Stress and trauma-associated immunological changes and their implications on health


Chronischer und traumatischer Stress, wie er von Personen erlebt wurde, die unter einer Posttraumatischen Belastungsstörung (PTSD) leiden, ist assoziiert mit schlechter körperlicher Gesundheit, erhöhter Inanspruchnahme medizinischer Leistungen, und erhöhtem Risiko für eine Vielzahl körperlicher Erkrankungen wie kardiovaskuläre, inflammatorische und Autoimmunerkrankungen. Stress steht zudem im Zusammenhang mit einer erhöhten Mutagenese und einer verminderten DNA-Reparatur-Fähigkeit und damit mit einem erhöhten Risiko für Krebs. Zusammenfassend zeigen PTSD-Patienten eine hohe Morbidität und ein hohes Risiko für die Entwicklung einer Vielzahl von körperlichen Erkrankungen. Ziel dieses Projekts ist es, die Beziehung zwischen der Schwere eines Stressors und den assoziierten immunologischen Veränderungen genauer zu beleuchten sowie die funktionellen Implikationen der beobachteten immunologischen Veränderungen für die physische Gesundheit zu untersuchen.

  • FB Psychologie
  • Zukunftskolleg
    Kolassa, Iris; Kolassa, Stephan; Ertl, Verena; Papassotiropoulos, Andreas; Quervain, Dominique J.-F. de(2010): The Risk of Posttraumatic Stress Disorder After Trauma Depends on Traumatic Load and the Catechol-O-Methyltransferase Val158Met Polymorphism Biological Psychiatry ; 67 (2010), 4. - S. 304-308

The Risk of Posttraumatic Stress Disorder After Trauma Depends on Traumatic Load and the Catechol-O-Methyltransferase Val158Met Polymorphism

Background<br />The risk for posttraumatic stress disorder (PTSD) depends on the number of traumatic event types experienced in a dose response relationship, but genetic factors are known to also influence the risk of PTSD. The catechol-O-methyltransferase (COMT) Val158Met polymorphism has been found to affect fear extinction and might play a role in the etiology of anxiety disorders.<br />Methods<br />Traumatic load and lifetime and current diagnosis of PTSD and COMT genotype were assessed in a sample of 424 survivors of the Rwandan Genocide living in the Nakivale refugee camp in southwestern Uganda.<br />Results<br />Higher numbers of different lifetime traumatic event types led to a higher prevalence of lifetime PTSD in a dose response relationship. However, this effect was modulated by the COMT genotype: whereas Val allele carriers showed the typical dose response relationship, Met/Met homozygotes exhibited a high risk for PTSD independently of the severity of traumatic load.<br />Conclusions<br />The present findings indicate a gene environment interaction between the human COMT Val158Met polymorphism and the number of traumatic event types experienced in the risk of developing PTSD.

Origin (projects)

    Kolassa, Iris; Ertl, Verena; Eckart, Cindy; Glöckner, Franka; Kolassa, Stephan; Papassotiropoulos, Andreas; Quervain, Dominique J.-F. de; Elbert, Thomas(2010): Association Study of Trauma Load and SLC6A4 Promoter Polymorphism in Posttraumatic Stress Disorder : Evidence From Survivors of the Rwandan Genocide Journal of Clinical Psychiatry ; 71 (2010), 5. - S. 543-547

Association Study of Trauma Load and SLC6A4 Promoter Polymorphism in Posttraumatic Stress Disorder : Evidence From Survivors of the Rwandan Genocide

Objective: As exposure to different types of traumatic stressors increases, the occurrence of posttraumatic stress disorder (PTSD) increases. However, because some people exhibit either surprising resilience or high vulnerability, further influencing factors have been conjectured, such as gene-environment interactions. The SLC6A4 gene, which encodes serotonin transporter, has been identified as predisposing toward differential emotional processing between genotypes of its promoter polymorphism.<br />Method: We investigated 408 refugees from the Rwandan genocide and assessed lifetime exposure to traumatic events, PTSD (according to DSM-IV) status, and genotype of the SLC6A4 promoter polymorphism. The study was conducted from March 2006 to February 2007.<br />Results: The prevalence of PTSD approached<br />100% when traumatic exposure reached extreme levels. However, persons homozygous for the short allele of the SLC6A4 promoter polymorphism showed no dose-response relationship but were at high risk for developing PTSD after very few traumatic events. This genotype influence vanished with increasing exposure to traumatic stressors. Conclusion: We find evidence for a geneenvironment interplay for PTSD and show that genetic influences lose importance when environmental factors cause an extremely high trauma burden to an individual. In the future, it may be important to determine whether the effectiveness of therapeutic interventions in PTSD is also modulated by the SLC6A4 genotype.

Origin (projects)

    Eckart, Cindy; Engler, Harald; Riether, Carsten; Kolassa, Stephan; Elbert, Thomas; Kolassa, Iris-Tatjana(2009): No PTSD-related differences in diurnal cortisol profiles of genocide survivors Psychoneuroendocrinology ; 34 (2009), 4. - S. 523-531

No PTSD-related differences in diurnal cortisol profiles of genocide survivors

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.

