Publications by authors named "Branka Aukst-Margetic"

80 Publications

Association of polygenic risk scores, traumatic life events and coping strategies with war-related PTSD diagnosis and symptom severity in the South Eastern Europe (SEE)-PTSD cohort.

J Neural Transm (Vienna) 2021 Nov 27. Epub 2021 Nov 27.

Department of Psychiatry, University Clinical Center, Sarajevo, Bosnia and Herzegovina.

Objectives: Posttraumatic stress disorder (PTSD) is triggered by extremely stressful environmental events and characterized by high emotional distress, re-experiencing of trauma, avoidance and hypervigilance. The present study uses polygenic risk scores (PRS) derived from the UK Biobank (UKBB) mega-cohort analysis as part of the PGC PTSD GWAS effort to determine the heritable basis of PTSD in the South Eastern Europe (SEE)-PTSD cohort. We further analyzed the relation between PRS and additional disease-related variables, such as number and intensity of life events, coping, sex and age at war on PTSD and CAPS as outcome variables.

Methods: Association of PRS, number and intensity of life events, coping, sex and age on PTSD were calculated using logistic regression in a total of 321 subjects with current and remitted PTSD and 337 controls previously subjected to traumatic events but not having PTSD. In addition, PRS and other disease-related variables were tested for association with PTSD symptom severity, measured by the Clinician Administrated PTSD Scale (CAPS) by liner regression. To assess the relationship between the main outcomes PTSD diagnosis and symptom severity, each of the examined variables was adjusted for all other PTSD related variables.

Results: The categorical analysis showed significant polygenic risk in patients with remitted PTSD and the total sample, whereas no effects were found on symptom severity. Intensity of life events as well as the individual coping style were significantly associated with PTSD diagnosis in both current and remitted cases. The dimensional analyses showed as association of war-related frequency of trauma with symptom severity, whereas the intensity of trauma yielded significant results independently of trauma timing in current PTSD.

Conclusions: The present PRS application in the SEE-PTSD cohort confirms modest but significant polygenic risk for PTSD diagnosis. Environmental factors, mainly the intensity of traumatic life events and negative coping strategies, yielded associations with PTSD both categorically and dimensionally with more significant p-values. This suggests that, at least in the present cohort of war-related trauma, the association of environmental factors and current individual coping strategies with PTSD psychopathology was stronger than the polygenic risk.
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http://dx.doi.org/10.1007/s00702-021-02446-5DOI Listing
November 2021

COGNITIVE AND PSYCHOTIC SYMPTOMS IN A PATIENT WITH INFRATENTORIAL ARACHNOID CYST: CASE REPORT.

Acta Clin Croat 2021 Jun;60(2):304-308

1Department of Psychiatry, Dr. Ivan Barbot Neuropsychiatric Hospital, Popovača, Croatia; 2Department of Psychiatry, Sestre milosrdnice University Hospital Centre, Zagreb, Croatia.

We present a case of a patient with treatment resistant hallucinatory experiences with incidental finding of an arachnoid cyst localized in the posterior infratentorial cranial fossa dorsally to the cerebellum. Psychological testing revealed significant deficit of cognitive functions to the level of mild intellectual disability in a person that had previously finished high school with good grades. A combination of clozapine and lamotrigine led to significant improvement in mood and reduction of hallucinations, but without improvement in cognitive functions. We also performed a literature review of previously published case reports or case series of co-occurring posterior fossa arachnoid cyst and schizophrenia or psychosis or psychiatric symptoms using PubMed search and discuss some controversies considering their treatment outcome.
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http://dx.doi.org/10.20471/acc.2021.60.02.18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8564833PMC
June 2021

Schyzotipy: from Personality Organization to Transition to Schizophrenia.

