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.

Guidelines for Editing Biomedical Journals: Recommended by Academy of Medical Sciences of Bosnia and Herzegovina.

BACKGROUND: Enormous number of medical journals published around the globe requires standardization of editing practice. OBJECTIVE: The aim of this article was to enlist main principles of editing biomedical scientific journals adopted at annual meeting of Academy of Medical Sciences of Bosnia & Herzegovina (AMSB&H). METHODS: The evidence for writing this Guideline was systematically searched for during September 2020 in the PUBMED and GOOGLE SCHOLAR databases. The inclusion criteria were: original studies, systematic reviews, invited expert opinions, guidelines and editorials. The exclusion criteria were narrative reviews and uninvited opinion articles. The retrieved evidence was analyzed by members of the AMSB&H, then discussed at 2020 annual meeting of the AMSB&H and adopted by nominal group technique. RESULTS: In total 14 recommendations were made, based on A to C class of evidence. The editors should educate potential authors and instruct them how to structure their manuscript, how to write every segment of the manuscript, and take care about correct use of statistical tests. Plagiarism detection softwares should be used regularly, and statistical and technical editing should be rigorous and thorough. International standards of reporting specific types of studies should be followed, and principles of ethical and responsible behavior of editors, reviewers and authors should be published on the journal's web site. The editors should insist on registration of clinical studies before submission, and check whether non-essential personal information is removed from the articles; when essential personal information has to be included, an article should not be published without signed informed consent by the patient to whom these information relate. CONCLUSIONS: Principles of editing biomedical scientific journals recommended in this guideline should serve as one of the means of improving medical journals' quality.

Balkan Clinical Research Registry: Established by Academy of Medical Sciences of Bosnia and Herzegovina.

BACKGROUND: From 2013 the World Medical Association's Declaration of Helsinki explicitly requires pre-registration of a study involving human subjects. The registration gives a chance for improvement of design and avoidance of bias. OBJECTIVE: The aim of this article was to describe process of bearing decision to create regional registry of clinical studies for Balkan countries. METHODS: After finding relevant studies about research registries and designing the concept and structure of future regional registry an article was published in IJBH journal. The article was than used as basis for discussion at 2020 meeting of Academy of Medical Sciences of Bosnia and Herzegovina (AMSBH), and final decision was made by the Academy to create the research registry. RESULTS: Regional registry of clinical studies will be under the auspices of AMSBH and web-based, with the option of online registration of new studies. The data required to be entered in the moment of registration relate to key elements of research plan: topic, variables, sample, type of the study and the study population. After applying for registration of a clinical study, the authors will soon receive the review made by the AMSBH expert committee. The application could be accepted, rejected or returned for major or minor revision. After an application is accepted, it will be deposited in the searchable database and given the registration number. CONCLUSION: The AMSBH's decision to create the regional registry of clinical studies will satisfy needs of researchers from Balkan countries in the first place, who share cultural and lingual similarities. It will also help with increasing standards of clinical research in the region.

Association Analysis of Maoa and Slc6a4 Gene Variation in South East European War Related Posttraumatic Stress Disorder.

BACKGROUND: The aim of this study is to investigate the association of gene variations of the monoamine oxidase A (MAOA) and the serotonin transporter solute carrier family 6 member 4 (SLC6A4) gene with posttraumatic stress disorder (PTSD) severity and coping strategies in patients with war related PTSD. SUBJECTS AND METHODS: The study included 747 individuals who had experienced war trauma in the South Eastern Europe conflicts between 1991 and 1999. Genotyping of the MAOA VNTR and SLC6A4 tandem repeat polymorphism in combination with rs25531 was done in 719 participants: 232 females and 487 males. Among them, 369 have had current or lifetime PTSD and 350 have had no PTSD symptoms. For psychometric approach we used the Clinician Administrated PTSD Scale (CAPS), the Brief Symptom Inventory (BSI), the adapted Hoffman-Lazarus Coping scale and a basic socio-demographic data questionnaire. RESULTS: There were no significant intergroup (PTSD versus non PTSD) differences in the genotype distribution of MAOA and SLC6A4 gene polymorphisms. The primary finding of our study was that the MAOA short allele (MAOA-S) was nominally significantly associated with the severity of PTSD symptoms in the total subgroup of participants with lifetime PTSD; males for symptoms of hyperarrousal and females with symptoms of re-experience and hyperarousal. In our research the male subsample with current PTSD and MAOA-S genotype had nominally significantly higher scores for some positive coping strategies compared to those carrying the long allele genotype (MAOA-L). There was no significant association between the severity of PTSD symptoms, BSI phenotype, coping scores and the SLC6A4 genotype. CONCLUSION: The present results support the notion that MAOA VNTR gene variation modulates development and recovery of posttraumatic stress disorder in a war traumatised population, but did not support a connection between SLC6A4 gene variations and war related PTSD.

