Increased peripheral NF-κB pathway activity in women with childhood abuse-related posttraumatic stress disorder

Pace, Thaddeus W.W.; Wingenfeld, Katja; Schmidt, Iris; Meinlschmidt, Gunther; Hellhammer, Dirk H.; Heim, Christine

doi:10.1016/j.bbi.2011.07.232

Cited by 168 publications

(122 citation statements)

References 24 publications

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“…In older subjects, chronic caregiving stress was related to both heightened IL-6 levels and shorter telomere length only in survivors of ELS (Kiecolt-Glaser et al, 2011). Moreover, ELS is a significant predictor of lipopolysaccharide-stimulated IL-6, decreased glucocorticoid sensitivity (Miller and Chen, 2010), and increased DNA binding of the main inflammatory transcription factor nuclear factor κB in patients who suffer from ELS-associated posttraumatic stress disorder or MDD (Pace et al, 2006; Pace et al, 2012). Whether alterations in the OT-immune cross-talk are involved in the ELS-depression relationship has yet to be established, but certainly yields potential for new insights into the etiology of ELS-associated depression.…”

Section: Ot and Early-life Stress (Els) – Role In Shaping Neural Cmentioning

confidence: 99%

“…The mechanisms through which information about pre-conceptional and gestational stressors are conveyed to the fetus likely include MPF stress biology (Entringer et al, 2015). Given the fact that ELS-exposed individuals show marked alterations in stress responsive systems such as the HPA axis (Heim et al, 2008) and the immune system (Pace et al, 2012), it is highly plausible that these conditions may extend to the gestational period and provide cues about maternal ELS to her unborn child and shape its developmental trajectory. Some preliminary evidence supports the notion that MPF endocrine stress biology is altered in the context of maternal ELS.…”

Section: Ot Pathways In the Intergenerational Transmission Of Matementioning

confidence: 99%

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Oxytocin pathways in the intergenerational transmission of maternal early life stress

Toepfer

Heim

Entringer

et al. 2017

Neuroscience & Biobehavioral Reviews

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Severe stress in early life, such as childhood abuse and neglect, constitutes a major risk factor in the etiology of psychiatric disorders and somatic diseases. Importantly, these long-term effects may impact the next generation. The intergenerational transmission of maternal early life stress (ELS) may occur via pre-and postnatal pathways, such as alterations in maternal-fetal-placental stress physiology, maternal depression during pregnancy and postpartum, as well as impaired mother-offspring interactions. The neuropeptide oxytocin (OT) has gained considerable attention for its role in modulating all of these assumed transmission pathways. Moreover, central and peripheral OT signaling pathways are highly sensitive to environmental exposures and may be compromised by ELS with implications for these putative transmission mechanisms. Together, these data suggest that OT pathways play an important role in the intergenerational transmission of maternal ELS in humans. By integrating recent studies on gene-environment interactions and epigenetic modifications in OT pathway genes, the present review aims to develop a conceptual framework of intergenerational transmission of maternal ELS that emphasizes the role of OT.

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Section: Ot and Early-life Stress (Els) – Role In Shaping Neural Cmentioning

confidence: 99%

Section: Ot Pathways In the Intergenerational Transmission Of Matementioning

confidence: 99%

Oxytocin pathways in the intergenerational transmission of maternal early life stress

Toepfer

Heim

Entringer

et al. 2017

Neuroscience & Biobehavioral Reviews

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“…Alterations in the transcriptional patterns of expression for genes involved in inflammatory pathways have also been associated with PTSD (Segman et al, 2005;Yehuda et al, 2009;Zieker et al, 2007). Nuclear factor-κB (NFκB), signal transducer and activator of transcription 5B, and nuclear factor I/A are all critical transcription factors with substantive roles in the activation of cytokine responses to challenge whose activity is increased in the presence of PTSD (Guardado et al, 2016;O'Donovan et al, 2011;Pace et al, 2012;Sarapas et al, 2011). Gene expression of the proinflammatory cytokine IL-18 and its receptor IL-18R1 is decreased in individuals with PTSD (Mehta et al, 2011;Segman et al, 2005;Zieker et al, 2007).…”

Section: Ptsd and Inflammationmentioning

confidence: 99%

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

Michopoulos

Powers

Gillespie

et al. 2016

Neuropsychopharmacol

545

376

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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.

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“…For example, exposure to repeated life stressors or laboratory stressors involving social conflict, threat, isolation, and rejection increases inflammatory markers including C-reactive protein (CRP), interleukin-6 (IL-6), interleukin-1β (IL-1β) and soluble tumor necrosis factor-α receptor (TNFsr) in the blood (Aschbacher et al, 2012;Denson et al, 2009;Dickerson et al, 2009;Steptoe et al, 2007) and NF-κB mRNA (a transcription factor for inflammatory proteins) in leukocytes (Murphy et al, 2013;Pace et al, 2012). This elevated inflammatory state has also been associated with increased risk and severity of mood disorders including depression (Aschbacher et al, 2012;Danese et al, 2008;Pace et al, 2012). …”

Section: Clinical Evidence Linking Inflammation and Stress-related Momentioning

confidence: 99%

Danger Signals and Inflammasomes: Stress-Evoked Sterile Inflammation in Mood Disorders

Fleshner

Frank

Maier

2016

Neuropsychopharmacol

183

125

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Major depressive disorder (MDD) and other mood disorders remain difficult to effectively treat, and innovative interventions and therapeutic targets are needed. Psychological stressors and inappropriate inflammation increase the risk and severity of mood disorders; however, only recently have the importance of sterile inflammatory processes in this effect been revealed. This review will introduce the reader to pathogen vs sterile inflammation, inflammatory receptor-ligand interactions, microbialassociated molecular patterns (MAMPs), pathogen-associated molecular patterns (PAMPs), danger-associated molecular patterns (DAMPs), and the more recent discovery of the role of the inflammasome in peripheral and central nervous system cytokine/chemokine inflammatory responses. The review will focus on current preclinical and clinical evidence that sterile inflammation and inflammasome-dependent signaling may contribute to mood disorders. By understanding these inflammatory signaling processes, new approaches for quieting chronic or inappropriate inflammatory states may be revealed and this could serve as novel pharmacological targets for the treatment of mood disorders.

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Increased peripheral NF-κB pathway activity in women with childhood abuse-related posttraumatic stress disorder

Cited by 168 publications

References 24 publications

Oxytocin pathways in the intergenerational transmission of maternal early life stress

Oxytocin pathways in the intergenerational transmission of maternal early life stress

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

Danger Signals and Inflammasomes: Stress-Evoked Sterile Inflammation in Mood Disorders

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