Posttraumatic stress disorder (PTSD) is a heritable (h2 = 24–71%) psychiatric illness. Copy numbe... more 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. Th...
Objectives Posttraumatic stress disorder (PTSD) is triggered by extremely stressful environmental... more 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 PT...
Sexual functioning of war veterans is significantly under-explored. During devastating aggression... more Sexual functioning of war veterans is significantly under-explored. During devastating aggression on Bosnia-Herzegovina (BiH) around 400 thousand soldiers were included in combats. It is estimated that more than 100 000 persons were killed, and more than 60 000 them were soldiers. Vast majority of them were deployed since war is ended. We found high prevalence of sexual dysfunctions in war veterans. Also significant difference in several areas of sexual functioning between war veterans with and without symptoms of posttraumatic stress disorder was found.
Study ObjectivesSleep problems are common, serving as both a predictor and symptom of posttraumat... more Study ObjectivesSleep problems are common, serving as both a predictor and symptom of posttraumatic stress disorder (PTSD), with these bidirectional relationships well established in the literature. While both sleep phenotypes and PTSD are moderately heritable, there has been a paucity of investigation into potential genetic overlap between sleep and PTSD. Here, we estimate genetic correlations between multiple sleep phenotypes (including insomnia symptoms, sleep duration, daytime sleepiness, and chronotype) and PTSD, using results from the largest genome-wide association study (GWAS) to date of PTSD, as well as publicly available GWAS results for sleep phenotypes within UK Biobank data (23 variations, encompassing four main phenotypes).MethodsGenetic correlations were estimated utilizing linkage disequilibrium score regression (LDSC), an approach that uses GWAS summary statistics to compute genetic correlations across traits, and Mendelian randomization (MR) analyses were conducted...
The risk of posttraumatic stress disorder (PTSD) following trauma is heritable, but robust common... more The risk of posttraumatic stress disorder (PTSD) following trauma is heritable, but robust common variants have yet to be identified. In a multi-ethnic cohort including over 30,000 PTSD cases and 170,000 controls we conduct a genome-wide association study of PTSD. We demonstrate SNP-based heritability estimates of 5–20%, varying by sex. Three genome-wide significant loci are identified, 2 in European and 1 in African-ancestry analyses. Analyses stratified by sex implicate 3 additional loci in men. Along with other novel genes and non-coding RNAs, a Parkinson’s disease gene involved in dopamine regulation, PARK2, is associated with PTSD. Finally, we demonstrate that polygenic risk for PTSD is significantly predictive of re-experiencing symptoms in the Million Veteran Program dataset, although specific loci did not replicate. These results demonstrate the role of genetic variation in the biology of risk for PTSD and highlight the necessity of conducting sex-stratified analyses and exp...
Bosnia and Herzegovina (BH) is located on the western part of the Balkan Peninsula. It has an are... more Bosnia and Herzegovina (BH) is located on the western part of the Balkan Peninsula. It has an area of 51 210 km2 and a population of 3 972 000. According to the Dayton Agreement of November 1995, which ended the 1992-95 war, BH comprises two ‘entities’ - the Federation of Bosnia and Herzegovina (FBH) and the Republic of Srpska (RS) - and the District of Brcko. The administrative arrangements for the management and financing of mental health services reflect this. The FBH, with 2 325 018 residents, is a federation of 10 cantons, which have equal rights and responsibilities. The RS has 1 487 785 residents and, in contrast, a centralised administration. Brcko District has just under 80 000 residents.
