RELATIONSHIP OF RELIGIOUSNESS AND RELIGIOUS COPING WITH QUALITY OF LIFE AMONG WAR TRAUMA SURVIVORS

Background: Long-term posttraumatic outcomes such as quality of life are dependent on a series of factors from the very exposure to traumatic events and stress appraisals, personality traits, posttraumatic growth, symptoms of Posttraumatic stress disorder (PTSD) and different coping strategies to religiousness and religious coping styles. Except of exposure to traumatic events and related stress, all other variables may have indirect mediating effects on long-term posttraumatic outcomes. The main aim of this cross-sectional study is to explore relative independent contribution of these variables in the explanation of quality of life among war trauma survivors, with a special emphasis on the variables of religiousness and religious coping. Subjects and methods: The research was conducted on 353 subjects who experienced war related traumatic events during the war in Bosnia and Herzegovina (B&H). The data was collected through several self-report measuring instruments: Manchester Short Assessment of Quality of Life, Stressors Check List (SCL); Religiousness Scale, Social Support Resources Scale; Religious Problem-Solving Scale, Brief RCOPE, Posttraumatic Growth Inventory and Mississippi Scale for PTSD. Results: According to the results of the study, experience of loss and frequent exposure to war trauma and high levels on the primary stress appraisals, self-directing coping style and PTSD-symptoms were associated with lower perceived quality of life among the subjects. High levels of extrinsic religious orientation, effect of religiousness on social behavior, positive religious coping and posttraumatic growth were associated with higher perceived quality of life among subjects. These variables showed significant independent contribution to the prediction of the values on quality of life. Conclusions: Results of the study have a scientific significance in understanding the importance and mediating role of religiousness and religious coping for quality of life perception as one of long-term posttraumatic outcomes. Effects of religiousness on social behavior and positive religious coping showed particularly significant contribution across all prediction models for the quality of life

FEAR AND DEPRESSION AMONG RESIDENTS OF BOSNIA AND HERZEGOVINA DURING COVID-19 OUTBREAK - INTERNET SURVEY

Background: Occurrence of symptoms of fear and depression among general population during the outbreak of COVID-19 seems to present an emerging problem worldwide. The aim of this study was to examine levels of fear and depressive symptoms in association with COVID-19 outbreak and to assess other contributing factors in the population of Bosnia and Herzegovina. Subjects and methods: Link to an anonymous questionnaire, mainly based on The Fear of COVID-19 Scale (Ahorsu et al. 2020) and two item and nine-item Patient Health Questionnaires (PHQs) (Maurer et al. 2018) (background information, fear assessment and information regarding depression) was distributed online to general population of Bosnia and Herzegovina. Results: Out of 1201 respondents, 217 (18.0%) reported experiencing fear and 341 (28.4%) reported having symptoms of depression during COVID-19 outbreak. The mean age of the subjects was 30.57±11.26. Being older (OR=1.044; 95% CI 1.031-1.057; p<0.001) and having moderate to severe depressive symptoms (OR=1.093; 95% CI 1.067 1.120; p<0.001) were independent significant predictors for developing fear; living in rural environment (OR=0.551; 95% Cl 0.325-0.935; p=0.0027) significantly decreased the risk of developing fear; being female (OR=1.750; 95% CI 1.242-2.466; p=0.001), unemployed (OR=1.557; 95% CI 1.040-2.330; p=0.032) or student (OR=1.943; 95% CI 1.450-2.604; p<0.001) were independent significant predictors for developing moderate to severe depressive symptoms in association with COVID-19. Mann Whitney U-test showed that being older was statistically associated with fear (p<0.001) and being younger was statistically associated with depressive symptoms (p<0.001). Conclusions: In conclusion, based on our findings, fear and depressive symptoms in general population of Bosnia and Herzegovina during the outbreak of COVID-19 were present in 18.06% (fear) and 28.39% (depression) of subjects and it was statistically associated with age, gender, occupation, living environment and may present a secondary uprising problem connected to outbreak of COVID-1

CHRONIC ILLNESS AND FAMILY: IMPACT OF SCHIZOPHRENIA AND CROHN’S DISEASE ON THE FAMILY QUALITY OF LIFE

Background: Quality of life assessments are increasingly present in health research. Chronic and progressive illness of a family member unavoidably affects quality of life of a family as a whole.The goals of this study were to gain insight into the family burden of chronic disorders, especially possible differences in family quality of life (FQOL) in families that have members suffering from either schizophrenia or Crohn’s disease, and families in which none of the members have chronic somatic or mental illness, as well as to pilot an instrument for this purpose. Subjects and methods: The sample consisted of 53 families with a member suffering from schizophrenia, 50 families with a member suffering from Crohn\u27s disease, and 45 families with no identifiable chronic illnesses. An informant from each family underwent a structured face to face interview, using a questionnaire specially adapted from Family Quality of Life Survey, an instrument widely used to assess FQOL in families with members with disabilities, and which addresses nine areas of family life. Results: In the domain of health, both groups of families with chronic illnesses believe they have significantly different conditions when compared to members of the Control group. In the Crohn\u27s disease group, families had a great deal more of challenges in accessing healthcare services; and see themselves at a disadvantage when compared to both other groups in the domain of finances. Control group offered lowest rating in the domain of support from others. Overall measures of FQOL show significant variation among the three groups, Crohn’s disease group offering lowest ratings, followed by families of mental health service users. Conclusions: Overall, FQOL seems to be lower in families that have members diagnosed with Crohn’s disease than in families with members suffering from schizophrenia. Illness-specific studies are required, as well as instruments with stronger psychometric properties and studies of determinants of FQOL. Qualitative approach should be emphasised when studying FQOL related to chronic illnesses

