles, T. F., Dooley, L. N., Boyle, C. C., Haydon, M. D., & Bower, J. E. (2018) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2018.02.001 · Cited by 67 · see citing works
Self-citationIob, E., Lacey, R. E., & Steptoe, A. (2020) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2020.07.045 · Cited by 69 · see citing works
“death of a parent, parental separation) for the development of the central nervous system and downstream neuroendocrine and inflammatory responses linked to mental and physical health (Kuhlman et al., 2017).”
BackgroundStress System Activation in Children and Adolescents With Autism Spectrum Disorder
Makris, G., Agorastos, A., Chrousos, G. P., & Pervanidou, P. (2022) · Frontiers in Neuroscience · doi:10.3389/fnins.2021.756628 · Cited by 61 · see citing works
Russell, A. E., Heron, J., Gunnell, D., Ford, T. J., Hemani, G., Joinson, C. J., Moran, P., Relton, C. L., Suderman, M. J., & Mars, B. (2019) · Journal of Child Psychology and Psychiatry · doi:10.1111/jcpp.13100 · Cited by 62 · see citing works
“Alternatively, associations may differ according to the type of ACE experienced, with more biologically salient ACEs such as physical abuse having stronger effects (Kuhlman et al., 2017).”
BackgroundAnnual Research Review: Neuroimmune network model of depression: a developmental perspective
Nusslock, R., Alloy, L. B., Brody, G. H., & Miller, G. E. (2024) · Journal of Child Psychology and Psychiatry · doi:10.1111/jcpp.13961 · Cited by 63 · see citing works
Sigurdardottir, S. L., & Halldórsdóttir, S. (2021) · International Journal of Environmental Research and Public Health · doi:10.3390/ijerph18041849 · Cited by 67 · see citing works
“Psychological trauma caused by sexual violence has long-term health consequences because such stressful experiences can adversely affect the immune response for the rest of the survivor’s life [30-32].”
BackgroundIob, E., Baldwin, J. R., Plomin, R. J., & Steptoe, A. (2021) · Translational Psychiatry · doi:10.1038/s41398-021-01538-w · Cited by 53 · see citing works
“It has been proposed that the HPA-axis and immune systems might respond differently to different types of early life stressors [13, 32, 33].”
BackgroundTan, X., Zhang, X., Pan, L., Tian, X., & Dong, P. (2017) · BioMed Research International · doi:10.1155/2017/4323496 · Cited by 54 · see citing works
Lee, J. H., Espinera, A. R., Chen, D., Choi, K., Caslin, A. Y., Won, S., Pecoraro, V., Xu, G., Wei, L., & Yu, S. P. (2016) · Journal of Neuroinflammation · doi:10.1186/s12974-016-0575-x · Cited by 54 · see citing works
Neglect, HPA axis reactivity, and development
Reilly, E. B., & Gunnar, M. R. (2019) · International Journal of Developmental Neuroscience · doi:10.1016/j.ijdevneu.2019.07.010 · Cited by 56 · see citing works
Childhood trauma dependent anxious depression sensitizes HPA axis function
Menke, A., Lehrieder, D., Fietz, J., Leistner, C., Wurst, C., Stonawski, S., Reitz, J., Lechner, K., Busch, Y., Weber, H., et al. (2018) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2018.07.025 · Cited by 55 · see citing works
“However, while maternal separation is associated with an impaired regulation of the stress response after initiation, physical trauma is associated with exaggerated activation of the stress response (Kuhlman et al., 2017).”
Wu, B., Zhang, H., Chen, J., Chen, J., Liu, Z., Cheng, Y., Yuan, T., & Peng, D. (2023) · General Psychiatry · doi:10.1136/gpsych-2022-100946 · Cited by 55 · see citing works
Schalinski, I., Teicher, M. H., & Rockstroh, B. S. (2019) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2019.06.007 · Cited by 50 · see citing works
Gerke, J., Koenig, A. M., Conrad, D., Doyen-Waldecker, C., Pauly, M., Gündel, H., Wilker, S., & Kolassa, I. (2018) · Mental Health & Prevention · doi:10.1016/j.mhp.2018.03.002 · Cited by 51 · see citing works
Ortega, V. A., Mercer, E. M., Giesbrecht, G. F., & Arrieta, M. (2021) · Frontiers in Microbiology · doi:10.3389/fmicb.2021.634539 · Cited by 51 · see citing works
“Despite differential exposures leading to stress axis dysregulation, the ensuing health consequences exhibit striking similarities, with neuropsychiatric disorders and chronic immune-mediated diseases emerging as common outcomes (Danese et al., 2007; Kuhlman et al., 2017; Agorastos et al., 2018).”