Genetic Susceptibility to Posttraumatic Stress Disorder: Analyses of the Oxytocin Receptor, Retinoic Acid Receptor-Related Orphan Receptor A and Cannabinoid Receptor 1 Genes.

BACKGROUND: Exposure to life-threatening events is common and everyone will most likely experience this type of trauma during their lifetime. Reactions to these events are highly heterogeneous and seems to be influenced by genes as well. Some individuals will develop posttraumatic stress disorder (PTSD), while others will not. In this study, our aim was to analyze the correlation between single nucleotide polymorphisms (SNPs) within the oxytocin receptor (OXTR) gene (rs53576 and rs2254298), the RAR-related orphan receptor A (RORA) gene (rs8042149) and the cannabinoid receptor 1 (CNR1) gene (rs1049353) and PTSD. All candidate genes have been previously associated with stress related disorders and the reaction to traumatic events. SUBJECTS AND METHODS: Participants (N=719) have been exposed to war-related trauma during the war in South-Eastern Europe (Bosnia and Herzegovina, Croatia and Kosovo). We correlated the presence and absence of current and lifetime PTSD as well as PTSD severity (Clinician Administered PTSD scale (CAPS)) and current psychopathology (Brief Symptom Inventory (BSI) score) with the mentioned SNPs. DNA was isolated from whole blood and genotyped for OXTR rs2254298 and rs53576 following previously published protocols, for RORA rs8042149 via PCR-RFLP and CNR1 rs1049353 via KASP. RESULTS: Nominally significant results were found for OXTR rs53576 in connection with the CAPS and BSI scores within lifetime PTSD patients. The additive allelic model indicated that G allele carriers achieved lower CAPS (p=0.0090) and BSI (p=0.0408) scores than participants carrying one or two copies of the A allele. These results did not withstand correction for multiple tests. No significant results were observed for OXTR rs2254298, RORA rs8042149 and CNR1 rs1049353 although the results for RORA showed a slight tendency that rs8042149 may influence the level of BSI scores in current PTSD patients. CONCLUSIONS: This study points to a role of the OXTR gene in PTSD and the related psychopathology following war related trauma.

Associations between Polymorphisms in the Solute Carrier Family 6 Member 3 and the Myelin Basic Protein Gene and Posttraumatic Stress Disorder.

BACKGROUND: Previous research showed inconsistent results concerning a possible association between solute carrier family 6 member 3 (SLC6A3) gene polymorphisms and dopamine symptoms of posttraumatic stress disorder (PTSD). Several studies also indicate that the myelin basic protein (MBP) gene is of importance in the etiology of several psychiatric disorders. The aim of this study was to investigate the relation of distinct SLC6A3 and MBP gene polymorphisms with PTSD and whether SLC6A3 and MBP genotypes contribute to PTSD symptom severity. SUBJECTS AND METHODS: The study included 719 individuals who had experienced war trauma in the South Eastern Europe (SEE). Genotypes of variable number tandem repeat (VNTR) polymorphism within the SLC6A3 gene were assessed in 696 participants, and the single nucleotide polymorphism (SNP) rs12458282 located within the MBP gene region was genotyped in a total of 703 subjects. The Mini International Neuropsychiatric Interview, the Clinical Administrated PTSD Scale (CAPS) and Brief Symptom Inventory (BSI), were used for data collection. RESULTS: No significant differences concerning the investigated SLC6A3 and MBP polymorphisms was identifiable between PTSD and non PTSD participants. Also we could not detect significant influence of these distinct SLC6A3 and MBP alleles on the severity of PTSD symptoms (CAPS) or BSI scores. However, the results of MBP rs12458282 within the patients with lifetime PTSD may point to a possible correlation of the major allele (T) with elevated CAPS scores. CONCLUSIONS: Our results do not support an association of the analysed SLC6A3 and MBP gene polymorphisms with PTSD in war traumatized individuals. We found that there is a possibility for a correlation of the T allele rs12458282 within the MBP gene with higher CAPS scores in lifetime PTSD patients which would need to be tested in a sample providing more statistical power.