Origin (projects)

  Sommershof, Annette; Aichinger, Hannah; Engler, Harald; Adenauer, Hannah; Catani, Claudia; Boneberg, Eva-Maria; Elbert, Thomas; Groettrup, Marcus; Kolassa, Iris-Tatjana(2009): Substantial reduction of naïve and regulatory T cells following traumatic stress Brain, Behavior, and Immunity ; 23 (2009), 8. - S. 1117-1124. - ISSN 0889-1591. - eISSN 1090-2139

Substantial reduction of naïve and regulatory T cells following traumatic stress

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.
  Kolassa, Iris-Tatjana; Jurisch, Florentine; Elbert, Thomas(2009): Traumatisierte Therapeuten? : Ein Überblick über sekundäre Traumatisierung Zeitschrift für Klinische Psychologie & Psychotherapie ; 38 (2009), 4. - S. 250-261

Traumatisierte Therapeuten? : Ein Überblick über sekundäre Traumatisierung

Kolassa, Iris-Tatjana; Jurisch, Florentine; Elbert, Thomas

Origin (projects)

    Kolassa, Iris-Tatjana; Eckart, Cindy; Ruf, Martina; Neuner, Frank; Quervain, Dominique J. F. de; Elbert, Thomas(2007): Lack of cortisol response in patients with posttraumatic stress disorder (PTSD) undergoing a diagnostic interview BMC Psychiatry ; 7 (2007), 1. - 54. - eISSN 1471-244X

Lack of cortisol response in patients with posttraumatic stress disorder (PTSD) undergoing a diagnostic interview

Background<br />According to DSM-IV, the diagnosis of posttraumatic stress disorder (PTSD) requires the experience of a traumatic event during which the person's response involved intense fear, helplessness, or horror. In order to diagnose PTSD, clinicians must interview the person in depth about his/her previous experiences and determine whether the individual has been traumatized by a specific event or events. However, asking questions about traumatic experiences can be stressful for the traumatized individual and it has been cautioned that subsequent "re-traumatization" could occur. This study investigated the cortisol response in traumatized refugees with PTSD during a detailed and standardized interview about their personal war and torture experiences.<br /><br />Methods<br />Participants were male refugees with severe PTSD who solicited an expert opinion in the Psychological Research Clinic for Refugees of the University of Konstanz. 17 patients were administered the Vivo Checklist of War, Detention, and Torture Events, a standardized interview about traumatic experiences, and 16 subjects were interviewed about absorption behavior. Self-reported measures of affect and arousal, as well as saliva cortisol were collected at four points. Before and after the experimental intervention, subjects performed a Delayed Matching-to-Sample (DMS) task for distraction. They also rated the severity of selected PTSD symptoms, as well as the level of intrusiveness of traumatic memories at that time.<br /><br />Results<br />Cortisol excretion diminished in the course of the interview and showed the same pattern for both groups. No specific response was detectable after the supposed stressor. Correspondingly, ratings of subjective well-being, memories of the most traumatic event(s) and PTSD symptoms did not show any significant difference between groups. Those in the presumed stress condition did not perform worse than persons in the control condition after the stressor. However, both groups performed poorly in the DMS task, which is consistent with memory and concentration problems demonstrated in patients with PTSD.

Origin (projects)

    Kolassa, Iris-Tatjana; Wienbruch, Christian; Neuner, Frank; Schauer, Maggie; Ruf, Martina; Odenwald, Michael; Elbert, Thomas(2007): Altered oscillatory brain dynamics after repeated traumatic stress BMC Psychiatry ; 7 (2007), 1. - 56. - eISSN 1471-244X

Altered oscillatory brain dynamics after repeated traumatic stress

Background:<br />Repeated traumatic experiences, e.g. torture and war, lead to functional and structural cerebral changes, which should be detectable in cortical dynamics. Abnormal slow waves produced within circumscribed brain regions during a resting state have been associated with lesioned neural circuitry in neurological disorders and more recently also in mental illness.<br />Methods<br /><br />Using magnetoencephalographic (MEG-based) source imaging, we mapped abnormal distributions of generators of slow waves in 97 survivors of torture and war with posttraumatic stress disorder (PTSD) in comparison to 97 controls.<br /><br />Results:<br />PTSD patients showed elevated production of focally generated slow waves (1 4 Hz), particularly in left temporal brain regions, with peak activities in the region of the insula. Furthermore, differential slow wave activity in right frontal areas was found in PTSD patients compared to controls.<br /><br />Conclusion:<br />The insula, as a site of multimodal convergence, could play a key role in understanding the pathophysiology of PTSD, possibly accounting for what has been called posttraumatic alexithymia, i.e., reduced ability to identify, express and regulate emotional responses to reminders of traumatic events. Differences in activity in right frontal areas may indicate a dysfunctional PFC, which may lead to diminished extinction of conditioned fear and reduced inhibition of the amygdala.

Origin (projects)

    Quervain, Dominique J. F. de; Kolassa, Iris-Tatjana; Ertl, Verena; Onyut, Lamaro Patience; Neuner, Frank; Elbert, Thomas; Papassotiropoulos, Andreas(2007): A deletion variant of the alpha2b-adrenoceptor is related to emotional memory in Europeans and Africans Nature Neuroscience ; 10 (2007), 9. - S. 1137-1139. - ISSN 1097-6256. - eISSN 1546-1726

A deletion variant of the alpha2b-adrenoceptor is related to emotional memory in Europeans and Africans

Emotionally arousing events are recalled better than neutral events. This phenomenon, which helps us to remember important and potentially vital information, depends on the activation of noradrenergic transmission in the brain. Here we show that a deletion variant of ADRA2B, the gene encoding the a2b-adrenergic receptor, is related to enhanced emotional memory in healthy Swiss subjects and in survivors of the Rwandan civil war who experienced highly aversive emotional situations.

Origin (projects)

Funding sources
NameProject no.DescriptionPeriod
Emmy-Noether-Programm427/09Emmy-Noether-Nachwuchsförderungno information
Further information
Period: 04.12.2008 – 04.12.2013