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.
A deletion variant of the alpha2b-adrenoceptor is related to emotional memory in Europeans and Africans
2007, Quervain, Dominique J. F. de, Kolassa, Iris-Tatjana, Ertl, Verena, Onyut, Lamaro Patience, Neuner, Frank, Elbert, Thomas, Papassotiropoulos, Andreas
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.
Lack of cortisol response in patients with posttraumatic stress disorder (PTSD) undergoing a diagnostic interview
2007, Kolassa, Iris-Tatjana, Eckart, Cindy, Ruf-Leuschner, Martina, Neuner, Frank, Quervain, Dominique J. F. de, Elbert, Thomas
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.
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.
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.
Interpretive bias in social phobia : An ERP study with morphed emotional schematic faces
2009, Kolassa, Iris-Tatjana, Kolassa, Stephan, Bergmann, Sandra, Lauche, Romy, Dilger, Stefan, Miltner, Wolfgang H. R., Musial, Frauke
Individuals with social phobia fear negative evaluation, which is most directly
signalled by an angry expression of the interlocutor s face. This study investigated the processing of 3 series of schematic emotional faces, which were morphed in 7 steps from a neutral face to an angry, happy, or sad face by systematically varying features of the mouth, eyes, and eyebrows. Individuals with social phobia or spider phobia rated angry faces as more arousing than controls. Social phobics did not identify angry faces faster and showed no greater latent trait to identify a face as angry than controls. ERP data showed a modulation of the face-specific N170 by facial emotion, although this did not discriminate social phobics from controls. Instead, phobic subjects exhibited generally increased visual P1 amplitudes, suggesting a state of hypervigilance for incoming stimuli. Results are discussed in the context of psychophysiological abnormalities in the anxiety disorder spectrum.
Structural and functional neuroplasticity in relation to traumatic stress
2007, Kolassa, Iris-Tatjana, Elbert, Thomas
The body's stress response is an essential adaptive and protective mechanism to cope with threatening situations. However, chronic or traumatic stress leads to structural and functional alterations in the traumatized brain. We argue for a building-block effect: Exposure to different types of traumatic events increases the probability of developing posttraumatic stress disorder (PTSD), via incremental enlargement of a fear network. We summarize evidence of brain changes in PTSD, including recent results from research on animal models of stress-related neuroplastic remodeling, with an emphasis on structural and functional changes in the hippocampus, the amygdala, and the medial prefrontal cortex.
Altered oscillatory brain dynamics after repeated traumatic stress
2007, Kolassa, Iris-Tatjana, Wienbruch, Christian, Neuner, Frank, Schauer, Maggie, Ruf-Leuschner, Martina, Odenwald, Michael, Elbert, Thomas
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.
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.
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.
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.
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.
Event-related potentials to schematic faces in social phobia
2007, Kolassa, Iris-Tatjana, Kolassa, Stephan, Musial, Frauke, Miltner, Wolfgang H.
Social phobia has been associated with an attentional bias for angry faces. This study aimed at further characterising this attentional bias by investigating reaction times, heart rates, and ERPs while social phobics, spider phobics, and controls identified either the colour or the emotional quality of angry, happy, or neutral schematic faces. The emotional expression of angry faces did not interfere with the processing of their colour in social phobics, and heart rate, N170 amplitude and parietal late positive potentials (LPPs) of these subjects were also no different from those of non-phobic subjects. However, social phobics showed generally larger P1 amplitudes than non-phobic controls with spider phobic subjects in between. No general threat advantage for angry faces was found. All groups identified neutral schematic faces faster and showed larger late positive amplitudes to neutral than to emotional faces. Furthermore, in all groups the N170 was modulated by the emotional quality of faces. This effect was most pronounced in the emotion identification task.
A case of spider phobia in a congenitally blind person
2007, Musial, Frauke, Kolassa, Iris-Tatjana, Sülzenbrück, Sandra, Miltner, Wolfgang H. R.
Vision is the key sensory system in humans, leading to the implicit assumption that the acquisition of spider phobia is predominantly mediated through the visual pathway. We report on a congenitally blind person with spider phobia, showing that the acquisition of spider phobia does not necessarily depend on visual cues.