BackgroundEarly Life Stress and Pediatric Posttraumatic Stress Disorder
Pervanidou, P., Makris, G., Chrousos, G. P., & Agorastos, A. (2020) · Brain Sciences · doi:10.3390/brainsci10030169 · Cited by 50 · see citing works
“Thus, ELS exposure together with elevated glucocorticoids levels during the hypo-responsive period could lead to glucocorticoid receptor insensitivity over time, thus affecting the development of a hypo-responsive HPA axis [53].”
BackgroundLacey, R. E., Bartley, M., Kelly‐Irving, M., Bevilacqua, L., Iob, E., Kelly, Y. J., & Howe, L. D. (2020) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2020.104914 · Cited by 50 · see citing works
Cheng, T. W., Mills, K. L., Miranda-Domínguez, Ó., Zeithamová, D., Perrone, A. J., Sturgeon, D., Ewing, S. W. F., Fisher, P. A., Pfeifer, J. H., Fair, D. A., et al. (2020) · Developmental Cognitive Neuroscience · doi:10.1016/j.dcn.2020.100894 · Cited by 47 · see citing works
Testing a biobehavioral model of fatigue before adjuvant therapy in women with breast cancer
Bower, J. E., Asher, A., Garet, D., Petersen, L., Ganz, P. A., Irwin, M. R., Cole, S. W., Hurvitz, S. A., & Crespi, C. M. (2018) · Cancer · doi:10.1002/cncr.31827 · Cited by 49 · see citing works
Self-citationKuhlman, K. R., Robles, T. F., Bower, J. E., & Carroll, J. (2018) · Journal of Behavioral Medicine · doi:10.1007/s10865-018-9921-z · Cited by 49 · see citing works
“…both physical and mental health outcomes in adulthood (Basu et al., 2017; Kessler et al., 2010; Norman et al., 2012), as well as underlying biological processes that presage disease (Jonker et al., 2017; Kuhlman et al., 2015, 2017; Miller et al., 2011; Miller & Chen, 2010; Shonkoff et al., 2009).”
Self-citationChildhood adversity and vagal regulation: A systematic review and meta-analysis
Wesarg, C., van den Akker, A. L., Oei, N. Y. L., Wiers, R. W. H. J., Staaks, J. P. C., Thayer, J. F., Williams, D. P., & Hoeve, M. (2022) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2022.104920 · Cited by 45 · see citing works
“To exemplify, it has been proposed that the degree of covariation be-tween psychological arousal, the HPA axis, and inflammation may predict long-term health outcomes after adversity (Kuhlman et al., 2017).”
BackgroundUsacheva, M., Choe, D. E., Liu, S., Timmer, S., & Belsky, J. (2022) · Development and Psychopathology · doi:10.1017/s0954579422000013 · Cited by 47 · see citing works
“Among possible mechanisms are cellular inflammation and up-regulation of the Hypothalamic-Pituitary-Adrenal (HPA)-axis, linked to disrupted caregiving (Drury et al., 2014; Kuhlman et al., 2017; SturgeApple et al., 2017).”
