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, ß=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.

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 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.

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

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.

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'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.

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.

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

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.

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

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.

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. 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.

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

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.

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.

Frequency of bipolar affective disorder in patients with major depressive episode with or without psychiatric co-morbid disorders.

BACKGROUND: Epidemiological studies indicate that only 20% of patients with Bipolar Affective Disorder are diagnosed on time while in 35% of patients diagnosis is 10 years late. Unipolar depression represents the most frequent misdiagnosis. AIM: The aim of this study was to determine the frequency of BAD in subjects diagnosed with Major Depressive Episode with or without co-morbid disorders. SUBJECTS: The study was a part of a large international, multi-center, non-interventional study that was conducted in 14 countries between May and November 2008. Sample in Bosnia and Herzegovina included 200 adult subjects with MDE according to the DSM IV diagnostic criteria who consented to take part in the study, who did not exhibit symptoms of acute somatic condition at the time, and who were capable of filling the HCL-32 checklist. METHODS: The following assessment instruments were used: CRF (Case Report Form) that includes general psychiatric assessment, GAF (Global Assessment of Functioning) and HCL-32 (Hypomania Symptom Checklist). RESULTS: Bipolar Affective Disorder was diagnosed in 67.84% of the study subjects, and MDE in 32.16%. At least one co-morbid psychiatric disorder was present in 77.78% of subjects with BAD and in 22.22% of subjects with MDE. Anxiety disorders co-morbidity was present in 61.9% of subjects with BAD and in 38.10% of subjects with MDE. CONCLUSIONS: Our results confirm previous research about underdiagnosing of BAD. This has unforeseen consequences on the course and prognosis of the disorder significantly affecting quality of life of the patients.

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.

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.

Venlafaxine efficacy and tolerability in the treatment of post-stroke depression.

OBJECTIVE: To determine the efficacy of venlafaxine in treatment of post-stroke depression. METHODS: The sample consisted of 30 adult subjects with symptoms of post-stroke depression. All subjects received treatment with venlafaxine in therapeutic dose range in the period of three months. All subjects were assessed prior to treatment and in 1 month-follow-up and 3 months follow-up using the standardized instruments for assessment of depressive symptoms (Hamilton Depression Rating Scale HAM-D-21), and for efficacy and tolerability with the Clinical Global Impressions scale (CGI). All subjects signed an informed consent form prior to entering in the study. RESULTS: The results indicate a statistically significant reduction of depressive symptoms following three months of treatment with venlafaxine. The difference between three assessments with The Clinical Global Impressions scale was statistically significant. Unwanted effects were registered in two of the subjects (increased blood pressure) and they were of mild intensity. CONCLUSIONS: Venlafaxine proved to be very efficient, well tolerated and safe in the treatment of depression occurring after cerebrovascular incidents to the subjects in this study.

Regional collaboration in reconstruction of mental health services in Bosnia and Herzegovina.

The war in the former Yugoslavia between 1991 and 1995 destroyed the mainly hospital-based mental health care system in Bosnia and Herzegovina. This report summarizes the situation before and after the war and describes efforts to rebuild and reform mental health services under politically and economically challenging conditions. As a result of these efforts, there are now 39 multidisciplinary community mental health centers that are linked to primary care and that aim to provide prevention, treatment, and rehabilitation of mental disorders. The reform process has been supported by international initiatives and is now continuing in collaboration with other countries in South Eastern Europe.

Torture victims and mechanisms of coping with stress.

The research has been performed over the torture victims during the aggression against Bosnia and Herzegovina. All patients-torture victims were of a different nationality as compared to the aggressors. The goal of the study was to register strategies of coping with stress in patients-torture victims before and after a three- month long treatment. All tested patients were psychologically tortured and physically abused. Strategies of coping with stress registered in tortured victims before the beginning of treatment and after a three-month combined psychotherapeutic and pharmacoterapeutic treatment. After completion of treatment, there was a significant increase in frequency of seeking social support, whereas accepting of responsibility was significantly decreased. Positive coping strategies like self-control, positive reinterpretation and planned problem-solving show a slight increase after the treatment, but the resu1ts are not significant.

