Rare copy number variation in posttraumatic stress disorder.

Posttraumatic stress disorder (PTSD) is a heritable (h2 = 24-71%) psychiatric illness. Copy number variation (CNV) is a form of rare genetic variation that has been implicated in the etiology of psychiatric disorders, but no large-scale investigation of CNV in PTSD has been performed. We present an association study of CNV burden and PTSD symptoms in a sample of 114,383 participants (13,036 cases and 101,347 controls) of European ancestry. CNVs were called using two calling algorithms and intersected to a consensus set. Quality control was performed to remove strong outlier samples. CNVs were examined for association with PTSD within each cohort using linear or logistic regression analysis adjusted for population structure and CNV quality metrics, then inverse variance weighted meta-analyzed across cohorts. We examined the genome-wide total span of CNVs, enrichment of CNVs within specified gene-sets, and CNVs overlapping individual genes and implicated neurodevelopmental regions. The total distance covered by deletions crossing over known neurodevelopmental CNV regions was significant (beta = 0.029, SE = 0.005, P = 6.3 × 10-8). The genome-wide neurodevelopmental CNV burden identified explains 0.034% of the variation in PTSD symptoms. The 15q11.2 BP1-BP2 microdeletion region was significantly associated with PTSD (beta = 0.0206, SE = 0.0056, P = 0.0002). No individual significant genes interrupted by CNV were identified. 22 gene pathways related to the function of the nervous system and brain were significant in pathway analysis (FDR q < 0.05), but these associations were not significant once NDD regions were removed. A larger sample size, better detection methods, and annotated resources of CNV are needed to explore this relationship further.

Association of Tumor Necrosis Factor-Alpha with Psychopathology in Patients with Schizophrenia.

We investigated the relationship between serum tumor necrosis factor-alpha (TNF-α) levels and psychopathological symptoms, clinical and socio-demographic characteristics and antipsychotic therapy in individuals with schizophrenia. TNF-α levels were measured in 90 patients with schizophrenia and 90 healthy controls matched by age, gender, smoking status, and body mass index. The Positive and Negative Syndrome Scale (PANSS) was used to assess the severity of psychopathology in patients. No significant differences in TNF-α levels were detected between the patients and controls (p=0.736). TNF-α levels were not correlated with total, positive, negative, general, or composite PANSS scores (all p>0.05). A significant negative correlation was observed between TNF-α levels and the PANSS cognitive factor (ρ=-0.222, p=0.035). A hierarchical regression analysis identified the cognitive factor as a significant predictor of the TNF-α level (beta=-0.258, t=-2.257, p=0.027). There were no significant differences in TNF-α levels among patients treated with different types of antipsychotics (p=0.596). TNF-α levels correlated positively with the age of onset (ρ=0.233, p=0.027) and negatively with illness duration (ρ=-0.247, p=0.019) and antipsychotic treatment duration (ρ=-0.256, p=0.015). These results indicate that TNF-α may be involved in cognitive impairment in schizophrenia, and would be a potential clinical-state marker in schizophrenia.

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 Traits and Health Related Quality of Life in Patients with Irritable Bowel Sindrome and Inflammatory Bowel Disease.

BACKGROUND: Personality traits as alexithymia and type D personality may impair health related quality of life (HRQoL) in patients with irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD). Aim of this study was to evaluate personality traits in patients with IBS and IBD and their impact on HRQoL. MATERIALS AND METHODS: The subjects (40 patients with IBS, 40 with IBD and 40 health control subjects) completed SF-36 questionnaire, TAS-20 and DS14 scale. RESULTS: Patients with IBS and IBD had higher results on TAS-20 and DS14 scale when compared with healthy controls. Also IBS patients had higher scores than IBD patients. Higher scores on TAS-20 and DS14 scales in IBS and IBD patients correlate with lower HRQoL. HRQoL was poorer in IBS and IBD patients than in healthy control subjects. CONCLUSIONS: Alexithymia and type D personality in IBS and IBD patients are associated with lower HRQoL and psychological interventions should be considered.

Association between Resilience and Quality of Life in Patients with Colon Cancer.

INTRODUCTION: Colon cancer is one of the most common malignancies. Numerous studies suggest an association between resilience and quality of life in colon cancer patients. The aim of this study was to explore the association between resilience and quality of life in people with colon cancer. SUBJECTS AND METHODS: A cross-sectional study was conducted on a sample of 200 subjects at the Oncology Clinic of the University Clinical Hospital Mostar. Data were collected in the period between April 2019 and June 2021. A socio-demographic questionnaire specifically designed for this study, a CD-RISC-25 scale for assessing resilience, and a WHOQOL-BREF questionnaire for assessing quality of life were used for collecting data. RESULTS: A statistically significant positive association of resilience with all domains of quality of life was found. The mental health domain contributed the most statistically significantly positively to the level of resilience. Patients who were not married had a statistically significantly higher level of resilience compared to married, divorced and widowed patients. No statistically significant difference was found in resilience levels relative to other socio-demographic factors and cancer stage. Patients treated with a combination of surgery and chemotherapy had a statistically significantly higher level of resilience compared to patients treated with other therapeutic methods. CONCLUSIONS: Higher level of resilience statistically significantly contributes to a higher level of quality of life in people with colon cancer.