Post-traumatic stress disorder (PTSD) is a common and debilitating disorder. The risk of PTSD fol... more Post-traumatic stress disorder (PTSD) is a common and debilitating disorder. The risk of PTSD following trauma is heritable, but robust common variants have yet to be identified by genome-wide association studies (GWAS). We have collected a multi-ethnic cohort including over 30,000 PTSD cases and 170,000 controls. We first demonstrate significant genetic correlations across 60 PTSD cohorts to evaluate the comparability of these phenotypically heterogeneous studies. In this largest GWAS meta-analysis of PTSD to date we identify a total of 6 genome-wide significant loci, 4 in European and 2 in African-ancestry analyses. Follow-up analyses incorporated local ancestry and sex-specific effects, and functional studies. Along with other novel genes, a non-coding RNA (ncRNA) and a Parkinson’s Disease gene,PARK2, were associated with PTSD. Consistent with previous reports, SNP-based heritability estimates for PTSD range between 10-20%. Despite a significant shared liability between PTSD and ...
The international journal of neuropsychopharmacology, Jan 23, 2017
Posttraumatic Stress Disorder (PTSD) is characterized by an overactive noradrenergic system confe... more Posttraumatic Stress Disorder (PTSD) is characterized by an overactive noradrenergic system conferring core PTSD symptoms such as hyperarousal and re-experiencing. Monoamine oxidase A (MAO-A) is one of the key enzymes mediating the turnover of noradrenaline. Here, DNA methylation of the MAOA gene exonI/intronI region was investigated for the first time in regards to its role in PTSD risk and severity. MAOA methylation was analyzed via direct sequencing of sodium bisulfite treated DNA extracted from blood cells in a total sample of N=652 (m=441) patients with current PTSD, patients with remitted PTSD and healthy probands (comparison group) recruited at five centres in Bosnia-Herzegovina, Croatia, and the Republic of Kosovo. PTSD severity was measured by means of the Clinician-Administered PTSD Scale (CAPS) and its respective subscores representing distinct symptom clusters. In the male, but not the female sample, patients with current PTSD displayed hypermethylation of three CpGs (Cp...
IntroductionAlexithymia consider a cluster of cognitive and affective characteristics that includ... more IntroductionAlexithymia consider a cluster of cognitive and affective characteristics that include: inability of recognizing and describing emotions, difficulties in distinguishing feelings and physical sensations during emotional arousal, narrowed capacity for imagination and externally oriented cognitive style. Several studies links alexithymia with increased risk for physical and mental damage. Symptoms of alexithymia are documented in persons who develop PTSD in response to different types of traumatic events.ObjectivesTo examine alexithymia in war veterans.AimsTo determine whether alexithymia is significantly more present in war veterans with PTSD.MethodsCross-sectional study of 205 war veterans tested by Harvard Trauma Questionnaire and by Toronto Alexithymia Scale (TAS-20).ResultsOut of 205 war veterans 89 (43.4%) of them have alexithymia. Significantly more veterans with PTSD (78 or 75%) than without PTSD (11 or 10.9%) has alexithymia (Chi2 = 88.955, P < 0.001) was found ...
To establish the prevalence of metabolic syndrome and its parameters in group of patients with sc... more To establish the prevalence of metabolic syndrome and its parameters in group of patients with schizophrenia in polypharmacy - receiving first generation antipsychotics versus clozapine alone treated group. 48 outpatients with schizophrenia divided into two groups: the first group of 21 patients in polypharmacy with first generation antipsychotics, and the second group of 27 patients treated with clozapine alone were assessed for the presence of metabolic syndrome. We used logistic regression models to assess the relationship between metabolic syndrome and antipsychotic therapy, gender and age. Metabolic syndrome was found in 52.1% of all subjects. Compared to first generation antipsychotics polypharmacy, the monopharmacy with clozapine was associated with elevated rates of metabolic syndrome (28.6% vs. 70.4%, p=0.004). With regard to particular parameters of metabolic syndrome, the elevated plasma triglycerides were significantly more present in subjects within Clozapine group (p=0...