Associations of Gene Variations in Neuropeptide Y and Brain Derived Neurotrophic Factor Genes with Posttraumatic Stress Disorder.

BACKGROUND: Individuals who are exposed to traumatic events are at an increased risk of developing posttraumatic stress disorder (PTSD), a condition during which an individual's ability to function is impaired by emotional responses to memories of those events. The gene coding for neuropeptide Y (NPY) and the gene coding for brain-derived neurotrophic factor (BDNF) are among the number of candidate gene variants that have been identified as potential contributors to PTSD. The aim of this study was to investigate the association between NPY and BDNF and PTSD in individuals who experienced war-related trauma in the South Eastern Europe (SEE) conflicts (1991-1999). SUBJECTS AND METHODS: This study included participants with current and remitted PTSD and healthy volunteers (N=719, 232 females, 487 males), who were recruited between 2013 and 2015 within the framework of the South Eastern Europe (SEE) - PTSD Study. Psychometric methods comprised the Mini International Neuropsychiatric Interview (M.I.N.I.), the Clinician Administered PTSD Scale (CAPS), and the Brief Symptom Inventory (BSI). DNA was isolated from whole blood and genotyped for NPY rs5574 via PCR - RFLP and NPY rs16147 and BDNF rs6265 using the KASP assay. RESULTS: Tests for deviation from Hardy-Weinberg equilibrium showed no significant results. Analyses at the categorical level yielded no associations between the affected individuals and all three SNPs when compared to controls. Within lifetime PTSD patients, the major alleles of both NPY variants showed a nominally significant association with higher CAPS scores (p=0.007 and p=0.02, respectively). Also, the major allele of rs5574C>T was associated with higher BSI scores with a nominal significance among current PTSD patients (p=0.047). The results did not withstand a Bonferroni adjustment (α=0.002). CONCLUSION: Nominally significant associations between NPY polymorphisms and PTSD susceptibility were found that did not withstand Bonferroni correction.

The Association of Catechol-O-Methyl-Transferase and Interleukin 6 Gene Polymorphisms with Posttraumatic Stress Disorder.

BACKGROUND: Posttraumatic stress disorder (PTSD) is a disorder that occurs in some people who have experienced a severe traumatic event. Several genetic studies suggest that gene encoding proteins of catechol-O-methyl-transferase (COMT) may be relevant for the pathogenesis of PTSD. Some researchers suggested that the elevation of interleukin-6 (IL6) correlates with major depression and PTSD. The aim of this study was to investigate whether the single nucleotide polymorphisms COMT rs4680 (Val158Met) and IL6 rs1800795 are associated with PTSD and contribute to the severity of PTSD symptoms. SUBJECTS AND METHODS: This study comprised 747 participants that experienced war between 1991 and 1999 in the South Eastern Europe conflicts. COMT rs4680 (Val158Met) and IL6 rs1800795 genotypes were determined in 719 participants (369 with and 350 without PTSD). The Mini International Neuropsychiatric Interview (M.I.N.I.), the Clinician Administrated PTSD Scale (CAPS) questionnaire and the Brief Symptom Inventory (BSI) were used for data collection. RESULTS: Regarding the COMT gene polymorphism, the results of the regression analyses for BSI total score were significant in the lifetime PTSD group in the dominant (P=0.031) and the additive allelic model (P=0.047). Regarding the IL6 gene, a significant difference was found for the recessive model predicting CAPS total score in the lifetime PTSD group (P=0.048), and indicated an association between the C allele and higher CAPS scores. n the allelic, genotypic and rezessive model, the results for BSI total score were significant in the lifetime PTSD group (P=0.033, P=0.028 and P=0.009), suggesting a correlation of the C allele with higher BSI scores. CONCLUSION: Although our nominally significant results did not withstand correction for multiple tests they may support a relevance of the COMT (Val158Met) and IL6 rs1800795 polymorphism for aspects of PTSD in war traumatized individuals.