Anxiety of Patients at Magnetic Resonance Imaging Screening.

INTRODUCTION: Anxiety is a state of feeling helpless and insecure, a state of anticipation and concern that something bad will happen. Fear of pain and the unknown, as well as fear of screening results can increase anxiety. Severe anxiety during magnetic resonance imaging (MRI)can cause patient's movement, leading to poorer imaging and reduction in the quality of the diagnostic test. To determine the anxiety of patients before and after magnetic resonance imaging and to investigate the relationship between the tested anxiety and the socio-demographic characteristics of the patients. METHODS: The study was conducted at the Department of Radiology of the University Clinical Hospital Mostar in the period from February 1st 2020 to March 31st 2020. The study included 100 subjects who were prescribed an MRI screening at the time of the study. A socio-demographic questionnaire specifically designed for this study was used to obtain data on subjects such as gender, age, place of residence, smoking, drinking alcohol, economic status, religiosity. The Anxiety Questionnaire as a State-Trait Anxiety Inventory (STAI) was used to examine anxiety. RESULTS: A statistically significantly higher degree of anxiety was determined after MRI screening (p<0.001). Male subjects achieved a statistically significantly higher degree of anxiety before (p=0.019) and after (p=0.034) MRI screening. There were no statistically significant correlations between the age of the subjects and the results achieved on the anxiety tests before and after the MRI screening. CONCLUSION: Subjects who were prescribed an MRI screening have a statistically significantly higher degree of anxiety after the screening. Male subjects had a statistically significantly higher degree of anxiety on MRI screening.

Resilience and Quality of Life of Patients with Breast Cancer.

INTRODUCTION: Breast cancer is the most common malignancy in women. Modern research attempts to investigate the relationship between psychoemotional parameters and the length of survival of breast cancer patients. Understanding the factors which affect a higher level of resilience can have important clinical implications and can represent a guiding principle for designing psychological interventions that would accelerate recovery and improve the quality of life of cancer patients. To explore the relationship between resilience and quality of life of women with breast cancer. METHODS: The study was conducted at the Clinic of Oncology of the University Clinical Hospital Mostar, which included 60 subjects. Objective realization was achieved through using the socio-demographic questionnaire purposely made for this research, the quality of life questionnaire WHQOL-BREF and the psychological resilience questionnaire CD-RISC-25. RESULTS: Subjects treated with radiotherapy achieved statistically significantly higher scores on subscales of the quality of life: mental health, social relations, and the environment. No statistically significant correlations were found between the level of resilience and results in the domains of quality of life. CONCLUSION: There is not a statistically significant association between resilience levels and quality of life in patients with breast cancer.

Clinical evaluation of psychiatric and behavioral disorders in adolescents with epilepsy: a cross-sectional study.

Background: Epilepsy is a neurological disease that is often associated with psychiatric comorbidities.Subjects and methods: The aim of the study was to examine the frequency of psychic symptoms and their association with different types of epilepsy in the adolescent population. The study involved 100 adolescents with epilepsy and 100 healthy adolescents of both sexes at the age of 13-19. The examinees completed a standardized Symptom Checklist-90-R (SCL-90-R) questionnaire, concerning self-assessment of psychological disorders in the previous week. The value system of ​​nine dimensions and three global indexes of SCL-90-R scales were analyzed.Results: Our results suggest that adolescents with epilepsy have more than one psychic disorder compared to a healthy group of respondents. Somatic symptoms are more common in non-epileptic subjects, while obsessive-compulsive, depressive and phobic symptoms, as well as anxiety, aggressiveness, interpersonal vulnerability and paranoia, are more common in adolescents with epilepsy. Due to the type of epilepsy, obsessive compulsive symptoms are more common in adolescents with focal epilepsy, while the symptoms of phobia are more present in those with generalized epilepsy. The depth and intensity of psychological stress is higher in the group of adolescents with epilepsy compared to the healthy group of respondents.Conclusions: Psychiatric comorbidity is very common in epileptic patients and depending on the type of diagnosed epilepsy, various symptoms are expressed. Furthermore, psychological stress is more observable in adolescents with epilepsy. For patients with epilepsy, mental health care and seizure control is extremely important in the prevention of serious mental disabilities.