The aim was to analyse contacts network and satisfaction with contacts among children of parents ... more The aim was to analyse contacts network and satisfaction with contacts among children of parents with post traumatic stress disorder (PTSD). The sample consisted of 100 pupils (age 10 to 15) from two randomly chosen schools. Children were selected from general population, lived with both parents who have had war traumatic experiences. They agreed to participate in psychometric research. We divided them in two groups: observed (0) group of children (N=50) whose parents were showing symptoms of post traumatic stress disorder (PTSD) and control (C) group of children (N=50) whose parents did not show symptoms of PTSD (evaluated by Harvard trauma questionnaire-BiH version). Contact network was examined by a Map of Contact Network which includes contact and satisfaction with persons in close environment. In relation to gender representatives of fathers and mothers, sample was homogenous. The most important persons in children whose parents are showing symptoms of PTSD were schoolmates (88...
Background: To establish the prevalence of metabolic syndrome and its parameters in group of pati... more Background: To establish the prevalence of metabolic syndrome and its parameters in group of patients with schizophrenia in polypharmacy – receiving first generation antipsychotics versus clozapine alone treated group. Subjects and methods: 48 outpatients with schizophrenia divided into two groups: the first group of 21 patients in polypharmacy with first generation antipsychotics, and the second group of 27 patients treated with clozapine alone were assessed for the presence of metabolic syndrome. We used logistic regression models to assess the relationship between metabolic syndrome and antipsychotic therapy, gender and age. Results: metabolic syndrome was found in 52.1% of all subjects. Compared to first generation antipsychotics polypharmacy, the monopharmacy with clozapine was associated with elevated rates of metabolic syndrome (28.6% vs. 70.4%, p= 0.004). With regard to particular parameters of metabolic syndrome, the elevated plasma triglycerides were significantly more present in subjects within Clozapine group (p=0.03). Logistic regression analysis showed that female gender (p= 0.004), older age (p=0.56), and clozapine treatment (p= 0.005) were significantly associated with metabolic syndrome. Discussion: Results of this study are consistent with other studies, which showed that patients receiving Clozapine are at higher risk for metabolic abnormalities. Conclusion: Compared to polypharmacy with first generation antipsychotics, the higher prevalence of metabolic syndrome is found in patients treated with Clozapine alone. The most prevalent metabolic disorder is dyslipidemia. Female gender, older age, clozapine treatment are significantly associated with metabolic syndrome.
Posttraumatic stress disorder (PTSD) is a heritable (h2 = 24–71%) psychiatric illness. Copy numbe... more 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. Th...
Objectives Posttraumatic stress disorder (PTSD) is triggered by extremely stressful environmental... more 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 PT...
Sexual functioning of war veterans is significantly under-explored. During devastating aggression... more Sexual functioning of war veterans is significantly under-explored. During devastating aggression on Bosnia-Herzegovina (BiH) around 400 thousand soldiers were included in combats. It is estimated that more than 100 000 persons were killed, and more than 60 000 them were soldiers. Vast majority of them were deployed since war is ended. We found high prevalence of sexual dysfunctions in war veterans. Also significant difference in several areas of sexual functioning between war veterans with and without symptoms of posttraumatic stress disorder was found.
Study ObjectivesSleep problems are common, serving as both a predictor and symptom of posttraumat... more Study ObjectivesSleep problems are common, serving as both a predictor and symptom of posttraumatic stress disorder (PTSD), with these bidirectional relationships well established in the literature. While both sleep phenotypes and PTSD are moderately heritable, there has been a paucity of investigation into potential genetic overlap between sleep and PTSD. Here, we estimate genetic correlations between multiple sleep phenotypes (including insomnia symptoms, sleep duration, daytime sleepiness, and chronotype) and PTSD, using results from the largest genome-wide association study (GWAS) to date of PTSD, as well as publicly available GWAS results for sleep phenotypes within UK Biobank data (23 variations, encompassing four main phenotypes).MethodsGenetic correlations were estimated utilizing linkage disequilibrium score regression (LDSC), an approach that uses GWAS summary statistics to compute genetic correlations across traits, and Mendelian randomization (MR) analyses were conducted...
