Depression and stress levels in patients with different psychiatric disorders during concurrent early-phase COVID-19 pandemic and earthquake in Croatia.

BACKGROUND: While Croatia shared COVID-19 pandemic with other countries, its capital area was also hit by a 5.6 magnitude earthquake. The simultaneous impact of these two disasters on psychiatric patients is largely unknown, and we addressed those knowledge gaps. METHODS: The cross-sectional study was conducted during the pandemic's first peak, in the aftermath of earthquake, by telephonic survey. Measurements included the Patient Health Questionnaire-9, the Perceived Stress Scale and the semi-structured interview to evaluate the impact of pandemic stress and earthquake. Overall 396 patients with depression and/or anxiety disorders (DAD), 229 participants with schizophrenia spectrum disorders (SSD) and 205 healthy controls were enrolled. RESULTS: Both patient groups had higher depression and stress levels than controls, independent of sex, age and the presence of somatic comorbidity. After controlling for the same covariates, patient groups had higher COVID-19- and earthquake-related fears than controls. In patients with DAD, both fears were greater than among SSD patients. When comparing the two fears, the fear from earthquake was higher in DAD and control groups, whereas in SSD patients there was no such difference. CONCLUSIONS: Patients with DAD were the most vulnerable group during disasters, while earthquake seems to be associated with more fear than the pandemics, at least in DAD patients and healthy individuals. Future longitudinal studies should determine if early psychological support might alleviate stress levels after disasters and prevent further worsening of mental health, particularly among DAD patients.

Comorbidity among depression, anxiety and stress symptoms in naturalistic clinical samples: A cross-cultural network analysis.

Comorbidity between depression and anxiety is well-established across various settings and cultures. We approached comorbidity from the network psychopathology perspective and examined the depression, anxiety/autonomic arousal and stress/tension symptoms in naturalistic clinical samples from Serbia, Italy and Croatia. This was a multisite study in which regularized partial correlation networks of the symptoms, obtained via self-reports on the Depression Anxiety and Stress Scales-21 (DASS-21) in three cross-cultural, clinical samples (total N = 874), were compared with respect to centrality, edge weights, community structure and bridge centrality. A moderate degree of similarity in a number of network indices across the three networks was observed. While negative mood emerged to be the most central node, stress/tension nodes were the most likely bridge symptoms between depressive and anxiety/autonomic arousal symptoms. We demonstrated that the network structure and features in mixed clinical samples were similar across three different languages and cultures. The symptoms such as agitation, restlessness and inability to relax functioned as bridges across the three symptom communities explored in this study. Important theoretical and clinical implications were derived.

SUICIDE ATTEMPTS ARE ASSOCIATED WITH PERSONALITY DIMENSIONS IN CROATIAN WAR VETERANS WITH POSTTRAUMATIC STRESS DISORDER.

BACKGROUND: Patients with combat-related posttraumatic stress disorder (PTSD) have an increased frequency of suicide ideations, but also a higher risk of suicide attempts. Of all the known predisposing risk factors of suicide attempts in this population, personality dimensions are one of the least investigated. The main aim of this study was to examine if personality traits, namely temperament and character dimensions and trait impulsivity, are associated with suicide attempts in war veterans with PTSD. SUBJECTS AND METHODS: his sample included 178 Croatian male war veterans (mean age 49.20 years) treated for PTSD at the Department of Psychiatry and Psychological Medicine, University Hospital Center Zagreb. These patients were assessed with the M.I.N.I. diagnostic interview and they filled out several self-report scales: the Beck Depression Inventory-Second Edition (BDI-II), the Temperament and Character Inventory-Revised (TCI-R), the Barratt Impulsiveness Scale-11 (BIS-11), and the Satisfaction with Life Scale (SWLS). RESULTS: It was found that 42 (24%) Croatian war veterans with PTSD had a previous suicide attempt. Comparison between the two groups (participants with vs. those without history of suicide attempts) revealed that patients with previous suicide attempts are less educated and more often unemployed, have a longer duration of psychiatric treatment and more psychiatric hospitalizations, and exhibit higher levels of depression and lower life satisfaction. In multivariate logistic regression analyses, temperament dimension Harm Avoidance and character dimension Self-transcendence were unique predictors of suicide attempts, above the influence of age, education level and length of treatment. CONCLUSIONS: Croatian war veterans with PTSD have a substantial risk of suicide attempts. In addition to the role of some sociodemographic and clinical factors, it seems that certain personality dimensions are uniquely associated with suicide behaviours among these individuals.

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.

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.

Personality Organization and Depressive Symptoms Among Psychiatric Outpatients: The Mediating Role of Shame.

