Posttraumatic stress disorder is associated with an enhanced spontaneous production of pro-inflammatory cytokines by peripheral blood mononuclear cells
2013, Gola, Hannah, Engler, Harald, Sommershof, Annette, Adenauer, Hannah, Kolassa, Stephan, Schedlowski, Manfred, Gröttrup, Marcus, Elbert, Thomas, Kolassa, Iris-Tatjana
Posttraumatic 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. METHODS: We 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. RESULTS: Spontaneous production of interleukin (IL)-1beta, IL-6 and tumor necrosis factor (TNF)-alpha 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-alpha, or monocyte chemotactic protein (MCP)-1 were not significantly altered in PTSD patients compared to healthy controls.
Our 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.
Substantial reduction of naïve and regulatory T cells following traumatic stress
2009, Sommershof, Annette, Aichinger, Hannah, Engler, Harald, Adenauer, Hannah, Catani, Claudia, Boneberg, Eva-Maria, Elbert, Thomas, Gröttrup, Marcus, Kolassa, Iris-Tatjana
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 traumaexposed 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 (TCM: CD45RA- CCR7+) and effector memory (TEM: CD45RA- CCR7- and TEMRA: 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.
Victims of rape show increased cortisol responses to trauma reminders : a study in individuals with war- and torture-related PTSD
2012-02, Gola, Hannah, Engler, Harald, Schauer, Maggie, Adenauer, Hannah, Riether, Carsten, Kolassa, Stephan, Elbert, Thomas, Kolassa, Iris-Tatjana
Studies investigating cortisol responses to trauma-related stressors in patients with posttraumatic stress disorder (PTSD) have yielded inconsistent results, demonstrating that cortisol responses were enhanced or unaffected when confronted with trauma reminders. This study investigated the effect of the type of trauma experienced on both salivary and plasma cortisol responses during confrontation with trauma-related material. Participants were 30 survivors of war and torture, with and without rape among the traumatic events experienced. Participants of both groups (raped vs. non-raped) fulfilled DSM-IV criteria of PTSD. Plasma and salivary cortisol levels were measured at three time points during a standardized clinical interview: once before and twice after assessing individual traumatic experiences. Results show that groups did not differ in basal plasma and salivary cortisol levels. However, differential salivary cortisol responses were observed in PTSD patients who had been raped compared to those who had not been raped (p < .05) but had experienced an equal number of traumatic events and showed equally high PTSD symptom severity. Whereas salivary cortisol levels decreased in the course of the interview for the group with no past experience of rape (p < .05), those PTSD patients who had been raped showed a significant cortisol increase when reminded of their traumatic events (p < .001). This effect was not found in plasma cortisol. Our results indicate that the type of traumatic stress experienced contributes to cortisol responses during the confrontation with trauma-related material. We hypothesize, that the nearness of the perpetrator during the traumatic event might shape later psychophysiological responding to trauma reminders.
No PTSD-related differences in diurnal cortisol profiles of genocide survivors
2009, Eckart, Cindy, Engler, Harald, Riether, Carsten, Kolassa, Stephan, Elbert, Thomas, Kolassa, Iris-Tatjana
Posttraumatic stress disorder (PTSD) has been associated with reduced cortisol levels. Opposing results have been interpreted as resulting from methodological differences between studies.We investigated the diurnal profile of salivary cortisol in a population of highly traumatized adult males from Rwanda with and without PTSD, who spent the whole day of examination together under amaximally standardized schedule. Besides the detection of PTSDrelated alterations in cortisol release we aimed at determining physiologically relevant effects of cumulative trauma exposure on HPA functioning in interaction with or independent of diagnosis. There were no differences in the diurnal pattern of cortisol release between subjects with and without PTSD. We observed an increasing prevalence of PTSD with increasing number of different traumatic event types experienced, replicating earlier results on a building-block effect of multiple traumatization. However, size of cumulative exposure was not related to any of the cortisol measures. The results suggest that besides methodological constraints also confounding factors not previously controlled for, e.g., sex differences or current life stress, might contribute to the diverging results of lowered, unchanged or enhanced cortisol secretion in PTSD. Future research should therefore closely monitor these possible confounds to optimize models for cortisol in research on stress-dependent illnesses.
Increased cortisol concentrations in hair of severely traumatized Ugandan individuals with PTSD
2011-09, Steudte, Susann, Kolassa, Iris-Tatjana, Stalder, Tobias, Pfeiffer, Anett, Kirschbaum, Clemens, Elbert, Thomas
Previous research has mostly suggested general hypocortisolism in posttraumatic stress disorder (PTSD). However, PTSD is a complex disorder and opposite neuroendocrinological changes have also been reported. Amongst other things, heterogeneous results might be related to differences in sample characteristics as well as methodological factors associated with the assessment of cortisol. The current study used the novel method of hair cortisol analysis to examine cumulative long-term cortisol secretion in a severely traumatized PTSD sample. Hair samples of 10 traumatized individuals with PTSD and 17 traumatized controls without PTSD from a civil war area of Northern Uganda were analyzed. Results revealed that hair samples of PTSD participants contained higher cortisol levels than those of traumatized controls (p < .05). Furthermore, a positive association between hair cortisol levels and the number of lifetime traumatic events was found (p < .05). The current hair cortisol findings suggest that PTSD in severely traumatized individuals who continue to live under stressful conditions might be associated with general hypercortisolism. Future research examining participants after traumatic events at different follow-up periods is needed to determine the specific influence of time interval since traumatization.