Psychiatr Danub 2021 Spring-Summer;33(Suppl 4):529-534

Department of Psychiatry, University Hospital Center Sestre milosrdnice, Vinogradska 29, 10000 Zagreb, Croatia,

The traditional medical model of schizophrenia assumes a categorical view of the syndrome. On the contrary, the dimensional approach to schizophrenia infers that schizophrenia is not a discrete illness entity, but that psychotic symptoms differ in quantitative ways from normal experiences and behaviours. Schizotypy comprise a set of inherited traits reflected in personality organization, which presents as qualitatively similar to schizophrenia. Schizotipy is in line with continuum hypothesis of schizophrenia where different combinations of genes and environmental risk factors result in a range of different phenotypic expressions lying on a continuum from normal through to clinical psychosis. We discuss evidences for the continuity of psychotic symptoms to normal experiences and theoretical and future research implications of such a continuum.
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November 2021

EIGHTY YEARS OF ELECTROCONVULSIVE THERAPY IN CROATIA AND IN SESTRE MILOSRDNICE UNIVERSITY HOSPITAL CENTRE.

Acta Clin Croat 2020 Sep;59(3):489-495

1Department of Psychiatry, Sestre milosrdnice University Hospital Centre, Zagreb, Croatia; 2School of Dental Medicine, University of Zagreb, Zagreb, Croatia; 3Catholic University of Croatia, Zagreb, Croatia; 4Department of Anesthesiology, Intensive Care and Pain Therapy, Sestre milosrdnice University Hospital Centre, Zagreb, Croatia.

In 1937, Ugo Cerletti and Lucio Bini performed electroconvulsive treatment (ECT) in Rome for the first time. That was the time when different types of 'shock therapy' were performed; beside ECT, insulin therapies, cardiazol shock therapy, etc. were also performed. In 1938, Cerletti and Bini reported the results of ECT. Since then, this method has spread rapidly to a large number of countries. As early as 1940, just two years after the results of the ECT had been published, it was also introduced in Croatia, at Sestre milosrdnice Hospital, for the first time in our hospital and in the then state of Yugoslavia. Since 1960, again the first in Croatia and the state, we performed ECT in general anesthesia and continued it down to the present, with a single time brake.
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http://dx.doi.org/10.20471/acc.2020.59.03.13DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8212646PMC
September 2020

Personality and Stigma in Lung Cancer Patients.

Psychiatr Danub 2020 Nov;32(Suppl 4):528-532

Department of Psychiatry, University Hospital Sestre Milosrdnice, Vinogradska cesta 29, 10000 Zagreb, Croatia,

Background: Stigma in lung cancer has been associated with diagnostic and treatment delay and with poor outcomes. Personality has impact on the perception of someone's life situation and interacts with psychosocial variables and coping strategies. The vulnerability to stigma is still under-researched. The aim of this study was to investigate this vulnerability by examining the associations between stigma and personality dimensions (i.e., temperament and character traits).

Subjects And Methods: Seventy six (76) inpatients of the two teaching hospitals with the diagnosis of non-small-cell lung cancer were consecutively included in the study. Patients were assessed with self-reporting scales: Cataldo Lung Cancer Stigma Scale (CLCSS) and Temperament and Character Inventory (TCI). Sociodemographic and clinical data were also collected.

Results: Personality dimensions Self-directedness and Persistence showed to be significant predictors of stigma in the linear regression (R=0.519; F=3.104; P=0.007). Stigma and personality dimensions were not associated with age, gender, tumor stage and smoking status.

Conclusion: Stigma is associated with particular character (i.e., Self-directedness) and temperament (i.e., Persistence) dimensions. Given the negative clinical outcomes of stigma in lung cancer patients, personality should be taken into account during screening and treatment planning phases.
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November 2020

Temperament, Character, and Subjective Well-Being in Croatian War Veterans Suffering From Posttraumatic Stress Disorder.

J Nerv Ment Dis 2020 04;208(4):340-343

Department of Psychological Medicine, University Hospital Center Zagreb, Zagreb, Croatia.