Association of Neuropeptide S Receptor 1 and Glutamate Decarboxylase 1 Gene Polymorphisms with Posttraumatic Stress Disorder.

BACKGROUND: Posttraumatic stress disorder (PTSD) is an anxiety disorder caused by highly traumatic experiences. The aim of this study was to investigate the influence of single nucleotide polymorphisms (SNPs) in the neuropeptide S receptor 1 (NPSR1) and the glutamate decarboxylase 1(GAD1) gene on PTSD and its psychopathological aspects among individuals affected by the Balkan wars during the 90s. SUBJECTS AND METHODS: This study was conducted as part of the South Eastern Europe (SEE) study on molecular mechanisms of PTSD. It comprised 719 participants (539 males), including those with current PTSD, remitted PTSD and healthy volunteers. Psychometric evaluation was performed using the Mini International Neuropsychiatric Interview (M.I.N.I.), the Clinician Administrated PTSD Scale (CAPS) andthe Brief Symptom Inventory (BSI). We examined NPSR1 single nucleotide polymorphism (SNP) rs324981 and GAD1 variant rs3749034 genotypes. Case-control analyses were carried out using logistical regression to determine genotype differences between all patients that had either current or remitted PTSD and control individuals. To analyse the influence of the analysed SNPs on PTSD severity, we performed linear regression analyses with CAPS and BSI within each of the two patient groups separately. All of the calculations were performed for additive allelic, recessive, dominant and genotypic models. RESULTS: We observed a nominally significant association for the major allele (G) of GAD1 rs3749034 with an increased risk to develop PTSD in a case control analysis in the recessive model (P=0.0315, odds ratio=0.47, SE=0.35). In contrast, a nominally significant association of the minor allele (A) with higher CAPS scores was identified within the patient group with lifetime PTSD in the dominant model (P=0.0372, ß=6.29, SE=2.99). None of these results did withstand correction for multiple tests. No nominal significant results of GAD1 rs3749034 were found with regard to the intensity of psychological BSI symptoms. Case-control analyses of NPSR1 rs324981 revealed a nominally significant higher risk for homozygous T allele carriers to develop PTSD (P=0.0452) in the recessive model. On the other hand, the T allele showed a nominally significant association with higher BSI scores in patients suffering from lifetime PTSD in the recessive model (P=0.0434). Again, these results were not significant anymore after correction for multiple tests. No associations of NPSR1 rs324981 and CAPS score was identified. CONCLUSION: The findings of this study provide some evidence that the NPSR1 and GAD1 polymorphisms might play a role in the development of war-related PTSD and its related psychological expressions. Further research is needed to elucidate the interactions of specific gene variants and environmental factors in the development of PTSD.

Role of the Allelic Variation in the 5-Hydroxytryptamine Receptor 1A (HTR1A) and the Tryptophan Hydroxylase 2 (TPH2) Genes in the Development of PTSD.