Correlation of Religiousness with the Quality of Life and Psychological Symptoms in Oncology Patients.

INTRODUCTION: Malignant diseases are one of the leading mortalities in the world, causing a range of psychological symptoms and reducing the quality of life in oncology patients. Examine the correlation of religion with the quality of life and psychological symptoms in oncology patients. SUBJECTS AND METHODS: The cross-sectional study included 100 oncology patients in the test group and 80 internal medicine patients in the control group. A sociodemographic questionnaire was specifically designed for this study, the Duke University Religion Index, the Symptom Check List 90, and the WHOQOL-100 quality of life assessment were used to collect the data. RESULTS: The average score in oncology patients was significantly lower on the subscales for physical health (p<0.000), social connections (p<0.002), and intrinsic religiousness (p<0.046) in comparison to internal medicine patients. On the psychological symptoms scale, the average score was higher in oncology patients with the largest difference observed on the psychoticism subscale (p<0.078). CONCLUSION: Oncology patients are statistically less religious and are not satisfied with the quality of life in comparison to internal medicine patients. Psychological symptoms are more pronounced in oncology patients but the difference is not statistically significant. A lower level of religiousness is statistically negatively correlated with a higher severity of psychological symptoms.

The Social Characteristics of Patients with Alcohol Use Disorder in the Area of the Tuzla Canton - Bosnia and Herzegovina.

BACKGROUND: Researches to date had indicated that socioeconomic status is a strong predictor of health behavior but also it has two-way effect with alcohol use disorder. This study examines social factors and their impact on alcohol use disorder and places individual alcohol use in the context of the status and conditions in which people live. To determine the distribution and characteristics of social factor in patients with alcohol use disorder (AUD) in the area of the Tuzla Canton (TC) in the period 01.01.2011 - 31.12.2015, in relation to: age, sex, marital status, level of education, municipality of residence, home ownership status, family structure, employment status, and monthly monetary income. SUBJECTS AND METHODS: Retrospective research was conducted using a systematic sample of 1863 patients with AUD, using documentation from the Psychiatry clinic of the University Clinical Centre (UCC) and the protocols of Health Centres. RESULTS: The sample was composed 1808 (97.05%) men and 55 (2.95%) women; the ratio of men to women was 33:1. the ages of the patients in the sample were 54.4±9.79 years - men 54.49±9.74 years; women 51.45±10.94 years. Most of the men in the sample were married (71.1%) and most of the women were widowed (54.5%). The largest number of patients had elementary school education (66.5%), were unemployed (56.8%), with a monthly monetary income less than 300 convertible marks (KM) (62.2%), owned their own home (78.2%), and 36.1% of them lived with a partner or their own children. CONCLUSIONS: There are significantly more men being treated for AUD; most of them are married, and most of the women are widowed. The largest number of patients treated for AUD have elementary school education, are unemployed, have monthly monetary income less than 300 km, own their own house, and a little more than one third of them lived with their partner or their own children.

The Personality of the Alcoholic through Seven Perspectives.

The different personalities of alcoholics are expressed in the way they manifest certain traits of their personality. In addition to knowing the general and common characteristics of alcoholics, it is even more important for clinical practice to know the differences between them, thus allowing a personalized approach to each patient, as a unique personality. The division of the personalities of alcoholics may be viewed through the prism of seven perspectives: the disease perspective, the dimensional perspective, the cognitive-anxiety perspective, the behavioral perspective, the spiritual/transcendent perspective, the narrative and the systemic perspective. Each of these perspectives more clearly represents part of the personality of the alcoholic; together they give a clearer picture of the problem and accordingly offer different treatment options.

Mental Health and Self-Esteem of Active Athletes.

INTRODUCTION: Systematic and continuous physical exercise of certain intensity and volume is irreplaceable in the stages of growth and development and in preventing impairments of the biological, functional and health state of the human organism.Many studies show that physical exercise contributes to development and reinforcement of mental health and increases self-esteem. Examine mental health and self-esteem of active athletes. SUBJECTS AND METHODS: The subjects of the study are active athletes from Herzegovina and students of the Faculty of Health Studies in Mostar. Mental health and self-esteem were measured by a sociodemographic questionnaire, The Symptom Checklist-90 and the Satisfaction With Life Scale. RESULTS: There is a statistically significant difference in the frequency of exercise, active athletes have the highest percentage (100%) and state that they exercise often (almost every day) while university students have a significantly lower percentage (20%).Students scored significantly higher on the subscales for somatization, obsessive - compulsive symptoms, interpersonal vulnerability, depression, anxiety, aggression, phobia, and paranoia than active athletes. Active athletes have statistically higher scores for almost all the claims of the subjective assessment of life satisfaction. CONCLUSION: Active athletes showed significantly less psychological symptoms and better mental health, greater life satisfaction and higher self-esteem than students of the Faculty of Health Studies in Mostar.