BackgroundInfluentialChange of pace: How developmental tempo varies to accommodate failed provision of early needs
Roubinov, D. S., Meaney, M. J., & Boyce, W. T. (2021) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2021.09.031 · Cited by 40 · see citing works
Kuhlman, K. R., Robles, T. F., Haydon, M. D., Dooley, L. N., Boyle, C. C., & Bower, J. E. (2019) · Developmental Psychobiology · doi:10.1002/dev.21908 · Cited by 42 · see citing works
Self-citationMenke, A. (2018) · Pharmacogenomics and Personalized Medicine · doi:10.2147/pgpm.s146110 · Cited by 41 · see citing works
Stress impairs response to antidepressants via HPA axis and immune system activation
Menke, A., Nitschke, F., Hellmuth, A., Helmel, J., Wurst, C., Stonawski, S., Blickle, M., Weiß, C., Weber, H., Hommers, L., et al. (2021) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2020.12.033 · Cited by 40 · see citing works
Nazzari, S., Molteni, M., Valtorta, F., Comai, S., & Frigerio, A. (2020) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2020.06.015 · Cited by 36 · see citing works
Annual Research Review: Social relationships and the immune system during development
Robles, T. F. (2020) · Journal of Child Psychology and Psychiatry · doi:10.1111/jcpp.13350 · Cited by 36 · see citing works
Childhood maltreatment and DNA methylation: A systematic review
Rubens, M., Bruenig, D., Adams, J. A. M., Suresh, S. M., Sathyanarayanan, A., Haslam, D. M., Shenk, C. E., Mathews, B., & Mehta, D. (2023) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2023.105079 · Cited by 31 · see citing works
Lai, C., Lee, D. Y., & Leung, M. (2020) · International Journal of Environmental Research and Public Health · doi:10.3390/ijerph18010029 · Cited by 28 · see citing works
“Because of the important role of the HPAA in mediating the stress response, studies examining the connection between CA and cortisol, the end product of the HPAA, have proliferated in the last two decades [6,8].”
BackgroundThe biological underpinnings of perinatal depressive symptoms: A multi-systems approach.
Nazzari, S., Fearon, P. R. M., Rice, F. J., Ciceri, F., Molteni, M., & Frigerio, A. (2020) · Journal of Affective Disorders · doi:10.1016/j.jad.2020.05.023 · Cited by 34 · see citing works
“Besides their individual effects, the stress and inflammatory response systems exhibit significant bidirectional interactions (Kuhlman et al., 2017), with a disruption of these circuits being hypothesized to increase vulnerability to several disorders (Raison and Miller, 2003), including depression…”
BackgroundChildhood maltreatment and monocyte gene expression among women with breast cancer
Bower, J. E., Kuhlman, K. R., Ganz, P. A., Irwin, M. R., Crespi, C. M., & Cole, S. W. (2020) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2020.04.001 · Cited by 33 · see citing works
Self-citationKuhlman, K. R., Robles, T. F., Dickenson, L., Reynolds, B. M., & Repetti, R. L. (2018) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2018.09.033 · Cited by 34 · see citing works
“…indices, namely CAR and diurnal slope, have been prospectively linked to important health out UN CO comes like depression (Adam et al., 2010; Kuhlman et al., 2017b; Vrshek-Schallhorn et al., 2013) and mortality in cancer patients (Schrepf et al., 2015; Sephton et al., 2013, 2000), adoption…”
BackgroundInfluentialSelf-citationThe Consequences of Childhood Emotional Abuse: A Systematic Review and Content Analysis
Korolevskaia, A., & Yampolskaya, S. (2022) · Families in Society The Journal of Contemporary Social Services · doi:10.1177/10443894221124565 · Cited by 34 · see citing works
“Studies have consistently linked disruptive caregiving, such as emotional abuse, to the dysregulation of the hypothalamic–pituitary–adrenal (HPA) axis (Cabrera et al., 2020; Dualibe & Osório, 2017; Kuhlman et al., 2017; Neigh et al., 2009; Palaszynski & Nemeroff, 2009; Yates, 2007).”
