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Modern psychiatric treatment is largely dictated by national and international guidelines rested on evidence-based data, including psychopharmacotherapy and psychotherapy. An alternative to the rigid application of official guidelines and criterion for the standards of treatment in psychiatric practice is the concept of creative psychopharmacotherapy. It is a concept based on the integration of different approaches to a person as whole, mental disorders and their treatment into person-centered clinical practice. In this sense, group psychotherapy and creative psychopharmacotherapy today are part of the overall integrative efforts in psychiatry. Neuroscientific discoveries suggest that they share similar neural pathways that lead to changes in brain function and symptoms relief. Various integrative elements make group psychotherapy and psychopharmacotherapy in combination more effective and efficient. The integration of the concept of creative psychopharmacotherapy and group psychotherapy into everyday clinical practice can improve treatment options as well as clinical practice by creating opportunities for research and development of new modalities of overall treatment.

J. Mundy, Christopher Hübel, J. Gelernter, D. Levey, R. Murray, M. Skelton, Murray B. Stein, Adam X. Caroline M. Dewlen G. Victoria B. Joseph R. San Maihofer Nievergelt Baker Risborough Calabrese Gal et al.

Abstract Background Posttraumatic stress disorder (PTSD) and major depressive disorder (MDD) are commonly reported co-occurring mental health consequences of psychological trauma exposure. The disorders have high genetic overlap. Trauma is a complex phenotype but research suggests that trauma sensitivity has a heritable basis. We investigated whether sensitivity to trauma in those with MDD reflects a similar genetic component in those with PTSD. Methods Genetic correlations between PTSD and MDD in individuals reporting trauma and MDD in individuals not reporting trauma were estimated, as well as with recurrent MDD and single-episode MDD, using genome-wide association study (GWAS) summary statistics. Genetic correlations were replicated using PTSD data from the Psychiatric Genomics Consortium and the Million Veteran Program. Polygenic risk scores were generated in UK Biobank participants who met the criteria for lifetime MDD (N = 29 471). We investigated whether genetic loading for PTSD was associated with reporting trauma in these individuals. Results Genetic loading for PTSD was significantly associated with reporting trauma in individuals with MDD [OR 1.04 (95% CI 1.01–1.07), Empirical-p = 0.02]. PTSD was significantly more genetically correlated with recurrent MDD than with MDD in individuals not reporting trauma (rg differences = ~0.2, p < 0.008). Participants who had experienced recurrent MDD reported significantly higher rates of trauma than participants who had experienced single-episode MDD (χ2 > 166, p < 0.001) Conclusions Our findings point towards the existence of genetic variants associated with trauma sensitivity that might be shared between PTSD and MDD, although replication with better powered GWAS is needed. Our findings corroborate previous research highlighting trauma exposure as a key risk factor for recurrent MDD.

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.

The risk of posttraumatic stress disorder (PTSD) following trauma is heritable, but robust common variants have yet to be identified. In a multi-ethnic cohort including over 30,000 PTSD cases and 170,000 controls we conduct a genome-wide association study of PTSD. We demonstrate SNP-based heritability estimates of 5–20%, varying by sex. Three genome-wide significant loci are identified, 2 in European and 1 in African-ancestry analyses. Analyses stratified by sex implicate 3 additional loci in men. Along with other novel genes and non-coding RNAs, a Parkinson’s disease gene involved in dopamine regulation, PARK2, is associated with PTSD. Finally, we demonstrate that polygenic risk for PTSD is significantly predictive of re-experiencing symptoms in the Million Veteran Program dataset, although specific loci did not replicate. These results demonstrate the role of genetic variation in the biology of risk for PTSD and highlight the necessity of conducting sex-stratified analyses and expanding GWAS beyond European ancestry populations. Post-traumatic stress disorder (PTSD) is a common mental health problem. Here, the authors report a GWAS from the Psychiatric Genomics Consortium in which they identify two risk loci in European ancestry and one locus in African ancestry individuals and find that PTSD is genetically correlated with several other psychiatric traits.

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.

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

BackgroundConflict-related sexual violence (CRSV) was committed on a large scale against women across Bosnia and Herzegovina (BiH) during the 1990’s war, and research has shown both negative and positive psychosocial outcomes following such acts of interpersonal violence. We aim to determine the capacity for posttraumatic growth (PTG) among a population of women who experienced CRSV, and to what extent it is impacted by factors such as coping and optimism.MethodsThis study sought to examine the relationship between PTG (posttraumatic growth inventory), symptoms of posttraumatic stress disorder (PTSD; Harvard Trauma Questionnaire) and dispositional factors such as coping (COPE) and optimism (Life-Orientation Test-Revised) in a sample of n = 104 women. We first conducted bivariate correlations and then hierarchical linear regression analyses, and hypothesized that approach coping strategies and optimism will act to enhance PTG.ResultsFindings showed that the average total score for PTG in this study was 58.94 (SD = 23.01), and current PTSD symptomatology above a threshold of > 2.5 was detected in 92.3% (n = 96) participants (mean score 3.18, SD = .45). Bivariate correlations showed that higher levels of PTG were associated with greater optimism, greater approach coping strategies positive reinterpretation and planning, and lower avoidance strategies behavioural disengagement and substance use. When entered into a regression model, only positive reinterpretation and behavioural disengagement remained, the R-square of the total set of predictors was 0.16, thus explaining 16% of PTG total score.ConclusionTwo types of coping (namely capacity of both greater positive reinterpretation and lower behavioural disengagement) most strongly predicted growth after trauma in this sample of CRSV survivors from BiH. These dimensions of coping confirm the role of coping strategies in the development of PTG. Further research would be useful in corroborating these findings in other post-conflict settings, and delving further into the possibility of a dual mechanism of growth and distress after CRSV.

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.

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.

Blerina 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.

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