The risk of posttraumatic stress disorder (PTSD) following trauma is heritable, but robust common... more The risk of posttraumatic stress disorder (PTSD) following trauma is heritable, but robust common variants have yet to be identified. In a multi-ethnic cohort including over 30,000 PTSD cases and 170,000 controls we conduct a genome-wide association study of PTSD. We demonstrate SNP-based heritability estimates of 5–20%, varying by sex. Three genome-wide significant loci are identified, 2 in European and 1 in African-ancestry analyses. Analyses stratified by sex implicate 3 additional loci in men. Along with other novel genes and non-coding RNAs, a Parkinson’s disease gene involved in dopamine regulation, PARK2, is associated with PTSD. Finally, we demonstrate that polygenic risk for PTSD is significantly predictive of re-experiencing symptoms in the Million Veteran Program dataset, although specific loci did not replicate. These results demonstrate the role of genetic variation in the biology of risk for PTSD and highlight the necessity of conducting sex-stratified analyses and exp...
Bosnia and Herzegovina (BH) is located on the western part of the Balkan Peninsula. It has an are... more Bosnia and Herzegovina (BH) is located on the western part of the Balkan Peninsula. It has an area of 51 210 km2 and a population of 3 972 000. According to the Dayton Agreement of November 1995, which ended the 1992-95 war, BH comprises two ‘entities’ - the Federation of Bosnia and Herzegovina (FBH) and the Republic of Srpska (RS) - and the District of Brcko. The administrative arrangements for the management and financing of mental health services reflect this. The FBH, with 2 325 018 residents, is a federation of 10 cantons, which have equal rights and responsibilities. The RS has 1 487 785 residents and, in contrast, a centralised administration. Brcko District has just under 80 000 residents.
Post-traumatic stress disorder (PTSD) is a common and debilitating disorder. The risk of PTSD fol... more Post-traumatic stress disorder (PTSD) is a common and debilitating disorder. The risk of PTSD following trauma is heritable, but robust common variants have yet to be identified by genome-wide association studies (GWAS). We have collected a multi-ethnic cohort including over 30,000 PTSD cases and 170,000 controls. We first demonstrate significant genetic correlations across 60 PTSD cohorts to evaluate the comparability of these phenotypically heterogeneous studies. In this largest GWAS meta-analysis of PTSD to date we identify a total of 6 genome-wide significant loci, 4 in European and 2 in African-ancestry analyses. Follow-up analyses incorporated local ancestry and sex-specific effects, and functional studies. Along with other novel genes, a non-coding RNA (ncRNA) and a Parkinson’s Disease gene,PARK2, were associated with PTSD. Consistent with previous reports, SNP-based heritability estimates for PTSD range between 10-20%. Despite a significant shared liability between PTSD and ...
The international journal of neuropsychopharmacology, Jan 23, 2017
Posttraumatic Stress Disorder (PTSD) is characterized by an overactive noradrenergic system confe... more Posttraumatic Stress Disorder (PTSD) is characterized by an overactive noradrenergic system conferring core PTSD symptoms such as hyperarousal and re-experiencing. Monoamine oxidase A (MAO-A) is one of the key enzymes mediating the turnover of noradrenaline. Here, DNA methylation of the MAOA gene exonI/intronI region was investigated for the first time in regards to its role in PTSD risk and severity. MAOA methylation was analyzed via direct sequencing of sodium bisulfite treated DNA extracted from blood cells in a total sample of N=652 (m=441) patients with current PTSD, patients with remitted PTSD and healthy probands (comparison group) recruited at five centres in Bosnia-Herzegovina, Croatia, and the Republic of Kosovo. PTSD severity was measured by means of the Clinician-Administered PTSD Scale (CAPS) and its respective subscores representing distinct symptom clusters. In the male, but not the female sample, patients with current PTSD displayed hypermethylation of three CpGs (Cp...