Psychic Symptoms and Self-Esteem in Dancers.

INTRODUCTION: The mental health of the human being and a higher level of the self-esteem have the positive effects on the peace surrounding, stability, success and the personal satisfaction of any individual. The fundamental opinion is that the dance has the affect on the body and the psychical health of the people. To explore if the dancers have their less-expressed psychical symptoms and higher self-esteem. SUBJECTS AND METHODS: The examination was performed on the sample of 310 examinees, mostly of the young life age and who identified themselves as the dancers or non-dancers. For the requirements of the investigation there were used the socio-demographic question-form, the psychical symptoms estimation scale (RCL-90-R) and the Rosenberg self-esteem scale (RSES). RESULTS: The dancers show the smaller appearance of the psychical symptoms and that almost in all sub-scales, but their difference is not statistically significant. The statistically significant difference among the men and the women was recorded in the subscales of the somatisations, then the interpersonal vulnerability, the depression, the anxiety and the phobias. The dancers possess their higher self-esteem then the non-dancers, but statistically their difference is not significant. Comparing the results against the sex, the persons of the female sex possess the higher self-respect than the persons of the male sex. CONCLUSION: The dancers possess less of the psychical symptoms and their higher self-esteem than the non-dancers, but the difference within the results is not significant statistically.

HIV prevalence, knowledge and self-perceived risk of HIV infection among tuberculosis patients in Serbia.

OBJECTIVE: The aim of the study was to estimate the seroprevalence of HIV infection among TB patients, knowledge, self-perceived risks and testing practices related to HIV. METHODS: We performed cross-sectional study from 10 May to 15 July 2011. Cluster sampling method was used to select 27 hospitals where 289 TB patients were consecutively recruited. Descriptive statistics and multivariable logistic regression methods were used to identify the factors associated with correct comprehensive knowledge of HIV/AIDS. RESULTS: HIV prevalence among TB patients was 0.3%. Only 25.2% of the respondents presented comprehensive correct knowledge of HIV/AIDS. The percentage of correct answers to all questions related to knowledge about HIV/AIDS increases with educational status (χ2 = 5.42; p < 0.05) and decreases with the age of respondents (χ2 = 8.53; p > 0.05). The independent predictors of correct comprehensive knowledge were living without partner (OR = 4.45; CI = 1.59-12.95) and self-awareness of HIV risk (OR = 4.43; CI = 1.20-16.52). CONCLUSION: HIV prevalence among TB patients is higher than among general population in Serbia. The level of comprehensive correct knowledge of HIV/AIDS is low. There is a need for continuous implementation of public health strategy to successfully manage HIV and HIV/TB co-infection in Serbia.

Workplace Stress in the University Clinical Settings: Comparison between the Cardiac Unit snd Emergency Center Medical Staff.

BACKGROUND: Stress at work is a specific type of stress arising from the work environment. Stress of the medical staff has been investigated in recent years by the medical institutions of different countries. The aim of this study was to examine the stress levels in medical staff of Department of Cardiac Surgery and Center of emergency medicine (CEM) in the Clinical settings, and to compare them. SUBJECTS AND METHODS: We conducted a cross-sectional study which included 55 patients between 21 and 50 years of age. The study group consisted of 30 employees from the Department of Cardiac Surgery of Mostar University Clinical Hospital, while the control group comprised 25 employees from the CEM. Research instruments were the Occupational Stress Questionnaire for Hospital Health Care Workers (OSQ-HHCW), General Health Questionnaire (GHQ 28) and a Stress MGMT-TEST A. RESULTS: The subjects from the control group had significantly higher stress experience in "bombing" with new information (p=0.028), unavailability of literature (p=0.039), poor communication with superiors (p<0.001), conflicts with patients (p=0.042) and inappropriate public criticism (p=0.007). The highest stress level showed F1 group of stressors, concerning the organization of work and funding. CEM employees had statistically significantly higher level of stress on public criticism and lawsuits compared to the study group (p=0.013), as well as higher score on the anxiety/insomnia subscale (p<0.001), social dysfunction scale (p=0.002) and on the depression subscale (p<0.001). CONCLUSIONS: Stressors from the group of organizational factors have proven to be the most common stressors in both groups. However, in some areas within the impact of workplace stress, CEM employees had significantly greater vulnerability compared to employees of the Department of cardiac surgery. Further studies are needed to establish the frequency and intensity of stress among health professionals, and to clearly determine the risk factors for its development.

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.