BACKGROUND: Post-traumatic stress disorder (PTSD) is a stress related disorder which can occur in an individual after exposure to a traumatic event. It most commonly co-occurs with depression. The two disorders share not only overlapping symptoms, but also genetic diathesis. The aim of this study was to investigate the potential role of single nucleotide polymorphisms (SNPs) of the two serotonergic candidate genes 5-hydroxytryptamine receptor 1A (HTR1A) and tryptophan hydroxylase 2 (TPH2) in the pathogenesis of PTSD and comorbid psychopathology. SUBJECTS AND METHODS: 719 (487 males, 232 females) participants who had experienced war-related trauma between 1991 and 1999 in Bosnia and Herzegovina, Kosovo and Croatia were included in the study. The Sociodemographic questionnaire, Mini International Neuropsychiatric Interview (M.I.N.I.), Clinician Administered PTSD Scale (CAPS) and Brief Symptom Inventory (BSI) were used to collect clinical data. The SNPs rs6295 (HTR1A), rs11178997 and rs1386494 (TPH2) were investigated for their association with PTSD and comorbid psychopathology. RESULTS: A nominal significant association was found between the BSI total score in Lifetime PTSD with the SNP rs6295 of the HTR1A gene. The best result was seen in the dominant model (P=0.018), with the minor allele (C) being the risk allele. Several BSI subscores were also associated with the minor (C) allele in Lifetime PTSD. No association was found for the TPH2 SNPs rs11178997 and rs1386494 in relation to PTSD or comorbid psychopathology. CONCLUSIONS: Our findings suggest that rs6295 in the HTR1A gene may contribute to the psychopathology of PTSD.

The Role of TaqI DRD2 (rs1800497) and DRD4 VNTR Polymorphisms in Posttraumatic Stress Disorder (PTSD).

BACKGROUND: Posttraumatic stress disorder (PTSD) is a complex stress related disorder, that follows a severe traumatic experience, characterized with an intense sense of terror, fear, and helplessness. The aim of this study is to identify associations of genetic variations within candidate genes DRD2 and DRD4 with various PTSD related phenotypes. PTSD lifetime and PTSD current subjects were analyzed separately, each of them were analyzed in a Case/Control design, as well as regarding BSI and CAPS within cases only. SUBJECTS AND METHODS: 719 (487 male, 232 female) participants who had experienced war-related trauma between 1991 and 1999 in Bosnia and Hercegovina, Kosovo and Croatia were included in the study. Sociodemographic questionnaire, Clinician Administered PTSD Scale (CAPS) and the Brief Symptom Inventory (BSI) were used to collect clinical data. RESULTS: The DRD2 rs1800497 variant and a variable number tandem repeat (VNTR) located in exon three of DRD4 were investigated for association with PTSD. In case control analyses we did not identify any significant associations. Within the PTSD current patients, we identified an association of DRD2 rs1800497 with BSI in the genotypic and the recessive model with the T allele as the risk allele. CONCLUSION: Our findings suggest that rs1800497 of DRD2 gene is involved in pathogenesis of PTSD.

A Candidate Gene Association Study of FKBP5 and CRHR1 Polymorphisms in Relation to War-Related Posttraumatic Stress Disorder.

BACKGROUND: Posttraumatic stress disorder (PTSD) is a highly frequent and disabling psychiatric condition among war-affected populations. The FK506-binding protein 5 (FKBP5) gene and the corticotropin-releasing hormone receptor 1 (CRHR1) gene have previously been implicated in an elevated risk of peritraumatic dissociation and PTSD development. Our aim was to investigate the association between FKBP5 and CRHR1 genotypes and PTSD diagnosis and severity among individuals who were affected by the Balkan wars during the 1990s. SUBJECTS AND METHODS: This study included participants with current PTSD, remitted PTSD and healthy volunteers (N=719, 487 males), who were recruited between 2013 and 2015 within the framework of the South Eastern Europe (SEE) - PTSD Study. Psychometric methods comprised the Mini International Neuropsychiatric Interview (M.I.N.I.), the Clinician Administrated PTSD Scale (CAPS), and the Brief Symptom Inventory (BSI). FKBP5 rs1360780 and CRHR1 rs17689918 genotypes were determined using a KASP genotyping assay. RESULTS: Tests for deviation from Hardy Weinberg equilibrium showed no significant results. Logistic and linear regression was used to examine the associations between the FKBP5 SNP rs1360780 and the CRHR1 SNP rs17689918 with PTSD diagnosis and severity, as well as general psychiatric symptom severity, separately for current and remitted PTSD patients. There were nominally significant associations under a dominant model between the rs1360780 C allele and PTSD diagnosis as well as symptom severity, which however, were not significant anymore after Bonferroni adjustment (α=0.002). For CRHR1 rs17689918 no significant associations were detected. CONCLUSION: We found nominally, but not Bonferroni corrected significant associations between the FKBP5 polymorphism rs1360780 and PTSD susceptibility among individuals affected by the Balkan wars. For elucidating this gene's real resilience/vulnerability potential, environmental influences should be taken into account.

