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Dive into the research topics where Danka Savic is active.

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Featured researches published by Danka Savic.


Psychological Medicine | 2005

Do personality traits predict post-traumatic stress ?: a prospective study in civilians experiencing air attacks

Goran Knezevic; Goran Opacic; Danka Savic; Stefan Priebe

BACKGROUND Previous studies have suggested an association between personality traits and post-traumatic stress. These studies either focused exclusively on military veterans or assessed personality traits after the traumatic event. This study investigates to what extent personality traits as assessed before the traumatic experience predict post-traumatic stress in civilians experiencing air attacks at the end of the exposure to stressful events and 1 year later. METHOD The revised version of the NEO Personality Inventory was administered to 70 students in Belgrade, Yugoslavia. In 1999, 1 or 2 years after the assessment, all students were exposed to air attacks for 11 weeks. At the end of the attacks and 1 year later post-traumatic stress was measured on the Impact of Event Scale. RESULTS Pre-trauma personality predicted 13% of the variance of intrusion scores 1 year after the attacks. There was no significant correlation between personality traits and subsequent avoidance scores at any point of time. CONCLUSIONS Personality traits that are assessed before a traumatic event can, to a limited extent, predict intrusive symptoms in a non-clinical sample of civilians. Pre-trauma assessments of personality might be less strongly associated with post-traumatic stress than personality traits obtained after the traumatic event.


Progress in Neuro-psychopharmacology & Biological Psychiatry | 2013

Lymphocyte glucocorticoid receptor expression level and hormone-binding properties differ between war trauma-exposed men with and without PTSD.

Gordana Matić; Danijela Vojnović Milutinović; Jelena Nestorov; Ivana Elaković; Sanja Manitašević Jovanović; Tatjana Perišić; Jadranka Dunđerski; Svetozar Damjanovic; Goran Knežević; Željko Špirić; Eric Vermetten; Danka Savic

OBJECTIVE Posttraumatic stress disorder (PTSD) has been shown to be associated with altered glucocorticoid receptor (GR) activity. We studied the expression and functional properties of the receptor in peripheral blood mononuclear cells (PBMCs) from non-traumatized healthy individuals (healthy controls; n=85), and war trauma-exposed individuals with current PTSD (n=113), with life-time PTSD (n=61) and without PTSD (trauma controls; n=88). The aim of the study was to distinguish the receptor alterations related to PTSD from those related to trauma itself or to resilience to PTSD. METHODS Functional status of the receptor was assessed by radioligand binding and lysozyme synthesis inhibition assays. The level of GR gene expression was measured by quantitative PCR and immunoblotting. RESULTS Current PTSD patients had the lowest, while trauma controls had the highest number of glucocorticoid binding sites (Bmax) in PBMCs. Hormone-binding potential (Bmax/KD ratio) of the receptor was diminished in the current PTSD group in comparison to all other study groups. Correlation between Bmax and KD that normally exists in healthy individuals was decreased in the current PTSD group. Contrasting Bmax data, GR protein level was lower in trauma controls than in participants with current or life-time PTSD. CONCLUSIONS Current PTSD is characterized by reduced lymphocyte GR hormone-binding potential and by disturbed compensation between Bmax and hormone-binding affinity. Resilience to PTSD is associated with enlarged fraction of the receptor molecules capable of hormone binding, within the total receptor molecule population in PBMCs.


Psychiatry Research-neuroimaging | 2013

A preliminary evaluation of leukocyte phospho-glucocorticoid receptor as a potential biomarker of depressogenic vulnerability in healthy adults

Iva Simic; Miroslav Adzic; Nadja P. Maric; Danka Savic; Jelena Djordjevic; Marina Mihaljevic; Milos Mitic; Zorana Pavlovic; Ivan Soldatovic; Marija Krstic-Demonacos; Miroslava Jasovic-Gasic; Marija B. Radojcic

The mechanism of maladaptive chronic stress response involves altered phosphorylation of the glucocorticoid receptor (GR). In this study, we investigated if important depressogenic vulnerability factors, such as neuroticism and self-reports of negative affective states, may be associated with alterations in levels of the GR and GR phosphoisoforms in peripheral blood mononuclear cells (PBMC) of healthy adults. In 21 women and 16 men we evaluated PMBC levels of total GR (tGR), GR phosphorylated at serine 211 (pGR-S211) and serine 226 (pGR-S226) and correlated these data with personality traits and current reports of stress, anxiety and depression. Also, we assessed plasma cortisol levels in all tested subjects. Our results showed that in women nuclear pGR-S226 was positively correlated with neuroticism and current reports of depression, anxiety and stress, while the ratio of nuclear pGR-S211/pGR-S226 was negatively correlated with reports of depression. None of the aforementioned correlations were significant in men. No significant relations between cortisol levels and any of GR parameters were observed. These preliminary findings highlight the value of GR phosphorylation-related research in identifying molecular biomarkers of depressogenic vulnerability, at least in women.