Subjective well-being is decreased in war-affected populations. However, no previous research has investigated the role of temperament and character dimensions in life satisfaction among war veterans with posttraumatic stress disorder (PTSD). This study enrolled 148 Croatian male war veterans being treated for combat-related PTSD. The participants completed the Beck Depression Inventory-Second Edition, Satisfaction with Life Scale, and Temperament and Character Inventory-Revised. Two multivariate regression analyses with life satisfaction as a dependent variable and temperament and character dimensions, respectively, as predictor variables, were performed. Temperament dimensions harm avoidance and novelty seeking as well as character dimensions self-directedness and cooperativeness were unique predictors of life satisfaction, while controlling for the influence of depressive symptoms, education level, and employment status. Given the influence of personality dimensions on life satisfaction, the routine assessment of these dimensions might help to establish the individually tailored treatment among war veterans with PTSD.
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http://dx.doi.org/10.1097/NMD.0000000000001127DOI Listing
April 2020

A Candidate Gene Association Study of FKBP5 and CRHR1 Polymorphisms in Relation to War-Related Posttraumatic Stress Disorder.

Psychiatr Danub 2019 Jun;31(2):269-275

Department of Psychiatry, University Hospital Centre Zagreb, Kispaticeva 12, 10000 Zagreb, Croatia,

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.
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http://dx.doi.org/10.24869/psyd.2019.269DOI Listing
June 2019

The Role of TaqI DRD2 (rs1800497) and DRD4 VNTR Polymorphisms in Posttraumatic Stress Disorder (PTSD).

Psychiatr Danub 2019 Jun;31(2):263-268

Department of Psychiatry, University Clinical Centre of Kosovo, Prishtina, Kosovo,

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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http://dx.doi.org/10.24869/psyd.2019.263DOI Listing
June 2019

Role of the Allelic Variation in the 5-Hydroxytryptamine Receptor 1A (HTR1A) and the Tryptophan Hydroxylase 2 (TPH2) Genes in the Development of PTSD.

Psychiatr Danub 2019 Jun;31(2):256-262

Department of Psychiatry, University Clinical Centre of Kosovo, Str, Hile Mosi, nr 11, 10000 Prishtina, Kosovo,

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.
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http://dx.doi.org/10.24869/psyd.2019.256DOI Listing
June 2019

Association of Neuropeptide S Receptor 1 and Glutamate Decarboxylase 1 Gene Polymorphisms with Posttraumatic Stress Disorder.

Psychiatr Danub 2019 Jun;31(2):249-255

Institute of Kosovo Forensic Psychiatry, University Clinical Centre of Kosovo, Prishtina, Kosovo.

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.
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http://dx.doi.org/10.24869/psyd.2019.249DOI Listing
June 2019

The Association of Catechol-O-Methyl-Transferase and Interleukin 6 Gene Polymorphisms with Posttraumatic Stress Disorder.

Psychiatr Danub 2019 Jun;31(2):241-248

Department of Clinical Biochemistry, University Clinical Centre of Kosovo, Prishtina, Kosovo.

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.
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http://dx.doi.org/10.24869/psyd.2019.241DOI Listing
June 2019

Associations between Polymorphisms in the Solute Carrier Family 6 Member 3 and the Myelin Basic Protein Gene and Posttraumatic Stress Disorder.

Psychiatr Danub 2019 Jun;31(2):235-240

Community Health Center Zivinice, Alije Izetbegovica 17, 75270 Zivinice, Bosnia & Herzegovina,

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.
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http://dx.doi.org/10.24869/psyd.2019.235DOI Listing
June 2019

Associations of Gene Variations in Neuropeptide Y and Brain Derived Neurotrophic Factor Genes with Posttraumatic Stress Disorder.

Psychiatr Danub 2019 Jun;31(2):227-234

International Burch University, Department of Genetics and Bioengineering, Francuske revolucije bb, 71000 Sarajevo, Bosnia and Herzegovina,

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's 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 (α=0.002).

Conclusion: Nominally significant associations between NPY polymorphisms and PTSD susceptibility were found that did not withstand Bonferroni correction.
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http://dx.doi.org/10.24869/psyd.2019.227DOI Listing
June 2019

Genetic Susceptibility to Posttraumatic Stress Disorder: Analyses of the Oxytocin Receptor, Retinoic Acid Receptor-Related Orphan Receptor A and Cannabinoid Receptor 1 Genes.