BackgroundEarly childhood risk exposures and inflammation in early adolescence
O’Connor, T. G., Willoughby, M. T., Moynihan, J. A., Messing, S. P., Sefair, A. V., Carnahan, J. A., Yin, X., & Caserta, M. T. (2019) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2019.05.001 · Cited by 34 · see citing works
Koenig, A. M., Ramo‐Fernández, L., Boeck, C., Umlauft, M., Pauly, M., Binder, E. B., Kirschbaum, C., Gündel, H., Karabatsiakis, A., & Kolassa, I. (2018) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2018.04.002 · Cited by 31 · see citing works
Oswald, L. M., Dunn, K. E., Seminowicz, D. A., & Storr, C. L. (2021) · Journal of Personalized Medicine · doi:10.3390/jpm11040315 · Cited by 28 · see citing works
Reichl, C., Brunner, R. M., Bender, N., Parzer, P., Koenig, J., Resch, F., & Kaess, M. (2019) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2019.104460 · Cited by 31 · see citing works
Lelli, L., Castellini, G., Cassioli, E., Monteleone, A. M., & Ricca, V. (2019) · Psychiatry Research · doi:10.1016/j.psychres.2019.03.046 · Cited by 30 · see citing works
Boeck, C., Krause, S., Karabatsiakis, A., Schury, K., Gündel, H., Waller, C., & Kolassa, I. (2017) · Development and Psychopathology · doi:10.1017/s0954579417001055 · Cited by 32 · see citing works
Bower, J., Radin, A., & Kuhlman, K. (2022) · Behaviour Research and Therapy · doi:10.1016/j.brat.2022.104104 · Cited by 30 · see citing works
Self-citationEnhanced Immune Activation Following Acute Social Stress Among Adolescents With Early-Life Adversity
Kuhlman, K. R., Cole, S. W., Craske, M. G., Fuligni, A. J., Irwin, M. R., & Bower, J. E. (2022) · Biological Psychiatry Global Open Science · doi:10.1016/j.bpsgos.2022.03.001 · Cited by 32 · see citing works
“Alternatively, the seminal study in adults (ages 18–64 years) (22) focused on childhood maltreatment while this study included more diverse experiences of ELA; thus, maltreatment may specifically contribute to the magnitude of the initial circulating inflammatory response to stress while other forms of ELA shape immun…”
BackgroundSelf-citationSheng, J. A., Tan, S. M. L., Hale, T. M., & Handa, R. J. (2021) · Androgens Clinical Research and Therapeutics · doi:10.1089/andro.2021.0021 · Cited by 30 · see citing works
“males versus females, given that the sex differences have been reported in the function of the HPA axis.(143,144) For example, males are two to three times less likely to develop depression than females(145) and exhibit decreased subclinical symptoms and decreased”
Mayer, S. E., Peckins, M., Kuhlman, K. R., Rajaram, N., Lopez-Duran, N. L., Young, E. A., & Abelson, J. L. (2020) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2020.104776 · Cited by 29 · see citing works
“This is consistent with the idea that different types of abnormalities in the child-rearing environment can differentially shape long-term functioning of the axis (Kuhlman et al., 2017).”
Self-citationMathur, A., Li, J. C., Lipitz, S. R., & Graham‐Engeland, J. E. (2022) · Adversity and Resilience Science · doi:10.1007/s42844-022-00051-3 · Cited by 28 · see citing works
(2024) · doi:10.7554/elife.92700 · Cited by 29 · see citing works
“…adverse experience dimensions that impact distinct neurobiological systems and lead to differential clinical outcomes ( Berens et al., 2017 ; Kuhlman et al., 2017 ; Machlin et al., 2019 ; McLaughlin et al., 2016 ; McLaughlin et al., 2014 ; Sheridan and McLaughlin, 2016 ; Sheridan and…”
BackgroundKyriacou, A., Tziaferi, V., & Toumba, M. (2022) · Hormone Research in Paediatrics · doi:10.1159/000524477 · Cited by 30 · see citing works
Haller, J. (2018) · Frontiers in Systems Neuroscience · doi:10.3389/fnsys.2018.00026 · Cited by 30 · see citing works
Dieckmann, L., Cole, S. W., & Kumsta, R. (2020) · Translational Psychiatry · doi:10.1038/s41398-020-0730-0 · Cited by 33 · see citing works
An Extension to the stress-buffering model: Timing of support across the lifecourse
Lam, P. H. (2024) · Brain Behavior & Immunity - Health · doi:10.1016/j.bbih.2024.100876 · Cited by 25 · see citing works
“Numerous models have proposed how childhood and adolescence stressors can impact physical health e.g., (Miller et al., 2011; Cohen et al., 2016; Repetti et al., 2002; Nusslock and Miller, 2016; Kuhlman et al., 2017).”
BackgroundConley, M. I., Hernandez, J., Salvati, J. M., Gee, D. G., & Baskin-Sommers, A. (2022) · Development and Psychopathology · doi:10.1017/s095457942100184x · Cited by 26 · see citing works
“, 2015) propose that different aspects of youth’s experiences may impact distinct outcomes via specific alterations in biological systems (Kuhlman et al., 2017; McLaughlin & Lambert, 2017; Palacios-Barrios & Hanson, 2019).”
BackgroundMaternal caregiving moderates the impact of antenatal maternal cortisol on infant stress regulation
Nazzari, S., Fearon, P. R. M., Rice, F. J., Molteni, M., & Frigerio, A. (2021) · Journal of Child Psychology and Psychiatry · doi:10.1111/jcpp.13532 · Cited by 26 · see citing works
“Dysregulation of the stress response systems is increasingly regarded as one mechanism through which early adversity ‘gets under the skin’ to influence lifetime physical and mental health (Kuhlman, Chiang, Horn, & Bower, 2017).”
