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.

Post-traumatic stress disorder (PTSD) is a common and debilitating disorder. The risk of PTSD following trauma is heritable, but robust common variants have yet to be identified by genome-wide association studies (GWAS). We have collected a multi-ethnic cohort including over 30,000 PTSD cases and 170,000 controls. We first demonstrate significant genetic correlations across 60 PTSD cohorts to evaluate the comparability of these phenotypically heterogeneous studies. In this largest GWAS meta-analysis of PTSD to date we identify a total of 6 genome-wide significant loci, 4 in European and 2 in African-ancestry analyses. Follow-up analyses incorporated local ancestry and sex-specific effects, and functional studies. Along with other novel genes, a non-coding RNA (ncRNA) and a Parkinson’s Disease gene, PARK2, were associated with PTSD. Consistent with previous reports, SNP-based heritability estimates for PTSD range between 10-20%. Despite a significant shared liability between PTSD and major depressive disorder, we show evidence that some of our loci may be specific to PTSD. These results demonstrate the role of genetic variation contributing to the biology of differential risk for PTSD and the necessity of expanding GWAS beyond European ancestry.

Abstract 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.

Introduction: Research indicates that women victims of domestic violence show significant cognitive changes, emotional numbing, and avoidance of interpersonal relationships. Aim: The aim of this research was to analyze emotional profile of women victims of domestic violence, and to determine the relationship between dimensions of emotions and frequency of women exposure to domestic violence. Methods: The research was conducted on the sample of 169 women, 111 were victims of domestic violence and 58 were women who did not experience domestic violence. Plutchik’s Emotions Profile Index (EPI) was used for measuring of the emotion profile, and the Modified Inventory of Domestic Violence for measuring experiences of different types of violence. Basic socio-demographic data were also collected. Results: Significant differences between women victims of domestic violence and women who did not experience domestic violence were found in a few dimensions of emotional profile. Women victims of domestic violence had higher results in the dimensions of deprivation/depression and aggression/destruction, while women who did not experience domestic violence had higher results in dimensions of reproduction and incorporation. Aggression was in significant negative correlation with reproduction, incorporation and self protection, whereas it was significant positive correlation with deprivation and opposition. There were significant and positive correlation between the dimensions of aggression and deprivation and frequency of all three forms of domestic violence and age of women. Conclusion: According to results obtained in this research, it can be concluded that women victims of domestic violence have significantly more intensive negative emotional dimensions in comparison to women who were not abused. Women victims of domestic violence with higher frequency of abuse describe themselves as more sad, apathetic, lonely, angry, quarrelsome and less sociable. Prominence of negative emotions, deprivation and aggression, can be factor of risk for mental health disorders and for re-victimisation of women victims of domestic violence.

Introduction: Behavioral problems and emotional difficulties at children of the veterans of war with post-traumatic stress disorder (PTSD) have not been researched entirely. In our country, which has a lot of persons suffering from some psychological traumas, this trauma seems to continue. Aim: The aim of this study was to determine the exposure, manifestations of behavioral problems and emotional difficulties at children and early adolescents, whose fathers were the veterans of war demonstrating post-traumatic stress disorder symptoms. Respondents and methods: The analyzed group comprised 120 school age children (10-15 years of age), whose parents/fathers were the veterans of war. The children were divided into two groups, and each group into the following two age sub-groups: 10-12 (children) and 13-15 (early adolescents) according to PTSD presence at their fathers – veterans of war. PTSD symptoms at fathers, veterans of war, were assessed using the Harvard Trauma Questionnaire–Bosnia and Herzegovina version and MKB-10 – audit of criteria. To assess the behavioral problems of children, the Child Behavior Checklist for parents was used, and to evaluate the neuroticism at children Hanes–Scale of neuroticism-extraversion was used while the depression level was evaluated using the Depression self-rating scale (DSRS). To analyze the obtained results, SPSS 17 program was used. The value p <0. 05 is considered significant. Results: Children of fathers, the veterans of war, demonstrating the PTSD symptoms show more problems in activity, social and school conduct as well as in symptoms of behavioral problems compared to the children whose fathers do not demonstrate the PTSD symptoms (p<0. 001). Children of the war veterans demonstrating the symptoms of the post-traumatic stress disorder show significant difference at neuroticism sub-scales (p<0.001). Negative correlation between PTSD and activity, social and school conduct has been determined (p <0. 01), while positive correlation was determined between PTSD of war veterans with symptoms and neuroticism at children (p <0. 01). Depression symptoms are found at 17.5% children, while 28.3% are in the risky group and the girls demonstrate higher depression level. Conclusion: Children and early adolescents of fathers – veterans of war with post-traumatic stress disorder show significant differences in competencies, behavior, emotional difficulties and neuroticism. Significant correlation was found between psychopathology of parents – fathers the veterans of war and their children. Impact of psychological conditions of fathers – the veterans of war with post-traumatic stress disorder to children is strong and they represent a significant risky group for development of mental disorders.