Journal ArticleDOI
Increased peripheral NF-κB pathway activity in women with childhood abuse-related posttraumatic stress disorder ☆
Thaddeus W.W. Pace,Katja Wingenfeld,Iris Schmidt,Gunther Meinlschmidt,Dirk H. Hellhammer,Christine Heim +5 more
Reads0
Chats0
TLDR
It is suggested that enhanced inflammatory system activity in participants with childhood abuse-related PTSD is observable at the level of NF-κB, and that in general decreased immune cell glucocorticoid sensitivity may contribute to increased NF-kkB pathway activity.Abstract:
In addition to neuroendocrine changes PTSD pathophysiology may also involve dysfunction of the innate immune inflammatory system. PTSD patients have been found to exhibit increased concentrations of circulating inflammatory markers such as C-reactive protein and interleukin-6, suggesting dysfunction of the innate immune inflammatory system. However, few studies have investigated molecular signaling pathways known to critically regulate inflammation. Additionally, the relationship between inflammatory function and immune cell glucocorticoid sensitivity has not been extensively explored in PTSD. Nuclear factor-?B (NF-?B) pathway activity was examined in peripheral blood mononuclear cells obtained from 12 women with childhood abuse-related PTSD and 24 healthy controls (ages 19-48) using DNA-binding ELISA. Glucocorticoid sensitivity of monocytes in whole blood was measured as the concentration of dexamethasone needed to suppress in vitro lipopolysaccharide-induced tumor necrosis factor-alpha production by 50% (DEX IC(50)). Women with PTSD displayed increased NF-?B pathway activity compared to controls (t [34]=2.45, p=0.02) that was positively correlated with PTSD severity (determined by PTSD symptom severity scale) (r(s)=0.39, p=0.02). Increased NF-?B pathway activity was associated with increased whole blood monocyte DEX IC(50) (i.e. decreased sensitivity of monocytes to glucocorticoids) across all participants (r=0.66, p>0.001). These findings suggest that enhanced inflammatory system activity in participants with childhood abuse-related PTSD is observable at the level of NF-?B, and that in general decreased immune cell glucocorticoid sensitivity may contribute to increased NF-?B pathway activity. Enhanced inflammation may contribute to co-morbid somatic disease risk in persons with childhood abuse-related PTSD.read more
Citations
More filters
Journal ArticleDOI
From Stress to Inflammation and Major Depressive Disorder: A Social Signal Transduction Theory of Depression
TL;DR: A biologically plausible, multilevel theory is proposed that describes neural, physiologic, molecular, and genomic mechanisms that link experiences of social-environmental stress with internal biological processes that drive depression pathogenesis and may shed light on several important questions including how depression develops, why it frequently recurs, and why it is strongly predicted by early life stress.
Journal ArticleDOI
Allele-specific FKBP5 DNA demethylation mediates gene-childhood trauma interactions
Torsten Klengel,Divya Mehta,Christoph Anacker,Monika Rex-Haffner,Jens C. Pruessner,Carmine M. Pariante,Thaddeus W.W. Pace,Kristina B. Mercer,Helen S. Mayberg,Bekh Bradley,Bekh Bradley,Charles B. Nemeroff,Florian Holsboer,Christine Heim,Christine Heim,Kerry J. Ressler,Kerry J. Ressler,Theo Rein,Elisabeth B. Binder +18 more
TL;DR: It is found that a functional polymorphism altering chromatin interaction between the transcription start site and long-range enhancers in the FK506 binding protein 5 gene increased the risk of developing stress-related psychiatric disorders in adulthood by allele-specific, childhood trauma–dependent DNA demethylation in functional glucocorticoid response elements of FKBP5.
Journal ArticleDOI
Cytokine targets in the brain: impact on neurotransmitters and neurocircuits
TL;DR: The effects of inflammatory cytokines on the brain represent an orchestrated suite of behavioral and immune responses that subserve evolutionary priorities to shunt metabolic resources away from environmental exploration to fighting infection and wound healing, while also maintaining vigilance against attack, injury, and further pathogen exposure.
Journal ArticleDOI
Inflammation in Fear- and Anxiety-Based Disorders: PTSD, GAD, and Beyond.
Vasiliki Michopoulos,Vasiliki Michopoulos,Abigail Powers,Charles F. Gillespie,Kerry J. Ressler,Tanja Jovanovic +5 more
TL;DR: The available data suggest that targeting inflammation may serve as a potential therapeutic target for treating fear- and anxiety-based disorders in the future, but the field must continue to characterize the specific role pro-inflammatory signaling in the maintenance of these unique psychiatric conditions.
References
More filters
Journal ArticleDOI
Cytokine-Associated Emotional and Cognitive Disturbances in Humans
Abraham Reichenberg,Raz Yirmiya,Andreas Schuld,Thomas Kraus,Monika Haack,Abraham Morag,Thomas Pollmächer +6 more
TL;DR: In humans, a mild stimulation of the primary host defense has negative effects on emotional and memory functions, which is probably caused by cytokine release, and cytokines represent a novel target for neuropsychopharmacological research.
Journal ArticleDOI
Childhood maltreatment predicts adult inflammation in a life-course study
TL;DR: Childhood maltreatment is a previously undescribed, independent, and preventable risk factor for inflammation in adulthood, and may be an important developmental mediator linking adverse experiences in early life to poor adult health.
Journal ArticleDOI
A mechanism converting psychosocial stress into mononuclear cell activation.
Angelika Bierhaus,Jutta M. Wolf,Martin Andrassy,Nicolas Rohleder,Per M. Humpert,Dmitry Petrov,Roman Ferstl,Maximilian von Eynatten,Thoralf Wendt,Gottfried Rudofsky,Martina Joswig,Michael Morcos,Markus Schwaninger,Bruce S. McEwen,Clemens Kirschbaum,Peter P. Nawroth +15 more
TL;DR: Noradrenaline-dependent adrenergic stimulation results in activation of NF-κB in vitro and in vivo, which represents a downstream effector for the neuroendocrine response to stressful psychosocial events and links changes in the activity of the neuro endocrine axis to the cellular response.
Journal ArticleDOI
Posttraumatic stress disorder and physical illness: results from clinical and epidemiologic studies.
TL;DR: Assessment of the association between chronic PTSD in a national sample of Vietnam veterans and the prevalence of common autoimmune diseases suggests that chronic PTSD, particularly comorbid PTSD or complex PTSD, is associated with all of these conditions.
Journal ArticleDOI
Neurobiological and psychiatric consequences of child abuse and neglect
TL;DR: Most patients who have experienced early traumatic experiences are likely best treated with a combination of psychotherapy and pharmacotherapy, and the few current treatment outcome studies relevant to this research area are described.