Early-life stress, depressive symptoms, and inflammation: the role of social factors
Nakamura, J. S., Kim, E. S., Rentscher, K. E., Bower, J. E., & Kuhlman, K. R. (2021) · Aging & Mental Health · doi:10.1080/13607863.2021.1876636 · Cited by 26 · see citing works
Self-citationBussone, S., Pesca, C., Tambelli, R., & Carola, V. (2020) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2020.589444 · Cited by 24 · see citing works
“This ability to cope with environmental changes is pivotal for an individual’s survival and matures as a result of the events that are experienced at an early age (48, 49).”
BackgroundChiang, J. J., Chen, E., & Miller, G. E. (2018) · Nature Human Behaviour · doi:10.1038/s41562-018-0316-5 · Cited by 25 · see citing works
“Given that health effects of abuse are hypothesized to differ as a function of the nature and/or severity of the maltreatment 21,22 , we examined different types of abuse (severe physical abuse, moderate physical abuse, and emotional abuse) separately.”
Self-citationMulti-omics in stress and health research: study designs that will drive the field forward
Mengelkoch, S., Gassen, J., Lev‐Ari, S., Alley, J. C., Rose, S. M. S., Snyder, M. P., & Slavich, G. M. (2024) · Stress · doi:10.1080/10253890.2024.2321610 · Cited by 23 · see citing works
“…to early life adversity (e.g. poverty, abuse) is associated with dysregulated hypothalamic-pituitary-adrenal (HPA) axis activity (Heim et al., 2008; Kuhlman et al., 2017; Raymond et al., 2021) and elevated levels of peripheral inflammatory markers (chiang et al., 2022; Milaniak & Jaffee, 2019), as…”
BackgroundEarly adversity as the prototype gene × environment interaction in mental disorders?
Martins, J., Yusupov, N., Binder, E. B., Brückl, T. M., & Czamara, D. (2022) · Pharmacology Biochemistry and Behavior · doi:10.1016/j.pbb.2022.173371 · Cited by 22 · see citing works
Early life stress in women with autoimmune thyroid disorders
Corso, A., Engel, H., Müller, F., Fiacco, S., Mernone, L., Gardini, E., Ehlert, U., & Fischer, S. (2023) · Scientific Reports · doi:10.1038/s41598-023-49993-3 · Cited by 23 · see citing works
“Interestingly, there is evidence that different childhood trauma types lead to different changes in the hypothalamic–pituitary–adrenal axis and in the immune system 44 .”
BackgroundThe role of inflammation in the association between poverty and working memory in childhood
Kokosi, T., Flouri, E., & Midouhas, E. (2020) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2020.105040 · Cited by 21 · see citing works
“Another physiological response to stress is inflammation (Fagundes & Way, 2014; Kuhlman et al., 2017; Minihane et al., 2015), but this has yet to be explored as a possible explanation for the link between economic hardship and poor EF in children.”
BackgroundKuhlman, K. R., Repetti, R. L., Reynolds, B. M., & Robles, T. F. (2018) · Journal of Family Psychology · doi:10.1037/fam0000437 · Cited by 24 · see citing works
Self-citationJohnson, B. N., McKernan, L. C., & Bruehl, S. P. (2022) · Current Pain and Headache Reports · doi:10.1007/s11916-022-01043-9 · Cited by 25 · see citing works
Gilgoff, R., Mengelkoch, S., Elbers, J. M., Kotz, K. J., Radin, A. S., Pasumarthi, I., Murthy, R., Sindher, S., Harris, N. B., & Slavich, G. M. (2024) · Stress · doi:10.1080/10253890.2024.2327333 · Cited by 21 · see citing works
“…et al., 2010; chida et al., 2007; Danese et al., 2007; Danese & lewis, 2017; Kuhlman et al., 2017; Rooks et al., 2012; wei et al., 2012), leading to increased risk of chronic diseases of immune origin (Danese & lewis, 2017; Glaser & Kiecolt-Glaser, 2005; Kuhlman et al., 2017; Mcewen, 2006).”