Psychiatr Danub 2019 Jun;31(2):219-226

Department of Psychiatry, Clinical Center University Sarajevo, Bolnička 25, 71000 Sarajevo, Bosnia and Herzegovina,

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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http://dx.doi.org/10.24869/psyd.2019.219DOI Listing
June 2019

Association Analysis of Maoa and Slc6a4 Gene Variation in South East European War Related Posttraumatic Stress Disorder.

Psychiatr Danub 2019 Jun;31(2):211-218

Department of Psychiatry, University Clinical Centre Tuzla, Rate Dugonjića bb, 75000 Tuzla, Bosnia and Herzegovina,

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.
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http://dx.doi.org/10.24869/psyd.2019.211DOI Listing
June 2019

Temperament and character in homicidal patients with schizophrenia.

Nord J Psychiatry 2019 Aug 19;73(6):317-322. Epub 2019 Jun 19.

c Department of Psychology, Faculty of Humanities and Social Sciences , Zagreb , Croatia.

Understanding the etiology of violence in patients with schizophrenia is an issue of great clinical and public importance. Although personality traits are an important aspect in determining complex behaviors of schizophrenia patients, there is a lack of research on the relationship between personality traits and violence, especially homicidal behavior, in this population. We aimed to compare temperament and character dimensions between homicidal and other mostly violent forensic patients with schizophrenia, and to determine which temperament and character dimensions are associated with homicidal behavior in these patients. : We recruited 71 male forensic schizophrenia patients without concomitant substance dependence and antisocial personality disorder. The patients were divided into two groups according to trial documentation as: (1) Homicide and attempted homicide group (N 30; 42%), and (2) Other offenses group (N 41; 58%). Patients were assessed by means of the Temperament and Character Inventory and the Positive and Negative Syndrome Scale. Differences between groups were tested with -test. : The two groups of patients were similar in their PANSS scores, but the homicidal men were significantly more likely to show higher harm avoidance (HA) scores than the less violent comparison men ( = 2,876, df-69,  = 0.005). : Our results indicate that forensic schizophrenic patients with higher HA scores would show a greater risk of homicidal violence. Improved understanding of personality traits associated with such behavior is needed in order to prevent homicidal behavior. Importance of these results suggests that further study is needed.
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http://dx.doi.org/10.1080/08039488.2019.1630482DOI Listing
August 2019

Neuregulin-1 is increased in schizophrenia patients with chronic cannabis abuse: Preliminary results.

Schizophr Res 2019 06 22;208:473-474. Epub 2019 Feb 22.

Department of Psychiatry, University Hospital Center "Sestre milosrdnice", Zagreb, Croatia; Catholic University of Croatia, Zagreb, Croatia.

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http://dx.doi.org/10.1016/j.schres.2019.02.007DOI Listing
June 2019

Monoamine Oxidase A Gene Methylation and Its Role in Posttraumatic Stress Disorder: First Evidence from the South Eastern Europe (SEE)-PTSD Study.

Int J Neuropsychopharmacol 2018 05;21(5):423-432

Department of Psychiatry, Psychosomatics and Psychotherapy, University of Würzburg, Würzburg, Germany.

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.
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http://dx.doi.org/10.1093/ijnp/pyx111DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5932467PMC
May 2018

Socio-Cultural Effects on Mental Health and Common Chronic Diseases in Primary Care Patients in East and West Mostar, Bosnia and Herzegovina: Preliminary Results.