ABSTRACT: Previous research has demonstrated relations between lower level of personality organization (PO) and multiple indices of mental health disturbances. The goal of this research was to examine whether experience of shame would mediate the relationship between PO and depressive symptoms in a sample of 321 Croatian psychiatric outpatients (64% female; mean age, 38.67 years). The total PO level exhibited positive associations with depressive symptoms and with all three subscales of shame ( p < 0.01). Characterological, behavioral, and bodily shame showed significant mediating effects in the PO-depression relationship, while controlling for the influence of age and sex. PO level seems to be strongly related to depressive disturbances, with the experience of shame representing one of the underlying mechanisms of this relationship. Given that patients with personality disorders ( i.e. , low PO level) suffer from poorer treatment outcomes for major mental disorders, more emphasis should be placed on psychotherapeutic management of shame-proneness.

The Role of Psychological Factors in the Outcome of In Vitro Fertilization in Women with Primary Infertility.

INTRODUCTION: Infertility is a multidimensional developmental crisis of the individual, couple, family and the population as a whole. This study concentrates on the psychological aspects of infertility treatment by in vitro fertilization (IVF). The aim of this study was to examine a connection between certain psychological factors - anxiety, depression, motivation for parenthood, styles of coping with stress - and the outcome of IVF. SUBJECTS AND METHODS: The study included 100 primarily infertile women aged 23-38 years, who underwent IVF procedure for the first time, at the Department of Gynaecology and Obstetrics of University Hospital Centre Zagreb. Regarding the outcome of IVF, they were divided into two groups, those with positive outcome (N=50), and those with negative outcome of IVF (N=50). We have applied: general data questionnaire, Parenthood motivation scale, COPE Inventory, and Depression, Anxiety, Stress Scales - 21. RESULTS: The dimension of motivation for parenthood Relationship and the styles of coping with stress Seeking emotional support, Planning and Active coping proved to be statistically significant predictors of IVF outcome. By increasing the results on the relationship, seeking emotional support and planning subscales, the likelihood of negative outcome was increased. By increasing the results on the active coping subscale, the likelihood of positive outcome was increased. Anxiety and depression symptoms did not prove to be statistically significant predictors of the IVF outcome. CONCLUSION: The role of psychological factors is important for understanding the diagnosis and treatment of infertility. They also provide the basis for creating guidelines for specific preventive and educational programs and for special forms of psychological counselling for individuals facing infertility.

Symptom continuum reported by affective disorder patients through a structure-validated questionnaire.

BACKGROUND: Affective disorders, such as major depressive (MDD), bipolar I (BD I) and II (BD II) disorders, are overlapped at a continuum, but their exact loci are not clear. The self-reports from patients with affective disorders might help to clarify this issue. METHODS: We invited 738 healthy volunteers, 207 individuals with BD I, 265 BD II, and 192 MDD to answer a 79 item-MATRIX about on-going affective states. RESULTS: In study 1, all 1402 participants were divided random-evenly and gender-balanced into two subsamples; one subsample was used for exploratory factor analysis, and another for confirmatory factor analysis. A structure-validated inventory with six domains of Overactivation, Psychomotor Acceleration, Distraction/ Impulsivity, Hopelessness, Retardation, and Suicide Tendency, was developed. In study 2, among the four groups, MDD scored the highest on Retardation, Hopelessness and Suicide Tendency, whereas BD I on Distraction/ Impulsivity and Overactivation. CONCLUSION: Our patients confirmed the affective continuum from Suicide Tendency to Overactivation, and described the different loci of MDD, BD I and BD II on this continuum.

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

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.

Personality and Stigma in Lung Cancer Patients.

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.

COVID-19 Pandemia and Public and Global Mental Health from the Perspective of Global Health Securit.

The Coronavirus disease 2019 (COVID-19) pandemic emerged in Wuhan, China and has spread all over the world and has caused huge threats to health and lives. It has affected different frontiers of lives and induced many psychiatric individual and collective problems such as panic, anxiety, depression, post-traumatic stress disorders, suspiciousness, infodemia, cacophony, xenophobia, racisms, etc. The COVID-19 outbreak has induced public and global mental health crisis as well as a huge psycho-social experiment. Psychiatry and other mental health sciences can play very useful role in supporting the well-being of COVID-19 patients and their families, healthcare personnel and the society. For successful fighting with present and future pandemics we have to learn more about psychiatric and psychological aspects of COVID-19 from the perspectives of public and global mental health.

The Importance of Psychodynamic Approach during COVID-19 Pandemic.