BackgroundNeuroimmune Advance in Depressive Disorder
Zhao, G., & Liu, X. (2019) · Advances in Experimental Medicine and Biology · doi:10.1007/978-981-32-9271-0_4 · Cited by 20 · see citing works
Fond, G. B., Boyer, L., Andrianarisoa, M., Godin, O., Bulzacka, E., Berna, F. S., Brunel, L., Coulon, N., Aouizerate, B., Capdevielle, D., et al. (2018) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2018.04.007 · Cited by 20 · see citing works
Chat, I. K.-Y., Gepty, A. A., Kautz, M. M., Giollabhui, N. M., Adogli, Z. V., Coe, C. L., Abramson, L. Y., Olino, T. M., & Alloy, L. B. (2022) · Biological Psychiatry Global Open Science · doi:10.1016/j.bpsgos.2022.04.006 · Cited by 18 · see citing works
“Relatedly, developmental timing of stress exposure has moderated the effects of stress on life span health risk and outcome (64), suggesting that the effect of adverse environmental inputs depends on the developmental period of exposure.”
Kimonis, E. R., Fleming, G. E., Wilbur, R. R., Groer, M. E., & Granger, D. A. (2018) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2018.12.228 · Cited by 19 · see citing works
Cohodes, E. M., Sisk, L. M., Keding, T. J., Mandell, J. D., Notti, M. E., & Gee, D. G. (2023) · Development and Psychopathology · doi:10.1017/s0954579423000822 · Cited by 17 · see citing works
“…– including experiential, environmental, and timing attributes – can yield a richer understanding of processes of risk and resilience (Belsky et al., 2012; Cohodes et al., 2021; Ellis et al., 2009, 2022; Gee & Casey, 2015; Kuhlman et al., 2017; Manly et al., 2001; Sheridan & McLaughlin, 2014).”
Bürgin, D., Clemens, V., Varghese, N., Eckert, A., Huber, M., Bruttin, E., Boonmann, C., Unternährer, E., O'Donovan, A., & Schmid, M. (2022) · Brain, Behavior, & Immunity - Health · doi:10.1016/j.bbih.2022.100524 · Cited by 14 · see citing works
Gordon, A., Patterson, T. K., & Knowlton, B. J. (2020) · Neurobiology of Learning and Memory · doi:10.1016/j.nlm.2020.107316 · Cited by 17 · see citing works
Early life stress, subjective social status, and health during late adolescence
Rahal, D., Chiang, J. J., Fales, M. R., Fuligni, A. J., Haselton, M. G., Slavich, G. M., & Robles, T. F. (2020) · Psychology and Health · doi:10.1080/08870446.2020.1761977 · Cited by 18 · see citing works
“…life stress has been linked with greater inflammation, which can serve as a precursor for poorer mental and physical health later in life, as well as greater psychological and inflammatory responses to threat (e.g. Chiang et al., 2015; Kuhlman et al., 2017; Seo et al., 2014; Slavich & Cole, 2013).”
BackgroundSelf-citationCultivating a healthy neuro‐immune network: A health psychology approach
Bower, J. E., Kuhlman, K. R., Haydon, M. D., Boyle, C. C., & Radin, A. S. (2019) · Social and Personality Psychology Compass · doi:10.1111/spc3.12498 · Cited by 20 · see citing works
Self-citationZhang, K., Wang, Y., Sun, Y., Gao, L., Lu, Y., & Wang, N. (2023) · Social Science & Medicine · doi:10.1016/j.socscimed.2023.116510 · Cited by 17 · see citing works
Klem, N.-R., Slater, H., Rowbotham, S. J., Chua, J., Waller, R., Stinson, J., Romero, L., Lord, S. M., Tory, B., Schütze, R., et al. (2024) · Pain · doi:10.1097/j.pain.0000000000003407 · Cited by 16 · see citing works
“21,36,61,72,74,77 Importantly, young people experience significant biologic changes to hypothalamic–pituitary–adrenal (HPA) axis activity.”
Fight Injustice with Darkness: The Effect of Early Life Adversity on Malevolent Creativity Behavior
Geng, Y., Shi, Y., Hu, W., Jin, W., Zhang, Y., & Zhan, T. (2024) · The Journal of Creative Behavior · doi:10.1002/jocb.648 · Cited by 17 · see citing works
Edelmann, S., Wiegand, A., Hentrich, T., Pasche, S., Schulze-Hentrich, J. M., Munk, M. H. J., Fallgatter, A. J., Kreifelts, B., & Nieratschker, V. (2023) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2023.1125553 · Cited by 15 · see citing works
“Furthermore, dysregulation of the—inflammatory—immune response through childhood stress exposure can affect brain development, cognition, stress reactivity and resilience and, hence, the risk for psychopathology later in life [9-12].”