ELEVATED SERUM C-REACTIVE PROTEIN LEVEL IS NOT ASSOCIATED WITH SERUM NITRIC OXIDE IN PATIENTS WITH POSTTRAUMATIC STRESS DISORDER

Background: The aim of the present study was to evaluate serum nitric oxide (NO) and C reactive protein (CRP) concentration in veterans with and without PTSD. Furthermore, we aimed to assess whether there is a correlation between serum NO and CRP concentrations in tested groups. Subjects and methods: Cross-sectional study included 90 male individuals, with and without experience of direct war combat, divided into three equal groups (n=30): group 1- included war veterans with PTSD, group 2 - included war veterans without PTSD, and control group - 30 apparently healthy volunteers, without experience of direct war combat. The diagnosis of PTSD was assessed according to the guidelines in the 10th revision of the International Classification of Diseases (ICD-10). High-sensitivity CRP was determined by immunonephelometry. The serum NO level was determined by classic colorimetrical Griess reaction. Results: Serum CRP concentration in veterans with (3.54±1.19 mg/L) and without PTSD (3.24±2.04 mg/L), was significantly higher (p<0.05) compared to control group (1.26±1.06 mg/L). Serum NO concentration in veterans with (7.64±4.43 μmol/L) and without PTSD (7.12±2.60 μmol/L) was significantly lower (p<0.05) compared to control group (11.26±7.01 μmol/L). Statistically significant correlation between serum NO and CRP concentration was determined in veterans without PTSD (r=-0.473; p<0.01). No correlation was observed between serum NO and CRP concentration in veterans with PTSD (r=0.118; p=0.534) and in control group (r=-0.067; p=0.727). Conclusion: The present study has showed significant increase of serum CRP and significant decrease of serum NO concentrations in veterans with and without PTSD. Furthermore, statistically significant negative correlation between serum NO and CRP concentration was determined only in veterans without PTSD. Obtained results indicate that the complex mechanism of the pathogenesis of PTSD requires further research

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\u27s 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 (????=0.002). Conclusion: Nominally significant associations between NPY polymorphisms and PTSD susceptibility were found that did not withstand Bonferroni correction

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. TheFK506-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 (????=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

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 ifetime. 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

Enhancing Discovery of Genetic Variants for Posttraumatic Stress Disorder Through Integration of Quantitative Phenotypes and Trauma Exposure Information