Monoamine Oxidase A Gene Methylation and Its Role in Posttraumatic Stress Disorder: First Evidence from the South Eastern Europe (SEE)-PTSD Study.

Background: Posttraumatic stress disorder is characterized by an overactive noradrenergic system conferring core posttraumatic stress disorder symptoms such as hyperarousal and reexperiencing. Monoamine oxidase A is one of the key enzymes mediating the turnover of noradrenaline. Here, DNA methylation of the monoamine oxidase A gene exonI/intronI region was investigated for the first time regarding its role in posttraumatic stress disorder risk and severity. Methods: Monoamine oxidase A methylation was analyzed via direct sequencing of sodium bisulfite-treated DNA extracted from blood cells in a total sample of N=652 (441 male) patients with current posttraumatic stress disorder, patients with remitted posttraumatic stress disorder, and healthy probands (comparison group) recruited at 5 centers in Bosnia-Herzegovina, Croatia, and the Republic of Kosovo. Posttraumatic stress disorder severity was measured by means of the Clinician-Administered Posttraumatic Stress Disorder Scale and its respective subscores representing distinct symptom clusters. Results: In the male, but not the female sample, patients with current posttraumatic stress disorder displayed hypermethylation of 3 CpGs (CpG3=43656362; CpG12=43656514; CpG13=43656553, GRCh38.p2 Assembly) as compared with remitted Posttraumatic Stress Disorder patients and healthy probands. Symptom severity (Clinician-Administered Posttraumatic Stress Disorder Scale scores) in male patients with current posttraumatic stress disorder significantly correlated with monoamine oxidase A methylation. This applied particularly to symptom clusters related to reexperiencing of trauma (cluster B) and hyperarousal (cluster D). Conclusions: The present findings suggest monoamine oxidase A gene hypermethylation, potentially resulting in enhanced noradrenergic signalling, as a disease status and severity marker of current posttraumatic stress disorder in males. If replicated, monoamine oxidase A hypermethylation might serve as a surrogate marker of a hyperadrenergic subtype of posttraumatic stress disorder guiding personalized treatment decisions on the use of antiadrenergic agents.

Stigma and Suicide.

Suicide is one of the major mental health problems in the world. It is estimated that one million suicide are committed per year and that after every suicide six people from the surrounding suffer or develop major life changes. After suicide survivors are at higher risk of developing major psychological changes and suicidal ideations as well. They go through the complicated process of grief which is specifically characterized by the felling of guilt, shame, denial and anger. The griefing process, more often than in other causes of death, doesn't integrate but is complicated with prolonged grief. This represents a very favorable state for perceiving stigma. Stigma is most often defined as a mark of disgrace or infamy; a stain or reproach, as on one's reputation. In suicide we talk about public and self stigma. Both forms of stigma can separately cause social isolation, demoralization, the felling of hopelessness and other consequences that interfere with the previous functioning. Because of the high incidence of psychological changes after stigma it is crucial for the bereaved to have close mental health services. But stigma is a barrier to treatment seeking. After suicide most survivors fell stigmatized but it is not yet known which factors modify the perception of stigma. Other causes of death like natural death are less related to stigma. On the other side traumatic death like an accident or homicide seem to be related to perception of stigma in the same way survivors perceive after suicide. Suicide and stigma are related in a two way direction meaning that suicide can cause stigma but stigma can lead to suicidal thoughts as well. Even suicide attempters fell stigmatized by colleagues, medical staff and their closest surrounding. There is a need for interventions. The effect of broad anti-stigma campaigns and targeted programs still have to be examines. In clinical settings, interventions that reduce self stigma, stigma-stress and shame might successfully reduce suicidality.

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.

Fatigue during multiple sclerosis relapse and its relationship to depression and neurological disability.

