Childhood trauma and adulthood inflammation: a meta-analysis of peripheral C-reactive protein, interleukin-6 and tumour necrosis factor-α

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.

Section: Introductionmentioning

confidence: 92%

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

Schwaiger

Grinberg

Moser

et al. 2016

“…The association was not explained by key potential confounders, such as low birth weight, disadvantaged socio-economic conditions of the family, and low IQ, or by potential mediators, such as adult stressors, poor adult health, unhealthy behaviors, or acute infections at the time of inflammation assessment. Two dozen independent studies have since tested this association, and qualitative and quantitative reviews found reliable evidence of small elevations in inflammation biomarkers in maltreated individuals (Baumeister et al, 2015;Coelho et al, 2014). Of note, elevated inflammation levels are observed not only after maltreatment by adults, but also after other common and severe childhood stressors, such as bullying by peers (Takizawa et al, 2015).…”

Section: Brain Developmentmentioning

confidence: 98%

Psychoneuroimmunology of Early-Life Stress: The Hidden Wounds of Childhood Trauma?

Danese

Lewis

2016

297

191

The brain and the immune system are not fully formed at birth, but rather continue to mature in response to the postnatal environment. The two-way interaction between the brain and the immune system makes it possible for childhood psychosocial stressors to affect immune system development, which in turn can affect brain development and its long-term functioning. Drawing from experimental animal models and observational human studies, we propose that the psychoneuroimmunology of early-life stress can offer an innovative framework to understand and treat psychopathology linked to childhood trauma. Earlylife stress predicts later inflammation, and there are striking analogies between the neurobiological correlates of early-life stress and of inflammation. Furthermore, there are overlapping trans-diagnostic patterns of association of childhood trauma and inflammation with clinical outcomes. These findings suggest new strategies to remediate the effect of childhood trauma before the onset of clinical symptoms, such as anti-inflammatory interventions and potentiation of adaptive immunity. Similar strategies might be used to ameliorate the unfavorable treatment response described in psychiatric patients with a history of childhood trauma.

“…Specifically, increased circulating concentrations of interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF)-α, and the acute phase reactant C-reactive protein (CRP) are all significantly associated with trauma exposure as shown in a recent meta-analysis (Tursich et al, 2014). The majority of these studies have specifically assessed the influence of childhood maltreatment and adversity on inflammation in adulthood (Baumeister et al, 2015;Lin et al, 2016). Indeed, individuals who were exposed to childhood maltreatment, as well as those exposed to difficult family and socio-economic circumstances in childhood (Taylor et al, 2006), show heightened levels of CRP in adulthood (Bertone-Johnson et al, 2012;Danese et al, 2007;Lin et al, 2016;Matthews et al, 2014;Rooks et al, 2012;Tietjen et al, 2012).…”

Section: Ptsd and Inflammationmentioning

confidence: 99%

Inflammation in Fear- and Anxiety-Based Disorders: PTSD, GAD, and Beyond

Michopoulos

Powers

Gillespie

et al. 2016

528

376

The study of inflammation in fear-and anxiety-based disorders has gained interest as growing literature indicates that proinflammatory markers can directly modulate affective behavior. Indeed, heightened concentrations of inflammatory signals, including cytokines and C-reactive protein, have been described in posttraumatic stress disorder (PTSD), generalized anxiety disorder (GAD), panic disorder (PD), and phobias (agoraphobia, social phobia, etc.). However, not all reports indicate a positive association between inflammation and fear-and anxiety-based symptoms, suggesting that other factors are important in future assessments of inflammation's role in the maintenance of these disorders (ie, sex, co-morbid conditions, types of trauma exposure, and behavioral sources of inflammation). The most parsimonious explanation of increased inflammation in PTSD, GAD, PD, and phobias is via the activation of the stress response and central and peripheral immune cells to release cytokines. Dysregulation of the stress axis in the face of increased sympathetic tone and decreased parasympathetic activity characteristic of anxiety disorders could further augment inflammation and contribute to increased symptoms by having direct effects on brain regions critical for the regulation of fear and anxiety (such as the prefrontal cortex, insula, amygdala, and hippocampus). Taken together, the available data suggest that targeting inflammation may serve as a potential therapeutic target for treating these fear-and anxiety-based disorders in the future. However, the field must continue to characterize the specific role pro-inflammatory signaling in the maintenance of these unique psychiatric conditions.