Association of polygenic risk scores, traumatic life events and coping strategies with war-related PTSD diagnosis and symptom severity in the South Eastern Europe (SEE)-PTSD cohort.

OBJECTIVES: Posttraumatic stress disorder (PTSD) is triggered by extremely stressful environmental events and characterized by high emotional distress, re-experiencing of trauma, avoidance and hypervigilance. The present study uses polygenic risk scores (PRS) derived from the UK Biobank (UKBB) mega-cohort analysis as part of the PGC PTSD GWAS effort to determine the heritable basis of PTSD in the South Eastern Europe (SEE)-PTSD cohort. We further analyzed the relation between PRS and additional disease-related variables, such as number and intensity of life events, coping, sex and age at war on PTSD and CAPS as outcome variables. METHODS: Association of PRS, number and intensity of life events, coping, sex and age on PTSD were calculated using logistic regression in a total of 321 subjects with current and remitted PTSD and 337 controls previously subjected to traumatic events but not having PTSD. In addition, PRS and other disease-related variables were tested for association with PTSD symptom severity, measured by the Clinician Administrated PTSD Scale (CAPS) by liner regression. To assess the relationship between the main outcomes PTSD diagnosis and symptom severity, each of the examined variables was adjusted for all other PTSD related variables. RESULTS: The categorical analysis showed significant polygenic risk in patients with remitted PTSD and the total sample, whereas no effects were found on symptom severity. Intensity of life events as well as the individual coping style were significantly associated with PTSD diagnosis in both current and remitted cases. The dimensional analyses showed as association of war-related frequency of trauma with symptom severity, whereas the intensity of trauma yielded significant results independently of trauma timing in current PTSD. CONCLUSIONS: The present PRS application in the SEE-PTSD cohort confirms modest but significant polygenic risk for PTSD diagnosis. Environmental factors, mainly the intensity of traumatic life events and negative coping strategies, yielded associations with PTSD both categorically and dimensionally with more significant p-values. This suggests that, at least in the present cohort of war-related trauma, the association of environmental factors and current individual coping strategies with PTSD psychopathology was stronger than the polygenic risk.

Molecular Mechanisms of Posttraumatic Stress Disorder (PTSD) as a Basis for Individualized and Personalized Therapy: Rationale, Design and Methods of the South Eastern Europe (SEE)-PTSD study.

Posttraumatic Stress Disorder (PTSD) is a major health problem in South Eastern Europe (SEE). Available treatment options are not efficient enough and the course is often chronic. Little is known about molecular mediators and moderators of pathogenesis and therapy. Genetic and epigenetic variation may be one central molecular mechanism. We therefore established a consortium combining clinical expertise on PTSD from SEE countries Bosnia-Herzegovina (Sarajevo, Tuzla and Mostar), Kosovo (Prishtina) and Croatia (Zagreb) with genetic and epigenetic competence from Germany (Würzburg) in 2011 within the framework of the DAAD (Deutscher Akademischer Austauschdienst)-funded Stability Pact for South Eastern Europe. After obtaining ethical votes and performing rater trainings as well as training in DNA extraction from EDTA blood between 2011 and 2013, we recruited 747 individuals who had experienced war-related trauma in the SEE conflicts between 1991 and 1999. 236 participants had current PTSD, 161 lifetime PTSD and 350 did not have and never had PTSD. Demographic and clinical data are currently merged together with genetic and epigenetic data in a single database to allow for a comprehensive analysis of the role of genetic and epigenetic variation in the pathogenesis and therapy of PTSD. Analyses will be done to a great degree by PhD students from participating SEE centers who in addition to participation in the project had an opportunity to take part in spring and summer schools of the DFG (Deutsche Forschungsgemeinschaft) funded Research Training Group (RTG) 1253 and thus meet PhD students from Germany and other countries We are confident that our project will not only contribute to a better understanding of genetic and epigenetic mechanisms of PTSD as a basis for future individualized and personalized therapies, but also to the academic development of South Eastern Europe.

Treatment outcomes and costs at specialized centers for the treatment of PTSD after the war in former Yugoslavia.

