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I. Pajević, M. Hasanovic, E. Avdibegović, A. Dzubur-Kulenovic, M. Burgic-Radmanovic, D. Babic, N. Mehić-Basara, N. Zivlak-Radulovic et al.

Background: Coronavirus disease 2019 (COVID-19), like any other pandemic, has imposed an unprecedented threat to physical and mental health to all nations, worldwide. There is no enough evidence in the literature in this area. The present study has been done to explore the organization of psychiatric services in Bosnia and Herzegovina (BH) to meet mental health needs of BH citizens during the particular restrictive measures caused by COVID-19 pandemic. Materials and Methods: This online survey has been done for BH psychiatric institutions. Data were collected from psychiatric institutions in the mental health network of BH. A total of 38 complete responses have been received. Results: Of 38 study participants, three were the departments of psychiatry in university clinical centers, two were psychiatric hospitals, four were psychiatric wards in general hospitals, 27 were community mental health centers, and two were institutes for alcoholism and drug addiction. During the pandemic, all services functioned on a reduced scale, adhering to measures to protect and self-protect both staff and service users. Protective equipment was provided to staff in some institutions in a timely and complete manner and in some in an untimely and incomplete manner. Consultative psychiatric examinations were mainly performed through telephone and online, where it exists as a standard patient monitoring protocol. The application of long-acting antipsychotics was continuous with adherence to restricted and protective measures. In opiate addiction replacement therapy services, substitution therapy was provided for a longer period to reduce frequent contacts between staff and patients. Individual and group psychotherapy continued in reduced number using online technologies, although this type of service was not administratively regulated. An initiative has been given to regulate and administratively recognize telepsychiatry by health insurance funds in the country. A number of psychological problems associated with restrictive measures and fear of illness have been reported by patients as well as by the professionals in mental healthcare teams. There were no COVID-19-positive patients seeking help from institutions that responded to the questionnaire. In one center, infected people with COVID-19 from abroad sought help through the phone. Only one involuntary hospitalization was reported. The involvement of mental health professionals in the work of crisis headquarters during the design of the COVID-19 pandemic control measures varies from satisfactory to insufficient. Education of staff, patients, and citizens was regular with direct instructions through meetings, press, and electronic media. Conclusions: During the COVID-19 pandemic in BH, all psychiatric services functioned on a reduced scale, adhering to measures to protect and self-protect staff and service users. All patients who asked for help have been adequately treated in direct inpatient or outpatient mental healthcare or online, despite telepsychiatric services not being recognized in health system in BH. There were neither infected patients nor staff with COVID-19 in the psychiatric institutions who responded in this research. A large-scale, multicenter study needs to be performed to get a broader picture and to guide us for future better service planning and delivery.

M. Brkić, R. Kovačević, Dženita Hrvić, Z. Selimbašić, E. Avdibegović

Background: People with mental and behavioural disorders have low satisfaction of quality of life, due to numerous symptoms, as well as poor interpersonal relations, communications skills, low tolerance on frustration. Aim: The aim of this paper was to evaluate whether there has been an improvement in satisfaction with the quality of life after the application of group therapy Methods: The study included 100 patients who attended group therapy, for a period of 6-12 weeks. The instruments used at the beginning and at the end of the treatment were Outcome Questionnaire-45 which measured symptoms distress, interpersonal relations, and social roles, and MANSA questionnaire that measured satisfaction with the quality of life. Results: In total sample (N = 100) there was approximately equal number of women and men (51% vs. 49%). The average age of the subjects was 48.11 ± 7.91. Majority of respondents had depressive disorder (45%). Measuring the mean values obtained on the OQ-45 questionnaire, it was found that after the application of group therapy a significant reduction of the level of dysfunction was achieved. A statistically significant difference was found in the areas of satisfaction with physical and mental health, and the overall score of the MANSA questionnaire. Conclusion: Results show that patients reported lower symptoms distress and higher satisfaction with quality of life after attending group therapy, better interpersonal relations, lower risk of suicidal behaviour and substance abuse. Group therapy is successful intervention which helps patients improve quality of life.

Mackenzie J Lind, L. Brick, P. Gehrman, L. Duncan, B. Gelaye, A. Maihofer, C. Nievergelt, N. Nugent et al.