IntroductionAlexithymia consider a cluster of cognitive and affective characteristics that includ... more IntroductionAlexithymia consider a cluster of cognitive and affective characteristics that include: inability of recognizing and describing emotions, difficulties in distinguishing feelings and physical sensations during emotional arousal, narrowed capacity for imagination and externally oriented cognitive style. Several studies links alexithymia with increased risk for physical and mental damage. Symptoms of alexithymia are documented in persons who develop PTSD in response to different types of traumatic events.ObjectivesTo examine alexithymia in war veterans.AimsTo determine whether alexithymia is significantly more present in war veterans with PTSD.MethodsCross-sectional study of 205 war veterans tested by Harvard Trauma Questionnaire and by Toronto Alexithymia Scale (TAS-20).ResultsOut of 205 war veterans 89 (43.4%) of them have alexithymia. Significantly more veterans with PTSD (78 or 75%) than without PTSD (11 or 10.9%) has alexithymia (Chi2 = 88.955, P < 0.001) was found ...
To establish the prevalence of metabolic syndrome and its parameters in group of patients with sc... more To establish the prevalence of metabolic syndrome and its parameters in group of patients with schizophrenia in polypharmacy - receiving first generation antipsychotics versus clozapine alone treated group. 48 outpatients with schizophrenia divided into two groups: the first group of 21 patients in polypharmacy with first generation antipsychotics, and the second group of 27 patients treated with clozapine alone were assessed for the presence of metabolic syndrome. We used logistic regression models to assess the relationship between metabolic syndrome and antipsychotic therapy, gender and age. Metabolic syndrome was found in 52.1% of all subjects. Compared to first generation antipsychotics polypharmacy, the monopharmacy with clozapine was associated with elevated rates of metabolic syndrome (28.6% vs. 70.4%, p=0.004). With regard to particular parameters of metabolic syndrome, the elevated plasma triglycerides were significantly more present in subjects within Clozapine group (p=0...
The aim was to analyse contacts network and satisfaction with contacts among children of parents ... more The aim was to analyse contacts network and satisfaction with contacts among children of parents with post traumatic stress disorder (PTSD). The sample consisted of 100 pupils (age 10 to 15) from two randomly chosen schools. Children were selected from general population, lived with both parents who have had war traumatic experiences. They agreed to participate in psychometric research. We divided them in two groups: observed (0) group of children (N=50) whose parents were showing symptoms of post traumatic stress disorder (PTSD) and control (C) group of children (N=50) whose parents did not show symptoms of PTSD (evaluated by Harvard trauma questionnaire-BiH version). Contact network was examined by a Map of Contact Network which includes contact and satisfaction with persons in close environment. In relation to gender representatives of fathers and mothers, sample was homogenous. The most important persons in children whose parents are showing symptoms of PTSD were schoolmates (88...
Background: To establish the prevalence of metabolic syndrome and its parameters in group of pati... more Background: To establish the prevalence of metabolic syndrome and its parameters in group of patients with schizophrenia in polypharmacy – receiving first generation antipsychotics versus clozapine alone treated group. Subjects and methods: 48 outpatients with schizophrenia divided into two groups: the first group of 21 patients in polypharmacy with first generation antipsychotics, and the second group of 27 patients treated with clozapine alone were assessed for the presence of metabolic syndrome. We used logistic regression models to assess the relationship between metabolic syndrome and antipsychotic therapy, gender and age. Results: metabolic syndrome was found in 52.1% of all subjects. Compared to first generation antipsychotics polypharmacy, the monopharmacy with clozapine was associated with elevated rates of metabolic syndrome (28.6% vs. 70.4%, p= 0.004). With regard to particular parameters of metabolic syndrome, the elevated plasma triglycerides were significantly more present in subjects within Clozapine group (p=0.03). Logistic regression analysis showed that female gender (p= 0.004), older age (p=0.56), and clozapine treatment (p= 0.005) were significantly associated with metabolic syndrome. Discussion: Results of this study are consistent with other studies, which showed that patients receiving Clozapine are at higher risk for metabolic abnormalities. Conclusion: Compared to polypharmacy with first generation antipsychotics, the higher prevalence of metabolic syndrome is found in patients treated with Clozapine alone. The most prevalent metabolic disorder is dyslipidemia. Female gender, older age, clozapine treatment are significantly associated with metabolic syndrome.
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