BackgroundPosttraumatic stress disorder (PTSD) is associated with an enhanced risk for cardiovascular and other inflammatory diseases. Chronic low-level inflammation has been suggested as a potential mechanism linking these conditions.MethodsWe investigated plasma cytokine levels as well as spontaneous and lipopolysaccharide (LPS)-stimulated cytokine production by peripheral blood mononuclear cells (PBMCs) in a group of 35 severely traumatized PTSD patients compared to 25 healthy controls.ResultsSpontaneous production of interleukin (IL)-1β, IL-6 and tumor necrosis factor (TNF)-α by isolated PBMCs was significantly higher in the PTSD compared to the control group and even correlated with PTSD symptom severity within the PTSD group. In contrast, circulating plasma levels of pro- and anti-inflammatory cytokines such as IL-6, IL-8, IL-10, TNF-α, or monocyte chemotactic protein (MCP)-1 were not significantly altered in PTSD patients compared to healthy controls.ConclusionsOur findings indicate that PBMCs of PTSD patients are already pre-activated in vivo, providing further evidence for low-grade inflammation in PTSD. This might possibly represent one psychobiological pathway from PTSD to poor physical health.

Posttraumatic stress disorder (PTSD) is associated with an enhanced susceptibility to various somatic diseases. However, the exact mechanisms linking traumatic stress to subsequent physical health problems have remained unclear. This study investigated peripheral T lymphocyte differentiation subsets in 19 individuals with war and torture related PTSD compared to 27 non-PTSD controls (n=14 trauma-exposed controls; n=13 non-exposed controls). Peripheral T cell subpopulations were classified by their characteristic expression of the lineage markers CD45RA and CCR7 into: naïve (CD45RA(+) CCR7(+)), central memory (T(CM): CD45RA(-) CCR7(+)) and effector memory (T(EM): CD45RA(-) CCR7(-) and T(EMRA): CD45RA(-) CCR7(-)) cells. Furthermore, we analyzed regulatory T cells (CD4(+)CD25(+)FoxP3(+)) and ex vivo proliferation responses of peripheral blood mononuclear cells after stimulation with anti-CD3 monoclonal antibody. Results show that the proportion of naïve CD8(+) T lymphocytes was reduced by 32% (p=0.01), whereas the proportions of CD3(+) central (p=0.02) and effector (p=0.01) memory T lymphocytes were significantly enhanced (+22% and +34%, respectively) in PTSD patients compared to non-PTSD individuals. To a smaller extent, this effect was also observed in trauma-exposed non-PTSD individuals, indicating a cumulative effect of traumatic stress on T cell distribution. Moreover, PTSD patients displayed a 48% reduction in the proportion of regulatory T cells (p<0.001). Functionally, these alterations were accompanied by a significantly enhanced (+34%) ex vivo proliferation of anti-CD3 stimulated T cells (p=0.05). The profoundly altered composition of the peripheral T cell compartment might cause a state of compromised immune responsiveness, which may explain why PTSD patients show an increased susceptibility to infections, and inflammatory and autoimmune diseases.

BackgroundLittle is known about the neurobiological foundations of psychotherapy for Posttraumatic Stress Disorder (PTSD). Prior studies have shown that PTSD is associated with altered processing of threatening and aversive stimuli. It remains unclear whether this functional abnormality can be changed by psychotherapy. This is the first randomized controlled treatment trial that examines whether narrative exposure therapy (NET) causes changes in affective stimulus processing in patients with chronic PTSD.Methods34 refugees with PTSD were randomly assigned to a NET group or to a waitlist control (WLC) group. At pre-test and at four-months follow-up, the diagnostics included the assessment of clinical variables and measurements of neuromagnetic oscillatory brain activity (steady-state visual evoked fields, ssVEF) resulting from exposure to aversive pictures compared to neutral pictures.ResultsPTSD as well as depressive symptom severity scores declined in the NET group, whereas symptoms persisted in the WLC group. Only in the NET group, parietal and occipital activity towards threatening pictures increased significantly after therapy.ConclusionsOur results indicate that NET causes an increase of activity associated with cortical top-down regulation of attention towards aversive pictures. The increase of attention allocation to potential threat cues might allow treated patients to re-appraise the actual danger of the current situation and, thereby, reducing PTSD symptoms.Registration of the clinical trialNumber: NCT00563888Name: "Change of Neural Network Indicators Through Narrative Treatment of PTSD in Torture Victims" ULR: http://www.clinicaltrials.gov/ct2/show/NCT00563888

The increased early activity in the right prefrontal cortex most likely represents an enhanced alarm response or the fear network toward aversive stimuli in PTSD, whereas the subsequent decreased activation in right parieto-occipital areas in response to aversive pictures seems to reflect the tendency to disengage from emotional content. This finding is consistent with the hypothesis of a vigilance-avoidance reaction pattern to threat in anxiety disorders and helps to reconcile contradicting results of over- and under-responsiveness in the sensory processing of threatening stimuli in PTSD.

The influence of past traumatic experiences on the defense cascade in response to affective pictures was examined in survivors of war and torture. Trauma-exposed refugees with and without Posttraumatic Stress Disorder (PTSD) as well as healthy individuals viewed 75 pictures that varied in emotional content. Heart rate (HR) was recorded during the flickering stimulation of affective pictures in the context of a steady-state experiment. Whereas healthy controls showed the typical orienting response to aversive stimuli, PTSD patients reacted with an almost immediate increase in HR toward unpleasant pictures. Trauma-exposed participants without PTSD showed an indiscriminate orienting response regardless of picture category. The present findings argue for a faster flight/fight response to threatening cues in PTSD. In contrast, trauma-exposed controls seem to exhibit a state of permanent alertness toward a wide range of stimuli.