BACKGROUND: Fatigue is a common symptom of multiple sclerosis patients that may be present at all stages of the disease. The aim of this study was to determine presence of fatigue in multiple sclerosis patients during relapse and its relation to neurological disability and depression. SUBJECTS AND METHODS: This cross-sectional study included 120 patients who were assessed during the acute relapse of relapsing-remitting multiple sclerosis. Applied research instruments were: general questionnaire, Expanded Disability Status Scale (EDSS), Beck Depression Inventory-II (BDI-II) and Fatigue Severity Scale (FSS). All patients were examined at the same appointment. RESULTS: 54 (45%) patients were grouped into MS fatigue (MSF) group (FSS≥5) and 48 (40%) as non-fatigue (MSNF) group (FSS≤4). Mean FSS score was 4.83+/-1.49. Difference between MSF and MSNF patients was significant considering age (p<0.001), relapse severity (p=0.044), BDI score (p<0.001) and EDSS score (p<0.001). Positive correlations of fatigue (FSS) with age (rho=0.41, p<0.001), depression (BDI score) (rho=0.61, p<0.001) and neurological disability (EDSS score) (rho=0.55, p<0.001) were confirmed. After adjusting for depression, there was only weak positive correlation between fatigue and neurological disability (rs=0.38; P<0.001), while after adjusting for EDSS score, fatigue continued to correlate moderately with depression (r=0.48; p<0.001). Multiple linear regression analysis showed that BDI score (beta=0.380; p<0.001), EDSS score (beta=0.336, p<0.001) and the age (beta=0.202; p<0.05) are independently related to fatigue severity in this patients. CONCLUSION: Fatigue is a frequent symptom during multiple sclerosis relapse. Depression and, to a lesser degree, disability but not relapse severity are independently related to the presence of fatigue. Depression and fatigue should be recognized and treated during standard relapse treatment. Further research might focus on other factors influencing fatigue during multiple sclerosis relapse including evaluation of fatigue at the different time points.

Recovery from posttraumatic stress symptoms: a qualitative study of attributions in survivors of war.

OBJECTIVE: The study explored factors to which people traumatized by war attribute their recovery from posttraumatic symptoms and from war experiences. METHODS: In-depth interviews were conducted with two groups of participants with mental sequelae of the war in the former Yugoslavia: 26 people who had recovered from posttraumatic stress disorder (PTSD) and 17 people with ongoing symptoms of PTSD. Participants could attribute their recovery to any event, person or process in their life. The material was subjected to thematic analysis. RESULTS: Eight themes covered all factors to which participants attributed their recovery. Six themes described healing factors relevant for both groups of participants: social attachment and support, various strategies of coping with symptoms, personality hardiness, mental health treatment, received material support, and normalization of everyday life. In addition to the common factors, recovered participants reported community involvement as healing, and recovered refugees identified also feeling safe after resolving their civil status as helpful. Unique to the recovered group was that they maintained reciprocal relations in social attachment and support, employed future-oriented coping and emphasised their resilient personality style. CONCLUSIONS: The reported factors of recovery are largely consistent with models of mental health protection, models of resilience and recommended interventions in the aftermath of massive trauma. Yet, they add the importance of a strong orientation towards the future, a reciprocity in receiving and giving social support and involvement in meaningful activities that ensure social recognition as a productive and valued individual. The findings can inform psychosocial interventions to facilitate recovery from posttraumatic symptoms of people affected by war and upheaval.

Subjective quality of life in war-affected populations.