OBJECTIVE: Posttraumatic stress disorder (PTSD) is a frequent consequence of war experience, and specialized centers have been established in some war-affected areas to provide treatment. This study assessed treatment costs and outcomes in such centers in former Yugoslavia. METHODS: An observational study was conducted in four specialized treatment centers (in Serbia, Croatia, and Bosnia-Herzegovina). A total of 526 consecutive adult patients with war-related PTSD were assessed at the beginning of treatment, and 463 met inclusion criteria, including a diagnosis of PTSD on the Clinician-Administered PTSD Scale for DSM-IV (CAPS). For most patients seven years had elapsed between the traumatic experience and treatment at the specialized center. Service costs were also assessed. Outcomes measured at one year were the presence of a PTSD diagnosis and severity of symptoms as indicated by the CAPS score and subjective quality of life as measured by the Manchester Short Assessment of Quality of Life. RESULTS: At 12 months 380 (82%) patients were followed up, and 325 (86%) met criteria for PTSD. Symptoms and quality of life showed overall small but statistically significant improvements. Treatment costs for patients with and without PTSD at 12 months did not significantly differ (euro 307 and euro 284, respectively). CONCLUSIONS: The recovery rate among patients treated in specialized centers for war-related PTSD several years after the war was poor (14%), and symptom improvements were small. The recovery rate was not linked to service costs. Improving recovery rates might require different treatment methods or different service models.

[Quality of life and coping strategies caharacteristics within war torture survivors]. / Karakteristike kvaliteta zivota i koping strategija prezivjelih ratnu torturu.

AIM: The aim of this research is evaluation of the life quality and the coping strategies of the war torture survivors, which were included in the multidisciplinary rehabilitation program in the Center for torture victims in Sarajevo. METHOD: The research is analytical-descriptive and retrospective. In the study we used the sample consisting of 48 persons who survived the war torture. Two instruments were used in the research: for the evaluation of the life quality we used the Manchester Quality of Life Scale (MANSA), and the other instrument is the reviewed (according to Ljubotina) original Lazarus-Folkman Coping Scale. RESULTS: The results related to the life quality are showing that evaluating satisfaction with life as a whole where the largest score in the total sample is achieved by the answer "both satisfied and unsatisfied". The results show a high score of discontent with financial situation, and a prevailing satisfaction with accommodation. Significant data are related to prevailing satisfaction with life within the family. The examinees, largely males, showed "mostly unsatisfied" with their somatic health, while the situation with evaluation of the mental health with both genders and in total sample was estimated as "mostly unsatisfied" and as "both satisfied and unsatisfied". The results that emerged from applying the Coping Scale show that in the total sample, especially more expressed in females, social support is used as a coping strategy in post trauma conditions. The lowest score is achieved in the subscale of avoidance/escape. DISCUSSION: Results of this study related to quality of life characteristics within war torture survivors indicates moderate satisfaction with life generally, and emphasizes lower satisfaction with their financial situation. It is very important to be stressed out high level of satisfaction with relationship with family members. According to the results of the study it is clear that difficult socioeconomic conditions in post war period significantly influence satisfaction with life in general, and impact of such conditions on somatic and mental health of war torture survivors. Results obtained at Coping scale shows the most frequent coping strategies employed by torture survivors in post war circumstances is asking for social support, especially within female part of sample, which is usual in such conditions. It is obvious that adaptive coping strategies are employed more than non adaptive ones which represent positive and expected treatment outcome. Negative correlation between coping by avoidance and some items at Quality of life scale indicates that as more persons avoid coping with currant difficulties in post war conditions less they have possibilities that using their current resources improve quality of life. At the other hand, positive correlation of some items at Quality of life scale and Distance subscale at Coping scale represent torture survivors currant strength to be engaged in some useful activities, distancing them self's from actual stressors, which is expressed at Quality of life scale results. CONCLUSIONS: According to the results of this study it could be concluded that torture survivors after completed multidisciplinary rehabilitation treatment express: * Moderate satisfaction with the life generally, especially in the fields of life which are not directly connected with complex circumstances of the posttraumatic environment. * Clear need for longer duration of multidisciplinary rehabilitation treatment regarding the results which are related to satisfaction with physical and mental health. * Using more adaptive coping strategies than those directed to emotions, indicated increased relying upon own resources. * The obtained results could be used as the outcome measure after six months duration of multidisciplinary treatment.