Acta Clin Croat 2016 06;55(2):187-94

School of Medicine, University of Mostar, Mostar, Bosnia and Herzegovina

Since war activities, the previously mixed population of Mostar, Bosnia and Herzegovina, live in segregated parts of the town based on ethnicity. The aim of this study was to examine differences in health risks and health status between populations of the two parts of the town. Health status of 300 randomly selected primary care patients was evaluated by practicing family physicians in two main primary care centers in West and East Mostar. Each group consisted of 150 patients. Data were collected between December 2013 and May 2014. Patients were evaluated for smoking habit, alcohol consumption, body mass index, blood pressure and laboratory measurement of fasting glycemia. Family physicians provided diagnosis of chronic noninfectious diseases (hypertension, diabetes mellitus, cardiovascular disease, malignant disease, depression, and alcoholism). The two groups differed according to age, income, employment status, and rate of alcoholism and hypertension. Alcoholism (OR= 4.105; 95% CI 2.012-8.374) and hypertension (OR=1.972; 95% CI 1.253-3.976) were associated with inhabitants of West Mostar, adjusted for age, employment and income status on logistic regression. In conclusion, ethnic differences between inhabitants of the two parts of the town might influence health outcomes. These are preliminary data and additional studies with larger samples and more specific questions considering nutrition and cultural issues are needed to detect the potential differences between the groups.
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http://dx.doi.org/10.20471/acc.2016.55.02.02DOI Listing
June 2016

Socio-Cultural Effects on Mental Health and Common Chronic Diseases in Primary Care Patients in East and West Mostar, Bosnia and Herzegovina: Preliminary Results.

Acta Clin Croat 2016 06;55(2):187-94

School of Medicine, University of Mostar, Mostar, Bosnia and Herzegovina

Since war activities, the previously mixed population of Mostar, Bosnia and Herzegovina, live in segregated parts of the town based on ethnicity. The aim of this study was to examine differences in health risks and health status between populations of the two parts of the town. Health status of 300 randomly selected primary care patients was evaluated by practicing family physicians in two main primary care centers in West and East Mostar. Each group consisted of 150 patients. Data were collected between December 2013 and May 2014. Patients were evaluated for smoking habit, alcohol consumption, body mass index, blood pressure and laboratory measurement of fasting glycemia. Family physicians provided diagnosis of chronic noninfectious diseases (hypertension, diabetes mellitus, cardiovascular disease, malignant disease, depression, and alcoholism). The two groups differed according to age, income, employment status, and rate of alcoholism and hypertension. Alcoholism (OR= 4.105; 95% CI 2.012-8.374) and hypertension (OR=1.972; 95% CI 1.253-3.976) were associated with inhabitants of West Mostar, adjusted for age, employment and income status on logistic regression. In conclusion, ethnic differences between inhabitants of the two parts of the town might influence health outcomes. These are preliminary data and additional studies with larger samples and more specific questions considering nutrition and cultural issues are needed to detect the potential differences between the groups.
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June 2016

Socio-Cultural Effects on Mental Health and Common Chronic Diseases in Primary Care Patients in East and West Mostar, Bosnia and Herzegovina: Preliminary Results.

Acta Clin Croat 2016 06;55(2):187-94

School of Medicine, University of Mostar, Mostar, Bosnia and Herzegovina

Since war activities, the previously mixed population of Mostar, Bosnia and Herzegovina, live in segregated parts of the town based on ethnicity. The aim of this study was to examine differences in health risks and health status between populations of the two parts of the town. Health status of 300 randomly selected primary care patients was evaluated by practicing family physicians in two main primary care centers in West and East Mostar. Each group consisted of 150 patients. Data were collected between December 2013 and May 2014. Patients were evaluated for smoking habit, alcohol consumption, body mass index, blood pressure and laboratory measurement of fasting glycemia. Family physicians provided diagnosis of chronic noninfectious diseases (hypertension, diabetes mellitus, cardiovascular disease, malignant disease, depression, and alcoholism). The two groups differed according to age, income, employment status, and rate of alcoholism and hypertension. Alcoholism (OR= 4.105; 95% CI 2.012-8.374) and hypertension (OR=1.972; 95% CI 1.253-3.976) were associated with inhabitants of West Mostar, adjusted for age, employment and income status on logistic regression. In conclusion, ethnic differences between inhabitants of the two parts of the town might influence health outcomes. These are preliminary data and additional studies with larger samples and more specific questions considering nutrition and cultural issues are needed to detect the potential differences between the groups.
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June 2016

Do spirituality and religiousness differ with regard to personality and recovery from depression? A follow-up study.

Compr Psychiatry 2016 10 14;70:17-24. Epub 2016 Jun 14.

School of public health Andrija Stampar, Rockfellerova4, 10000, Zagreb, Croatia.