BACKGROUND: Exposure to traumatic war events may lead to a reduction in quality of life for many years. Research suggests that these impairments may be associated with posttraumatic stress symptoms; however, wars also have a profound impact on social conditions. Systematic studies utilising subjective quality of life (SQOL) measures are particularly rare and research in post-conflict settings is scarce. Whether social factors independently affect SQOL after war in addition to symptoms has not been explored in large scale studies. METHOD: War-affected community samples were recruited through a random-walk technique in five Balkan countries and through registers and networking in three Western European countries. The interviews were carried out on average 8 years after the war in the Balkans. SQOL was assessed on Manchester Short Assessment of Quality of Life--MANSA. We explored the impact of war events, posttraumatic stress symptoms and post-war environment on SQOL. RESULTS: We interviewed 3313 Balkan residents and 854 refugees in Western Europe. The MANSA mean score was 4.8 (SD = 0.9) for the Balkan sample and 4.7 (SD = 0.9) for refugees. In both samples participants were explicitly dissatisfied with their employment and financial situation. Posttraumatic stress symptoms had a strong negative impact on SQOL. Traumatic war events were directly linked with lower SQOL in Balkan residents. The post-war environment influenced SQOL in both groups: unemployment was associated with lower SQOL and recent contacts with friends with higher SQOL. Experiencing more migration-related stressors was linked to poorer SQOL in refugees. CONCLUSION: Both posttraumatic stress symptoms and aspects of the post-war environment independently influence SQOL in war-affected populations. Aid programmes to improve wellbeing following the traumatic war events should include both treatment of posttraumatic symptoms and social interventions.

The utilization and perceived usefulness of health care and other support services by people exposed to traumatic events related to the war in the Balkans.

OBJECTIVE: To explore which health care and other support services people exposed to traumatic events related to the war use, how helpful they perceive them in the course of their post-war adaptation and whether utilization and perceived usefulness depend on the mental health status of participants. METHODS: A community sample of 3304 adults exposed to at least one war-related traumatic event was randomly selected in different regions in the former Yugoslavia. A specifically designed instrument, the Matrix for the Assessment of Community and Healthcare Services, was used to record service utilization and their perceived usefulness. The mental health status of participants was assessed using the Mini International Neuropsychiatric Interview. RESULTS: Primary health care was the most frequently used type of service (80.5%). Services providing help with leisure activities, social support and social contacts were perceived as most helpful. Participants with current post-traumatic stress disorder used all types of health care services and employment support services significantly more often than participants without mental disorders and participants with other mental disorders. They were more satisfied with primary health care services than participants without mental disorders and less satisfied with financial and material support services as compared to participants with other mental disorders. CONCLUSIONS: The frequency of utilization of different types of services varies greatly in war affected communities. Medical services are widely used and therefore have a central role in the care provision following a war. Services providing help with leisure activities and social support are most appreciated and may be more widely established.

Co-occurrence of major depressive episode and posttraumatic stress disorder among survivors of war: how is it different from either condition alone?

OBJECTIVE: Major depressive episode (MDE) and posttraumatic stress disorder (PTSD) have been shown to be the most common mental disorders following traumatic war experiences and have been found to frequently co-occur. This study, designed as a randomized cross-sectional interview survey, aimed to identify whether the co-occurence of MDE and PTSD following exposure to war-related experiences is associated with different demographics, exposure to previous traumatic events, and clinical characteristics than either condition alone. METHOD: After a random-walk technique was used to randomly select participants, face-to-face interviews were conducted among war-affected community samples in 5 Balkan countries (N = 3,313) in the years 2006 and 2007. The mean age of participants was 42.3 years, and all participants had experienced potentially traumatic events during war in the countries of the former Yugoslavia. Current prevalence rates of MDE and PTSD and suicide risk were assessed using the Mini-International Neuropsychiatric Interview. Levels of general psychological distress, posttraumatic stress, and quality of life were assessed with self-reports. RESULTS: 30.5% of the sample met DSM-IV diagnostic criteria for either MDE or PTSD, and 9.1% had both disorders. Participants with concomitant MDE and PTSD reported significantly higher numbers of prewar and postwar traumatic events than participants with PTSD only and higher numbers of war-related events than those with MDE only (all P values < .001). Participants with both MDE and PTSD had significantly higher levels of general psychological and posttraumatic stress symptoms, a higher suicide risk, and lower levels of quality of life than participants with either condition alone (all P values < .001). CONCLUSIONS: Concomitant MDE and PTSD are associated with the experience of different traumatic events and are characterized by more general psychological distress than either condition alone. The assessment of concomitant MDE and PTSD can facilitate better identification of individuals with severe psychopathology and poor quality of life. People with co-occurrence of MDE and PTSD may require specific health care programs following war.