Impact of war traumatic events on the socio-demographic characteristics of the civilian population in bosnia and herzegovina.

AIM: The aim of the present contribution is to present the socio-demographic characteristics of the torture survivors and specific life changes caused by the torture, and to create real assumptions for adequate socio-medical treatment. SUBJECTS AND METHODS: The present research was carried out in the Psychiatric clinic in Sarajevo with patients who were victims of torture during the aggression on Bosnia and Herzegovina, who were treated after the aggression for psychological and physical disorders. Socio-demographic data were collected by applying the specially constructed General Questionnaire consisting of 28 questions, prior to the psychiatric interview. After that a statistical analysis of the data collected was carried out.

Specific differences in trauma related symptoms between the refugees survivors of torture and refugees of war.

AIM: The aim of this study was to determine specific differences in trauma related symptoms in a group of subjects who were survivors of torture and displacement compared with a group of subjects who survived displacement as a consequence of state sponsored violence in Bosnia and Herzegovina. SUBJECTS: The subjects were divided in two groups of 50 adult survivors; one group comprising of 50 survivors of displacement and torture, the other group of 50 survivors of displacement who did not experience torture. The age range of the subjects was between 20 and 60. The groups were homogenous according to all other criteria. The exclusion criteria were prior psychiatric history and the experience of a loss of secondary family (spouse or child). METHODS: All subjects were assessed using the standardized multidimensional instrument for symptom assessment, SCL 90-R (L.R.Derogatis, 1986). Mississippi Questionnaire, (Keane et al. 1988), was used for assessment of symptoms of PTSD. Sociodemographic questionnaire designed by the authors was used for registering of the sociodemographic characteristics of the subjects. RESULTS: The results of our study show a statistically significant difference in trauma related symptoms between a group of subjects who were refugees with the experience of torture and a group of subjects who were refugees only. The symptoms of PTSD are increased in survivors of torture to a degree that is statistically significant compared with the presence of PTSD symptoms in a group of refugees. Anxiety, depression, somatization, obsessive-compulsive symptoms, phobic symptoms, hostility, interpersonal sensitivity, paranoid and psychotic symptoms are present to a statistically higher degree in a group of refugees survivors of torture than in the group of refugees. There is also a statistically significant difference between the groups in socio-economic status in the period after the war. Refugees survivors of torture have significantly worse socio-economic situation, probably due to impairment in social functioning in these subjects.

Specific differences in trauma related symptoms between war veterans and the civilian population.

AIM: The aim of this study was to determine specific differences in trauma related symptoms between the civilians who survived the trauma of war and veterans of war who have had the experience of combat stress. METHODS: The study involved two groups of subjects, with 50 male subjects in the age range between 20 and 50 in each group who had no psychiatric history prior to traumatization. All subjects were assessed for psychopathological symptoms using the multidimensional instrument for symptom assessment SCL 90-R (L.R. Derogatis 1986.). This instrument contains 90 articles divided in 9 subscales. PTSP symptoms were assessed with Mississippi Questionnaire designed by Keane et al 1988, and containing 35 articles. Sociodemographic characteristics were registered by the use of a special questionnaire designed by the authors. CONCLUSIONS: Our results indicate a statistically significant difference in the presence of symptoms between the two groups. Both PTSP and other related symptoms were present in statistically significant higher degree in the group of war veterans than in the group of civilian survivor of war traumas. There is also a statistically significant difference in socio-economic status in the period after the war between the two groups. This difference is at a disadvantage of the group of war veterans who are fairing significantly worse. This is probably due to the consequences of traumatization as well to secondary traumatization, absence of expected reward for their effort and impairment in social functioning in the group of war veterans.