Immunologische und molekularbiologische Veränderungen bei Patienten mit Posttraumatischer Belastungsstörung und die mögliche Einflussnahme durch Psychotherapie

The experience of traumatic life events has severe consequences on both psychological and physiological health. In particular, there is an augmented probability for the development of a posttraumatic stress disorder (PTSD) (Kolassa, Ertl, et al., 2010; Neuner, Schauer, Karunakara, et al., 2004), as well as for numerous of physical diseases (Felitti et al., 1998), with a cumulative number of traumatic life events. Therefore, individuals with PTSD present an increased risk for cardiovascular, infectious-, autoimmune diseases and cancer (Boscarino, 2004; Glaesmer et al., 2011). Previous research indicated extensive biological alterations concerning the endocrine- and the immune system in individuals with PTSD (Pace & Heim, 2011). Since many of these biological alterations are age-dependent and normally occur in people in old age (Ershler & Keller, 2000; Fagnoni et al., 2000), this might point towards an association between psychological stress and premature biological aging (Bosch et al., 2009; Epel, 2009; Graham et al., 2006). Furthermore, the question remains if the biological alterations found in individuals with PTSD are specific for the diagnosis of PTSD, or if also individuals who experienced traumatic events, but did not develop a PTSD show stress-induced biological alterations. In this way, there might be a cumulative effect of traumatic load on biological alterations.The aim of the present thesis is to investigate, in a first step, the impact of traumatic load on biological alterations in individuals with PTSD, and to analyze in a second step the exertion of influence through psychotherapy. Immunological and molecular alterations were analyzed in severely traumatized refugees with multiple trauma exposure through war and organized violence. The control group included persons with a background of migration, but without traumatic load and without psychiatric diseases. To test the hypothesis of a dose-response effect of traumatic load on biological alterations, all three studies included an additional group with substantial trauma-exposure, but without the diagnosis of PTSD.In study 1 of this thesis, the findings of a reduced proportion in naïve cytotoxic (CD8+) and regulatory T cells, as well as an increase in the proportion of memory CD8+ T cells, were approved in an expansion of the sample from Sommershof et al. (2009) of 34 individuals with PTSD, 24 trauma-exposed and 19 control subjects. Moreover, there was evidence for a dose-response effect of traumatic load on the alterations in T Lymphocyte distribution. In a second step, it was investigated if effective psychotherapeutic treatment can cause a normalization of the altered T Lymphocyte distribution in individuals with PTSD. Psychotherapeutic treatment included 12 sessions of Narrative Exposure Therapy (NET), which has been verified as an effective trauma-focused treatment approach in several studies (Robjant & Fazel, 2010). To analyze the effectiveness of NET on psychological and biological changes, 34 individuals with PTSD were randomly assigned to either a treatment group or a waitlist control group. Four months after the end of treatment, PTSD symptom severity and somatic complaints improved significantly in the NET group, and even improved further in the one-year follow-up. One year after the end of treatment, there was also a significant increase in the proportion of regulatory T cells, however the altered proportions of naïve and memory CD8+ T cells did not change through psychotherapeutic treatment. The results indicate not only an improvement in psychological symptoms, but also a normalization of the altered regulatory T Lymphocyte distribution through psychotherapeutic treatment.In study 2, damage and repair of the DNA has been investigated in 34 individuals with PTSD, 11 trauma-exposed and 20 control subjects. It was demonstrated that individuals with PTSD showed a significantly accelerated amount of DNA damage compared to controls, with a cumulative effect of trauma load on DNA damage. Against expectations, the repair of damaged DNA was not impaired in individuals with PTSD, but rather was improved in capacity. The influence of psychotherapeutic treatment with NET on DNA damage and repair was investigated in a sample of 38 individuals with PTSD who were randomly assigned to either a treatment or a waitlist control group. Four months after the end of treatment, there was significant improvement not only in PTSD symptom severity but also in DNA damage in the NET treatment group, however not in the waitlist control group. DNA repair capacity changed analogue with the amount of DNA damage and normalized after the end of treatment. The results demonstrate that psychotherapeutic treatment is effective even on a molecular level and, since carcinogenesis is considerably related to DNA damage, the reduction of DNA damage is a relevant factor to prevent the physical health of individuals with PTSD.Both the shift in the proportion of cytotoxic T cells, as well as the increase in DNA damage are characteristic for age-dependent alterations that normally occur in old people (Fagnoni et al., 2000; Lombard et al., 2005). Therefore, in study 3 the hypothesis of premature biological aging in individuals with PTSD was tested with the GlycoAge test. The GlycoAge test describes an age-dependent profile of N-glycosylation that has been identified as a marker for physiological aging by Vanhooren et al., (2010). Therefore, the N-glycosylation profile of 13 individuals with PTSD, 9 trauma-exposed and 10 control subjects was analyzed with the GlycoAge test. Individuals with PTSD differed significantly from controls in their N-glycosylation profile and presented a shift in the GlycoAge test, which would be representative for individuals about 15 years older. Moreover, also with respect to the N-glycosylation profile, a dose-response effect of traumatic load appeared.In conclusion, the findings of the three studies demonstrate a cumulative effect of traumatic load on immunological and molecular alterations as well as a process of premature biological aging in individuals with PTSD. Moreover, and most importantly it has been shown that effective trauma-focused psychotherapeutic treatment not only improved psychological health, but also contributed to a normalization of the immunological and molecular alterations in individuals with PTSD