Background: The studies show that both spirituality and religiousness are protective for mental health. Personality is related with course and outcome of depression, as well as spirituality and religiousness, and their relations toward to recovery from depression are underresearched. This study followed influence of spirituality and religiousness on course and outcome of depression in patients with depressive episode, controlled for personality dimensions.

Methods: The patients were assessed with self-report measures of depression (Beck Depression Inventory), spirituality (WHO-Quality of Life-Spiritual, Religious, Personal Beliefs), religiousness (Duke University Religion Index) and personality (Temperament and Character Inventory). Ninety nine patients finished a year long follow up.

Results: Higher spirituality influenced recovery of depression in patients with depressive episode, but religiousness did not show to be significant predictor of recovery for depression. Dimension harm avoidance was significant predictor of improvement of depression in all points of measurement.

Limitations: Some limitations of this research are small sample size, usage of the self-report measures of depression in follow-up period, and the predominantly Catholic affiliation of the participants that can impact the generalizability of our data to other denominations.

Conclusion: Spirituality and dimension harm avoidance are significant predictors of recovery from depression during a year long follow up.
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http://dx.doi.org/10.1016/j.comppsych.2016.06.003DOI Listing
October 2016

Religiosty and Mental Health in Nursing Students.

Psychiatr Danub 2016 Jun;28(2):188-92

Faculty of Health Studies, University of Mostar, Mostar, Bosnia and Herzegovina.

Background: Young people and nursing students are prone to stress and psychological consequences of it. The aim of the current study was to assess the associations between psychopathology and religiosity in the group of nursing university students.

Subjects And Methods: The study included 100 nursing students of the Faculty of Health Studies in Mostar. The participants were assessed with the SLC-90-R and Dimensions of Religiosity Questionnaire. Sociodemographic data were also collected.

Results: All SCL-90-R subscales negatively correlated with religiosity showing that the strength of religiosity was associated with better mental health of nursing students. Twenty two percent of potential cases of mental disorder were detected based on the GSI cut-off score. Religiosity was a significant predictor of mental disorder in logistic regression based on the GSI. The year of the study and quality of family relations were associated with students' religiosity. Gender, socioeconomic status and parents' education were associated with higher psychopathology scores.

Conclusion: Religiosity showed to be important factor of resilience for nursing students. Further studies are needed.
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June 2016

Molecular Mechanisms of Posttraumatic Stress Disorder (PTSD) as a Basis for Individualized and Personalized Therapy: Rationale, Design and Methods of the South Eastern Europe (SEE)-PTSD study.

Psychiatr Danub 2016 Jun;28(2):154-63

Department of Psychiatry, University Clinical Center Sarajevo, Bolnicka 25, 71000 Sarajevo, Bosnia and Herzegovina,

Posttraumatic Stress Disorder (PTSD) is a major health problem in South Eastern Europe (SEE). Available treatment options are not efficient enough and the course is often chronic. Little is known about molecular mediators and moderators of pathogenesis and therapy. Genetic and epigenetic variation may be one central molecular mechanism. We therefore established a consortium combining clinical expertise on PTSD from SEE countries Bosnia-Herzegovina (Sarajevo, Tuzla and Mostar), Kosovo (Prishtina) and Croatia (Zagreb) with genetic and epigenetic competence from Germany (Würzburg) in 2011 within the framework of the DAAD (Deutscher Akademischer Austauschdienst)-funded Stability Pact for South Eastern Europe. After obtaining ethical votes and performing rater trainings as well as training in DNA extraction from EDTA blood between 2011 and 2013, we recruited 747 individuals who had experienced war-related trauma in the SEE conflicts between 1991 and 1999. 236 participants had current PTSD, 161 lifetime PTSD and 350 did not have and never had PTSD. Demographic and clinical data are currently merged together with genetic and epigenetic data in a single database to allow for a comprehensive analysis of the role of genetic and epigenetic variation in the pathogenesis and therapy of PTSD. Analyses will be done to a great degree by PhD students from participating SEE centers who in addition to participation in the project had an opportunity to take part in spring and summer schools of the DFG (Deutsche Forschungsgemeinschaft) funded Research Training Group (RTG) 1253 and thus meet PhD students from Germany and other countries We are confident that our project will not only contribute to a better understanding of genetic and epigenetic mechanisms of PTSD as a basis for future individualized and personalized therapies, but also to the academic development of South Eastern Europe.
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June 2016

Personality traits and treatment compliance in patients with type 2 diabetes mellitus.

