Altered Stress-Induced Regulation of Genes in Monocytes in Adults with a History of Childhood Adversity

Abstract

Exposure to serious or traumatic events early in life can lead to persistent alterations in physiological stress response systems, including enhanced cross talk between the neuroendocrine and immune system. These programming effects may be mechanistically involved in mediating the effects of adverse childhood experience on disease risk in adulthood. We investigated hormonal and genome-wide mRNA expression responses in monocytes to acute stress exposure, in a sample of healthy adults (n = 30) with a history of early childhood adversity, and a control group (n = 30) without trauma experience. The early adversity group showed altered hypothalamus-pituitaryadrenal axis responses to stress, evidenced by lower ACTH and cortisol responses. Analyses of gene expression patterns showed that stress-responsive transcripts were enriched for genes involved in cytokine activity, cytokine-cytokine receptor interaction, chemokine activity, and G-protein coupled receptor binding. Differences between groups in stress-induced regulation of gene transcription were observed for genes involved in steroid binding, hormone activity, and G-protein coupled receptor binding. Transcription factor binding motif analysis showed an increased activity of pro-inflammatory upstream signaling in the early adversity group. We also identified transcripts that were differentially correlated with stress-induced cortisol increases between the groups, enriched for genes involved in cytokine-cytokine receptor interaction and glutamate receptor signaling. We suggest that childhood adversity leads to persistent alterations in transcriptional control of stress-responsive pathways, which-when chronically or repeatedly activated-might predispose individuals to stress-related psychopathology.

Adverse life events increase risk for postpartum psychiatric episodes: A population-based epidemiologic study

“…The negative experience of sustaining multiple adverse life events throughout childhood could result in multiple biologic changes by increasing allostatic load, or the cumulative stress on the body that is a sum of lifetime stress exposure (Geronimus, Hicken, Keene, & Bound, 2006). Possible explanations for this could be lasting alterations of the hypothalamic pituitary adrenal stress axis reactivity (Wilkinson & Goodyer, 2011), and other biologic changes including epigenetic modification (Perroud et al, 2011), persistent alterations in transcriptional control of stress-responsive pathways (Schwaiger et al, 2016), and shortened telomere length (Vincent et al, 2017).…”

HPA axis dysregulation in adult adoptees twenty years after severe institutional deprivation in childhood

“…However, given findings by other groups who have prospectively assessed HPA axis function in institutionalized and post-institutionalized children (Koss et al, 2016;McLaughlin et al, 2015), and given our own findings of early appearing deprivationspecific problems which are highly persistent and are not eradicated by the overall very positive post-adoption experience, it is likely that HPA axis dysregulation also constitutes an early appearing and stable phenotype associated with institutional rearing. In light of the evidence of decreased cortisol activity and reactivity in adults and children with experience of early adversity (Carpenter et al, 2007;Elzinga et al, 2008;Lovallo et al, 2011;Miller et al, 2007;Power et al, 2012;Schwaiger et al, 2016), it has been proposed that sustained periods of chronic stress, such as psychosocial deprivation and neglect, are initially associated with high levels of circulating cortisol, followed by counter-regulation which eventually results in decreased HPA axis re-/ activity. This attenuation hypothesis (Trickett et al, 2010) is supported by a meta-analysis showing that the more time that had elapsed since trauma emerged, the lower a person's cortisol levels (Miller et al, 2007).…”

“…It has been challenging to validate these results in humans given justifiable constraints on exposing participants to adverse experiences. Although the majority of studies in adults reporting adversity in childhood have found HPA axis dysregulations (Carpenter et al, 2007;Elzinga et al, 2008;Lovallo et al, 2011;MacMillan et al, 2009;Power et al, 2012;Schwaiger et al, 2016), linking these effects to early life adversity per se, rather than, for instance, later emerging mental health problems is problematic, given the retrospective, and potentially questionable nature of the reports of the nature and timing of exposures .…”

Social history and exposure to pathogen signals modulate social status effects on gene regulation in rhesus macaques

“…This relationship is thought to arise in part through changes in gene regulation, which mediate the genomic response to physiological signals of social stress (e.g., glucocorticoids, adrenaline, noradrenaline; (6,7)). Gene expression signatures of social status and social adversity have now been reported in multiple studies, encompassing clinical and population-based samples in humans, and studies of both experimental and natural populations in other social animals (6,(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)) (see also (20)(21)(22)(23)(24)(25) for evidence in social insects and other social vertebrates). Because this work has concentrated most extensively on peripheral white blood cells, it provides a direct window into how social experiences are reflected in the regulation of the immune system (26)(27)(28).…”