STIGMA OF PSYCHIATRIC DISEASES AND PSYCHIATRY

The aim of this review is evaluate stigma seen among people suffering from psychiatric disorders. We will show the negative effects of stigma on psychiatric services and evaluate the importance of continiuous anti-stigma programs. It is encouraging that new anit-stigma programmes are developed. The aim of this program is the restoration of dignity to patients and institutions. Media play an important role in shaping the view of an average person on psychiatric patients and most programms use media as a mediator to promote a positive attitude to psychiatric disorders. Apart from ignorance, fear and hostility they have to deal with self-stigma, as well. Through anti-stigma programs, psychoeducation of patients and families about the disorder and treatment options we can give them an acitve role in the treatment, restore dignity, self-confidence, quality of life and reintegrate them into the society

ASSOCIATION OF NEUROPEPTIDE S RECEPTOR 1 AND GLUTAMATE DECARBOXYLASE 1 GENE POLYMORPHISMS WITH POSTTRAUMATIC STRESS DISORDER

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, ????=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

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

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

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

THE ASSOCIATION OF CATECHOL-O-METHYL-TRANSFERASE AND INTERLEUKIN 6 GENE POLYMORPHISMS WITH POSTTRAUMATIC STRESS DISORDER

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

Paroxetine in the Treatment of Post Traumatic Stress Disorder: Our Experiences

Posttraumatic stress disorder can develop after individual’s exposure or witnessing of life threatening events. It is characterized by three clusters of symptoms. The course of PTSD is often chronic and impedes individual’s functioning. Studies of PTSD treatment with paroxetine provide evidence for its efficacy in reducing symptoms and its favorable profile of side-effects. The objective of this work was to determine the efficacy of paroxetine in the treatment of PTSD. The sample consisted of 30 subjects with chronic PTSD. All subjects received treatment with paroxetine in therapeutic dose range for six months. Subjects were assessed prior to therapy and following six months of treatment with paroxetine with the use of following instruments: SCL 90-R, Mississippi Questionnaire, and CGI. The results indicate statistically significant reduction on all subscales of SCL 90-R following six months of treatment, P<0,05. The difference between two assessments with Mississippi Questionnaire was statistically significant, P< 0,05. PTSD rate in our sample was reduced from 100% before treatment to 64% after treatment. Paroxetine was administered in daily dose of 20 mg in 88% of the subjects, and 40 mg in the remaining 12%. Unwanted effects were registered in 16,7% of the subjects and they were mild. Objective improvement was registered in 84% of the sample, and subjective improvement was registered in 80%. Reduction of relapse symptoms was registered in 24% of the subjects. Paroxetine proved to be efficient and safe in treatment of symptoms of PTSD in this study

IMPACT OF CHRONIC POSTTRAUMATIC STRESS DISORDER ON THE QUALITY OF LIFE OF WAR SURVIVORS

Background: Research data from studies of functional neuroanatomy and neurochemistry indicate various dysfunctions in certain areas of the brain in individuals who suffer from chronic Posttraumatic Stress Disorder. These abnormalities are involved in the evolution of symptoms of PTSD, deterioration of cognitive functions and decreased quality of life of the survivors. The intensity of these symptoms is in direct correlation with the degree of dysfunction in the central nervous system. The aim of our study, was to evaluate the subjective perception of the Quality of life in subjects suffering from chronic PTSD and to compare prior to treatment results to results three and six months after receiving therapy, as well as to analyze whether perception of the Quality of life change related to treatment. The study was conducted at the Psychiatric Clinic of the Sarajevo University Clinical Center. Subjects and methods: The sample consisted of 100 male persons, with war trauma experiences, whose age range was between 35 and 60 years, who were seeking treatment at the Psychiatric Clinic, University of Sarajevo Clinical Center and met the criteria for the diagnosis of chronic PTSD (Posttraumatic Stress Disorder) according to ICD-10. (International Statistical Classification of Diseases and Related Health Problems, 10th Revision). The exclusion criterion was prior psychiatric illness (traumatization before the war) and less than 8 years of education. All subjects received out-patient treatment. Their treatment involved psychopharmacological and psychotherapeutic therapy. The subjects were assessed using the following instruments: Sociodemographic Questionnaire designed by the authors for registering the social and demographic characteristics of the subjects (age, years of education, current employment, and socioeconomic status) and Manchester Quality of Life Scale (MANSA) as a self-report scale. The subjects were assessed prior to treatment, and three and six months after beginning the treatment (follow-up). Results: There was an increase in the mean values of subjective perception of Quality of Life between the first (3.2352), second (3.4447), and third test (3.6090). Differences between these mean values were not statistically significant between the first and second test, but significant between the second and third test. Also differences between sociodemographic characteristics prior to treatment and during six month follow-up were not statistically significant. A significant increase has been noted in the number of contacts with close friends between the first, second and third test. Also, we recorded a decrease in pertaining aggressive and criminal behavior between the three tests. Conclusion: The results of our study indicate that subjects who are suffering from chronic PTSD have a lower subjective perception of their quality of life. Combined psychopharmacological and psychotherapeutic treatment over a period of six months lead to improvement in the perception of quality of life. This may indicate the need for longer treatment of individuals suffering from chronic PTSD. A significant increase has been noted in the number of contacts with close friends between the first, second and third test, reflecting positive treatment effects on everyday life functioning and coping skills