Psychiatr Danub 2015 Dec;27 Suppl 2:586-9

Department of Psychiatry, University Hospital Center Mostar, Mostar, Bosnia and Herzegovina,

Background: Personality traits, especially types A/B and D, have been linked to negative outcomes in various somatic illnesses. In this study, we aimed to assess the prevalence of personality types and their association with certain aspects of treatment compliance in patients with type 2 diabetes mellitus (T2DM).

Subjects And Methods: Participants in this study were 91 in- and outpatients suffering from T2DM and 73 healthy control subjects. All the participants filled out standardized self-report measures of personality types A/B (Bortner Rating Scale) and D (Type D Scale; DS-14). In addition, two aspects of treatment compliance were assessed: blood glucose assessment and visits to the primary care physician.

Results: We found a higher incidence of personality type B (χ(2)=4.086, p=0.049) and personality type D (χ(2)=4.215, p=0.048) in the group of T2DM patients compared to healthy controls. Patients with type D personality were less compliant in terms of the visits to the primary care physician (χ(2)=4.229, p=0.040), although they were more prevalent among those who were compliant regarding the frequency of blood glucose assessment (χ(2)=4.022, p=0.045).

Conclusion: The current study shows that type B and type D personality are frequent among T2DM patients. Moreover, type D personality could lead to certain aspects of suboptimal health behaviors and, therefore, interfere with disease management in diabetic populations.
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December 2015

Personality traits and treatment compliance in patients with type 2 diabetes mellitus.

Psychiatr Danub 2015 Dec;27 Suppl 2:586-9

Department of Psychiatry, University Hospital Center Mostar, Mostar, Bosnia and Herzegovina,

Background: Personality traits, especially types A/B and D, have been linked to negative outcomes in various somatic illnesses. In this study, we aimed to assess the prevalence of personality types and their association with certain aspects of treatment compliance in patients with type 2 diabetes mellitus (T2DM).

Subjects And Methods: Participants in this study were 91 in- and outpatients suffering from T2DM and 73 healthy control subjects. All the participants filled out standardized self-report measures of personality types A/B (Bortner Rating Scale) and D (Type D Scale; DS-14). In addition, two aspects of treatment compliance were assessed: blood glucose assessment and visits to the primary care physician.

Results: We found a higher incidence of personality type B (χ(2)=4.086, p=0.049) and personality type D (χ(2)=4.215, p=0.048) in the group of T2DM patients compared to healthy controls. Patients with type D personality were less compliant in terms of the visits to the primary care physician (χ(2)=4.229, p=0.040), although they were more prevalent among those who were compliant regarding the frequency of blood glucose assessment (χ(2)=4.022, p=0.045).

Conclusion: The current study shows that type B and type D personality are frequent among T2DM patients. Moreover, type D personality could lead to certain aspects of suboptimal health behaviors and, therefore, interfere with disease management in diabetic populations.
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December 2015

Neglected issues in follow-up of psychiatric patients with hyponatremia.

Psychiatry Res 2015 Jan 13;225(1-2):221-222. Epub 2014 Nov 13.

Department of Psychiatry, University Hospital Center Zagreb, Kišpatićeva 12, 10000 Zagreb, Croatia.

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http://dx.doi.org/10.1016/j.psychres.2014.11.014DOI Listing
January 2015

Neglected issues in follow-up of psychiatric patients with hyponatremia.

Psychiatry Res 2015 Jan 13;225(1-2):221-222. Epub 2014 Nov 13.

Department of Psychiatry, University Hospital Center Zagreb, Kišpatićeva 12, 10000 Zagreb, Croatia.

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January 2015
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