The coronavirus (COVID-19) outbreak was labeled a global pandemic by the WHO in March of 2020. Understanding how crisis influence an individual's reactions to stressful events (and vice versa) is important in order to create meaningful and effective interventions. Our literature search have revealed lack of the papers related to psychodynamic approach to recent crisis. Psychodynamic places a large emphasis on defense mechanisms and unconscious mind, where upsetting feelings, urges, and thoughts that are too painful for us to directly look at are housed. Even though these painful feelings and thoughts are outside of our awareness, they still influence our behavior in many ways. Optimal application of psychodynamic approach offers the frame for acceptance of psychological stress in a more positive way and benefits psychological growth. We believe that including psychodynamic approach in the national public and mental health emergency system will empower Croatia and the world during (and after) COVID-19 pandemic crisis.

Pathological Narcissism, Negative Parenting Styles and Interpersonal Forgiveness among Psychiatric Outpatients.

BACKGROUND: Pathological narcissism has previously been investigated with regard to negative parenting and interpersonal forgiveness, but inconsistent findings have been obtained in relation to its two phenotypic forms - grandiosity and vulnerability. Moreover, the role of negative parenting in the lack of forgiveness within narcissistic pathology has not been explored thus far. The aim of the current research was to investigate the complex relations among pathological narcissism, negative parenting, and interpersonal forgiveness in psychiatric outpatients. SUBJECTS AND METHODS: A sample of 250 adult psychiatric outpatients (61% female; mean age 39.15 years) were enrolled in this study. The participants filled out the Pathological Narcissism Inventory (PNI), the Tendency to Forgive Scale (TTF), the Measure of Parental Styles (MOPS), and the Depression, Anxiety, Stress Scales (DASS21). RESULTS: Narcissistic grandiosity and narcissistic vulnerability were positively correlated with mothers' and fathers' negative parenting, but this association was significantly stronger in the case of narcissistic vulnerability. Only narcissistic vulnerability was related to interpersonal forgiveness. In the mediation analysis, negative parenting was not directly related to interpersonal forgiveness, however, this association became significant after introducing narcissistic vulnerability. Narcissistic vulnerability served as a full mediator of the mothers' and fathers' negative parenting - interpersonal forgiveness relationships. CONCLUSIONS: Narcissistic vulnerability seems to be more strongly related to negative parenting and interpersonal forgiveness than narcissistic grandiosity, while it also represents one of the underlying mechanisms of the negative parenting - interpersonal forgiveness relationship. The clinical implications of these findings are discussed in relation to pathological narcissism and lack of forgiveness.

Utilization of somatic healthcare in Croatian patients with schizophrenia spectrum disorder, major depression, PTSD and the general population.

BACKGROUND: Utilization of somatic healthcare services is highly predictive of the development of chronic physical illnesses and increased mortality risks. The objective of this study was to assess the differences in healthcare utilization among patients with schizophrenia spectrum disorders (SSD), major depressive disorder (MDD) and posttraumatic stress disorder (PTSD) and the general population in Croatia. METHODS: We enrolled 566 Croatian participants from the general population, 282 with SSD, 178 with MDD, and 86 with PTSD. The primary outcome was a self-reported specialist consultation for non-psychiatric (e.g., somatic) causes within the previous 12 months. RESULTS: Although SSD patients with chronic physical illnesses were significantly more often hospitalized for physical illness than the general population, the proportion of patients who had a specialist consultation were equal in SSD and the general population. MDD and PTSD patients had significantly higher adjusted odds for specialist consultation than the general population and SSD patients (MDD compared to SSD: OR = 2.14; 95% CI 1.27-3.59; PTSD compared to SSD: OR = 2.03; 95% CI 1.00-4.10). CONCLUSIONS: SSD patients' utilization of somatic healthcare is equal to the general population, despite their increased healthcare needs. However, their utilization is lower than in MDD and PTSD patients and, therefore, probably not adequate. TRIAL REGISTRATION: The study protocol was registered at ClinicalTrials.gov ( NCT02773108 ) on May 16, 2016.

Anhedonia in Schizophrenia: Mini-Review.

The perception of reward exerts a powerful influence on human behavior. While anhedonia might occur in healthy individuals, its prevalence and severity are much higher in psychiatric patients, particularly those with depression and schizophrenia. Anhedonia is a negative symptom, and presumably a trait marker in schizophrenia. Recent research confirmed that anhedonia is a complex construct, consisting of anticipatory, consummatory, and reward learning components. In general, schizophrenia patients show anticipation deficits, and a substantial portion of them have physical (PA) and social anhedonia (SA). The relationship between anhedonia and psychopathology appears bidirectional. While gene-environment interactions affect reward circuity, anhedonia modulates clinical features, such as suicidality and nicotine consumption. Future clinical research employing longitudinal designs may shed more light on the dynamics and treatment of anhedonia in schizophrenia.

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.