BackgroundJuvenile confinement exacerbates adversity burden: A neurobiological impetus for decarceration
Orendain, N., Galván, A., Smith, E., Barnert, E. S., & Chung, P. J. (2022) · Frontiers in Neuroscience · doi:10.3389/fnins.2022.1004335 · Cited by 18 · see citing works
“Youth from low SES households have higher basal cortisol levels (Kuhlman et al., 2018), neural alterations similar to those associated with early life adversity exposure (Hanson et al.”
BackgroundBürgin, D., Varghese, N., Eckert, A., Clemens, V., Unternäehrer, E., Boonmann, C., O’Donovan, A., & Schmid, M. (2022) · Scientific Reports · doi:10.1038/s41598-022-14905-4 · Cited by 15 · see citing works
Kempel, M. K., Winding, T. N., Bøttcher, M., & Andersen, J. H. (2022) · BMC Public Health · doi:10.1186/s12889-022-13158-0 · Cited by 14 · see citing works
“Both early, middle and late childhood are mentioned as powerful periods due to neurobiological and social developmental processes that might influence the individual for life [14, 15].”
BackgroundSemsar, N., Mousavi, Z. A., Tran, M.-L. M., & Kuhlman, K. R. (2021) · Child Abuse & Neglect · doi:10.1016/j.chiabu.2021.105306 · Cited by 14 · see citing works
Self-citationMorse, L. M., Kober, K. M., Viele, C. S., Cooper, B. A., Paul, S. M., Conley, Y. P., Hammer, M. J., Levine, J. D., & Miaskowski, C. A. (2021) · Supportive Care in Cancer · doi:10.1007/s00520-021-06410-7 · Cited by 14 · see citing works
Kuhlman, K. R. (2023) · Brain Behavior & Immunity - Health · doi:10.1016/j.bbih.2023.100711 · Cited by 17 · see citing works
“This is the basic premise of the ELS theory on biological salience (See Kuhlman et al., 2017 for review); different forms of adversity vary in their relevance to different psycho-physiological systems within a developing individual, and varying forms of adversity may shape the development of that…”
BackgroundSelf-citationHahnefeld, A., Sukale, T., Weigand, E., Münch, K., Aberl, S., Eckler, L. V., Schmidt, D., Friedmann, A., Plener, P. L., Fegert, J. M., et al. (2021) · BMC Psychiatry · doi:10.1186/s12888-021-03233-y · Cited by 13 · see citing works
“[9] conclude that children growing up in conditions of unpredictable events show increased neural”
BackgroundInfluential
- Authors
- Kuhlman, K. R., Chiang, J. J., Horn, S., & Bower, J. E.
- Affiliations
- University of California, Los Angeles (US)
- Northwestern University (US)
- University of Oregon (US)
- Corresponding author
- Kuhlman, Kate Ryan
- Venue
- Neuroscience & Biobehavioral Reviews
- Publisher
- Elsevier BV
- Published
- 2017-09
- Volume
- 80
- Pages
- 166-184
- ISSN
- 0149-7634 (ISSN-L)
- PMC
- PMC5705276
- OpenAlex
- W2620868499
- Cited by
- 208
- References
- 288
- Citations by year
- 2026: 13 · 2025: 14 · 2024: 25 · 2023: 31 · 2022: 31 · 2021: 23 · 2020: 26 · 2019: 22 · 2018: 20 · 2017: 2 · 2016: 1
- FWCI
- 1.69
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Neuroscience & Biobehavioral Reviews (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- National Institute of Mental Health (K08MH112773, T32MH015750)
- Topics
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Social Sciences › Psychology › Clinical Psychology › Child Abuse and Trauma
- Social Sciences › Psychology › Clinical Psychology › Resilience and Mental Health
- Keywords
- childhood adversity, hypothalamic-pituitary-adrenal axis, unpredictable environments, physical threats, developmental framework
- MeSH terms
- Animals, Humans, Hypothalamo-Hypophyseal System, Inflammation, Pituitary-Adrenal System, Adult Survivors of Child Abuse
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