STUDY OBJECTIVES Sleep problems are common, serving as both a predictor and symptom of posttraumatic stress disorder (PTSD), with these bidirectional relationships well established in the literature. While both sleep phenotypes and PTSD are moderately heritable, there has been a paucity of investigation into potential genetic overlap between sleep and PTSD. Here, we estimate genetic correlations between multiple sleep phenotypes (including insomnia symptoms, sleep duration, daytime sleepiness, and chronotype) and PTSD, using results from the largest genome-wide association study (GWAS) to date of PTSD, as well as publicly available GWAS results for sleep phenotypes within UK Biobank data (23 variations, encompassing four main phenotypes). METHODS Genetic correlations were estimated utilizing linkage disequilibrium score regression (LDSC), an approach that uses GWAS summary statistics to compute genetic correlations across traits, and Mendelian randomization (MR) analyses were conducted to follow up on significant correlations. RESULTS Significant, moderate genetic correlations were found between insomnia symptoms (rg range 0.36-0.49), oversleeping (rg range 0.32-0.44), undersleeping (rg range 0.48-0.49), and PTSD. In contrast, there were mixed results for continuous sleep duration and daytime sleepiness phenotypes, and chronotype was not correlated with PTSD. MR analyses did not provide evidence for casual effects of sleep phenotypes on PTSD. CONCLUSION Sleep phenotypes, particularly insomnia symptoms and extremes of sleep duration, have shared genetic etiology with PTSD, but causal relationships were not identified. This highlights the importance of further investigation into the overlapping influences on these phenotypes as sample sizes increase and new methods to investigate directionality and causality become available.

E. Becirovic, E. Avdibegović, R. Softić, M. Mirković Hajdukov

Sexual functioning of war veterans is significantly under-explored. During devastating aggression on Bosnia-Herzegovina (BiH) around 400 thousand soldiers were included in combats. It is estimated that more than 100 000 persons were killed, and more than 60 000 them were soldiers. Vast majority of them were deployed since war is ended. We found high prevalence of sexual dysfunctions in war veterans. Also significant difference in several areas of sexual functioning between war veterans with and without symptoms of posttraumatic stress disorder was found.

C. Nievergelt, A. Maihofer, T. Klengel, Elizabeth G. Atkinson, Chia-Yen Chen, Karmel W. Choi, J. Coleman, S. Dalvie et al.

Kimberley Anderson, I. Komproe, A. Delić, E. Avdibegović, E. V. Ee, H. Glaesmer

Background: Posttraumatic stress disorder (PTSD) and posttraumatic growth (PTG) are known psychological outcomes that can co-occur in the aftermath of a traumatic event. However, it is less clear how these outcomes interact – particularly for female survivors of conflict-related sexual violence (CRSV) – and to what extent intermediary factors play a role in this relationship. Methods: In a sample of 192 war survivors from Bosnia & Herzegovina (n = 104 experienced CRSV, n = 88 did not), a structural equation model (LISREL 8.8) tested CRSV as a traumatic event, 'positive reinterpretation' (as a strategy of approach coping) and 'behavioural disengagement' (as a strategy of avoidance coping), and PTSD and PTG as psychosocial outcomes. A difference in the mechanisms by which PTG and PTSD interact in the two subgroups was hypothesised, given the differences in the nature of the trauma they experienced. Results: Through multiple indirect relationships, results showed that CRSV survivors respond to their trauma with both PTSD and PTG, suggesting a dual PTSDPTG mechanism. As for coping strategies, positive reinterpretation predicted greater PTG, and behavioural disengagement predicted greater PTSD. In the sample of nonsexual violence survivors, positive reinterpretation also remained a significant predictor of PTG. Conclusions: Positive reinterpretation as a coping strategy appears to be a stable characteristic that independently predicts PTG, irrespective of trauma type. Mental health professionals should take into account this mechanism when addressing the needs of CRSV survivors, but also war survivors more generally. Reframing traumatic events and post-trauma sequalae during treatment could lead to PTG and enhance recovery.

N. Kravić, Emina Šabić Džananović, Mirnesa Muminović Umihanić, A. Džubur Kulenović, O. Sinanović, M. Jakovljevič, D. Babic, A. Kučukalić et al.

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.

Mirnesa Muminović Umihanić, R. Babić, N. Kravić, E. Avdibegović, A. Džubur Kulenović, F. Agani, M. Jakovljevič, D. Babic et al.

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.

V. Haxhibeqiri, S. Haxhibeqiri, Valdete Topçiu-Shufta, F. Agani, Aferdita Goci Uka, B. Hoxha, A. Džubur Kulenović, M. Jakovljevič et al.

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.

S. Haxhibeqiri, V. Haxhibeqiri, F. Agani, Aferdita Goci Uka, B. Hoxha, A. Džubur Kulenović, A. Kučukalić, E. Avdibegović et al.

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, β=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.

B. Hoxha, Aferdita Goci Uka, F. Agani, S. Haxhibeqiri, V. Haxhibeqiri, Emina Šabić Džananović, S. Kučukalić, A. Bravo Mehmedbašić et al.

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.

Aferdita Goci Uka, F. Agani, Afrim Blyta, B. Hoxha, S. Haxhibeqiri, V. Haxhibeqiri, Emina Šabić Džananović, S. Kučukalić et al.

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.

N. Jakšić, Emina Šabić Džananović, B. Aukst Margetić, D. Rudan, Ana Čima Franc, N. Božina, Elma Ferić Bojić, S. Kučukalić et al.

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.

S. Kučukalić, Elma Ferić Bojić, R. Babić, E. Avdibegović, D. Babic, F. Agani, M. Jakovljevič, A. Kučukalić et al.

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.

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