Funding Information: This work was supported by the National Institute of Mental Health / U.S. Army Medical Research and Development Command (Grant No. R01MH106595 [to CMN, IL, MBS, KJRe, and KCK], National Institutes of Health (Grant No. 5U01MH109539 to the Psychiatric Genomics Consortium ), and Brain & Behavior Research Foundation (Young Investigator Grant [to KWC]). Genotyping of samples was provided in part through the Stanley Center for Psychiatric Genetics at the Broad Institute supported by Cohen Veterans Bioscience . Statistical analyses were carried out on the LISA/Genetic Cluster Computer ( https://userinfo.surfsara.nl/systems/lisa ) hosted by SURFsara. This research has been conducted using the UK Biobank resource (Application No. 41209). This work would have not been possible without the financial support provided by Cohen Veterans Bioscience, the Stanley Center for Psychiatric Genetics at the Broad Institute, and One Mind. Funding Information: MBS has in the past 3 years received consulting income from Actelion, Acadia Pharmaceuticals, Aptinyx, Bionomics, BioXcel Therapeutics, Clexio, EmpowerPharm, GW Pharmaceuticals, Janssen, Jazz Pharmaceuticals, and Roche/Genentech and has stock options in Oxeia Biopharmaceuticals and Epivario. In the past 3 years, NPD has held a part-time paid position at Cohen Veterans Bioscience, has been a consultant for Sunovion Pharmaceuticals, and is on the scientific advisory board for Sentio Solutions for unrelated work. In the past 3 years, KJRe has been a consultant for Datastat, Inc., RallyPoint Networks, Inc., Sage Pharmaceuticals, and Takeda. JLM-K has received funding and a speaking fee from COMPASS Pathways. MU has been a consultant for System Analytic. HRK is a member of the Dicerna scientific advisory board and a member of the American Society of Clinical Psychopharmacology Alcohol Clinical Trials Initiative, which during the past 3 years was supported by Alkermes, Amygdala Neurosciences, Arbor Pharmaceuticals, Dicerna, Ethypharm, Indivior, Lundbeck, Mitsubishi, and Otsuka. HRK and JG are named as inventors on Patent Cooperative Treaty patent application number 15/878,640, entitled “Genotype-guided dosing of opioid agonists,” filed January 24, 2018. RP and JG are paid for their editorial work on the journal Complex Psychiatry. OAA is a consultant to HealthLytix. All other authors report no biomedical financial interests or potential conflicts of interest. Funding Information: This work was supported by the National Institute of Mental Health/ U.S. Army Medical Research and Development Command (Grant No. R01MH106595 [to CMN, IL, MBS, KJRe, and KCK], National Institutes of Health (Grant No. 5U01MH109539 to the Psychiatric Genomics Consortium), and Brain & Behavior Research Foundation (Young Investigator Grant [to KWC]). Genotyping of samples was provided in part through the Stanley Center for Psychiatric Genetics at the Broad Institute supported by Cohen Veterans Bioscience. Statistical analyses were carried out on the LISA/Genetic Cluster Computer (https://userinfo.surfsara.nl/systems/lisa) hosted by SURFsara. This research has been conducted using the UK Biobank resource (Application No. 41209). This work would have not been possible without the financial support provided by Cohen Veterans Bioscience, the Stanley Center for Psychiatric Genetics at the Broad Institute, and One Mind. This material has been reviewed by the Walter Reed Army Institute of Research. There is no objection to its presentation and/or publication. The opinions or assertions contained herein are the private views of the authors and are not to be construed as official or as reflecting true views of the U.S. Department of the Army or the Department of Defense. We thank the investigators who comprise the PGC-PTSD working group and especially the more than 206,000 research participants worldwide who shared their life experiences and biological samples with PGC-PTSD investigators. We thank Mark Zervas for his critical input. Full acknowledgments are in Supplement 1. MBS has in the past 3 years received consulting income from Actelion, Acadia Pharmaceuticals, Aptinyx, Bionomics, BioXcel Therapeutics, Clexio, EmpowerPharm, GW Pharmaceuticals, Janssen, Jazz Pharmaceuticals, and Roche/Genentech and has stock options in Oxeia Biopharmaceuticals and Epivario. In the past 3 years, NPD has held a part-time paid position at Cohen Veterans Bioscience, has been a consultant for Sunovion Pharmaceuticals, and is on the scientific advisory board for Sentio Solutions for unrelated work. In the past 3 years, KJRe has been a consultant for Datastat, Inc. RallyPoint Networks, Inc. Sage Pharmaceuticals, and Takeda. JLM-K has received funding and a speaking fee from COMPASS Pathways. MU has been a consultant for System Analytic. HRK is a member of the Dicerna scientific advisory board and a member of the American Society of Clinical Psychopharmacology Alcohol Clinical Trials Initiative, which during the past 3 years was supported by Alkermes, Amygdala Neurosciences, Arbor Pharmaceuticals, Dicerna, Ethypharm, Indivior, Lundbeck, Mitsubishi, and Otsuka. HRK and JG are named as inventors on Patent Cooperative Treaty patent application number 15/878,640, entitled ?Genotype-guided dosing of opioid agonists,? filed January 24, 2018. RP and JG are paid for their editorial work on the journal Complex Psychiatry. OAA is a consultant to HealthLytix. All other authors report no biomedical financial interests or potential conflicts of interest. Publisher Copyright: © 2021 Society of Biological PsychiatryBackground: Posttraumatic stress disorder (PTSD) is heritable and a potential consequence of exposure to traumatic stress. Evidence suggests that a quantitative approach to PTSD phenotype measurement and incorporation of lifetime trauma exposure (LTE) information could enhance the discovery power of PTSD genome-wide association studies (GWASs). Methods: A GWAS on PTSD symptoms was performed in 51 cohorts followed by a fixed-effects meta-analysis (N = 182,199 European ancestry participants). A GWAS of LTE burden was performed in the UK Biobank cohort (N = 132,988). Genetic correlations were evaluated with linkage disequilibrium score regression. Multivariate analysis was performed using Multi-Trait Analysis of GWAS. Functional mapping and annotation of leading loci was performed with FUMA. Replication was evaluated using the Million Veteran Program GWAS of PTSD total symptoms. Results: GWASs of PTSD symptoms and LTE burden identified 5 and 6 independent genome-wide significant loci, respectively. There was a 72% genetic correlation between PTSD and LTE. PTSD and LTE showed largely similar patterns of genetic correlation with other traits, albeit with some distinctions. Adjusting PTSD for LTE reduced PTSD heritability by 31%. Multivariate analysis of PTSD and LTE increased the effective sample size of the PTSD GWAS by 20% and identified 4 additional loci. Four of these 9 PTSD loci were independently replicated in the Million Veteran Program. Conclusions: Through using a quantitative trait measure of PTSD, we identified novel risk loci not previously identified using prior case-control analyses. PTSD and LTE have a high genetic overlap that can be leveraged to increase discovery power through multivariate methods.publishersversionpublishe