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.

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.

Aim To analyse symptoms of posttraumatic stress disorder and coping strategies of war veterans in Tuzla Canton twenty years after the war in Bosnia and Herzegovina (BiH). Methods The study analysed a group of 120 war veterans from the Tuzla Canton who had experience of the war in BiH. For assessment of posttraumatic stress disorder Harvard Trauma Questionnaire was used, a version for Bosnia and Herzegovina and for assessment of coping styles Life Style Index was used. Results Concerning number of traumatic experiences of war veterans, it was found that they suffered 12 traumatic experiences. Most often traumatic experience was the participation in fighting and shelling (90.0%), knowledge of injuries in combat or landmine injuries of family members or friends (75.8%), exposure to snipers (74.2%). The most important were the symptoms of numbnessemotional numbness (2.62%), the symptoms of intrusion (2.58%) and the severity of the symptoms of PTSD (2.39%). The most common strategy of dealing with veterans of war was a projection (68.31%) and intellectualisation (56.20%). Conclusion War veterans have experienced polytraumatic experiences in war and show increased expression of symptoms of posttraumatic stress disorder, emphasised psychosocial problems with a common defence mechanism in the form of projections twenty years after the war. War veterans are in need of continuous treatment in order to reduce long-term consequences of war trauma.

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.

Aim To examine how the experience of genocide in Srebrenica in the early childhood (ages 1-5) influences the psychological health in adolescence. Methods This study included 100 school-attending adolescents, age 15-16 (born in 1990-91) who were divided in two groups according to the place of residence from 1992-1995: the Srebrenica group – adolescents who lived in Srebrenica during the siege and the non-Srebrenica group who lived in the “free territory,” were not wounded, and experienced no losses. We used the socio-demographic questionnaire created for the purposes of our study and the War Trauma Questionnaire, Posttraumatic Stress Reactions Questionnaire, Self-report Depressive Scale (Zung), Freiburg Personality Inventory, and the Lifestyle Questionnaire. Results Srebrenica adolescents experienced significantly more traumatic experiences (14.26 ± 3.11 vs 4.86 ± 3.16, P < 0.001). Although there was no significant difference in the total score of posttraumatic stress reactions and intensity of depression between the two groups, significantly higher scores of posttraumatic stress reaction were noticed for several specific questions. The most prominent defense mechanisms in both groups were projection, intellectualization, and reactive formation. Srebrenica adolescents had higher sociability levels (34.7% vs 16.0%, χ2 = 7.231, P = 0.020). Conclusion Srebrenica adolescents reported significantly more severe PTSD symptoms and significantly greater sociability. Our findings could be used for planning treatment and improving communication and overcoming traumas in war-affected areas.