Psychiatry Research-neuroimaging | 2014

Mineralocorticoid receptor and heat shock protein expression levels in peripheral lymphocytes from war trauma-exposed men with and without PTSD

Gordana Matić; Danijela Vojnović Milutinović; Jelena Nestorov; Ivana Elaković; Sanja Manitašević Jovanović; Younis Mouftah Elzaedi; Tatjana Perišić; Jadranka Dunđerski; Svetozar Damjanovic; Goran Knežević; Željko Špirić; Eric Vermetten; Danka Savic

Alterations in the number and functional status of mineralocorticoid (MR) and glucocorticoid receptors (GR) may contribute to vulnerability to posttraumatic stress disorder (PTSD). Corticosteroid receptors are chaperoned by heat shock proteins Hsp90 and Hsp70. We examined relations between corticosteroid receptor and heat shock protein expression levels, and related them with war trauma exposure, PTSD and resilience to PTSD. Relative levels of MR, Hsp90 and Hsp70 were determined by immunoblotting in lymphocytes from war trauma-exposed men with current PTSD (current PTSD group, n=113), with life-time PTSD (life-time PTSD group, n=61) and without PTSD (trauma control group, n=88), and from non-traumatized healthy controls (healthy control group, n=85). Between-group differences in MR, Hsp90 and Hsp70 levels and in MR/GR ratio were not observed. The level of MR was correlated with both Hsp90 and Hsp70 levels in trauma control and healthy control groups. On the other hand, GR level was correlated only with Hsp90 level, and this correlation was evident in current PTSD and trauma control groups. In conclusion, PTSD and exposure to trauma are not related to changes in lymphocyte MR, Hsp90 or Hsp70 levels, but may be associated with disturbances in corticosteroid receptors interaction with heat shock proteins.


Psychoneuroendocrinology | 2012

Is there a biological difference between trauma-related depression and PTSD? DST says ‘NO’

Danka Savic; Goran Knezevic; Svetozar Damjanovic; Z. Spiric; Gordana Matić

The use of the low-dose dexamethasone suppression test (DST) as a potentially discriminative marker between post-traumatic stress disorder (PTSD) and depression is still under discussion. In order to compare the influence of these psychopathologies on the DST results, we examined suppression in war-traumatized subjects with one or both of these disorders, as well as in healthy controls. Based on our previous findings, we hypothesized that subjects with any disorder would exhibit higher dexamethasone suppression than healthy controls due to traumatic experiences. This study was a part of a broader project in which simultaneous psychological and biological investigations were carried out in hospital conditions on 399 male participants: 57 with PTSD, 28 with depression, 76 with PTSD+depression, and 238 healthy controls. Cortisol was measured in blood samples taken at 0900 h before and after administering 0.5mg of dexamethasone (at 2300 h). Group means ± standard deviation of cortisol suppression were: 79.4±18.5 in the PTSD group, 80.8±11.6 in the depression group, 77.5±24.6 in the group with PTSD+depression, and 66.8±34.6 in healthy controls. The first three groups suppressed significantly more than the fourth. When the number of traumas was introduced as a covariate, the differences disappeared. The hypothesis was confirmed: in respect to DST, the examined trauma-related psychopathologies showed the same pattern: hypersuppression, due to multiple traumatic experiences.


Psychobiology | 2000

A mathematical model of stress reaction: Individual differences in threshold and duration

Danka Savic; Goran Knežević; Goran Opacic

People differ in what they experience as stressful and to what extent. We define a variable—stress threshold (σ)—that links the hypothalamo-pituitary-adrenocortical (HPA) axis and the memory system in a feedback mechanism. Current σ dictates the intensity of a stimulus that turns the stress response on. On the other hand, each “jump” of the HPA axis helps long-term registration of the stressful event via concentration changes of some of its products, consequently changing the value of σ for future Stressors. After the action of a strong exterior stressor, the new stressful memory acts as an internal source of stress. We assume that its intensity decreases with the rate of processing the stressful information. This process is characterized by a time parameter τ. Both σ and τ are individual: They depend on personality traits, genetic as well as acquired. The mathematical model presented here simulates the feedback mechanism between the HPA axis and the memory system involved in stress reaction.


Journal of Affective Disorders | 2015

Posttraumatic and depressive symptoms in β-endorphin dynamics

Danka Savic; Goran Knezevic; Gordana Matić; Svetozar Damjanovic; Z. Spiric

A disturbed beta-endorphin system can be a part of the post-traumatic stress disorder (PTSD) and depression allostasis. Study subjects (N=392) included those with PTSD and/or (stress-induced) depression, and healthy controls with and without traumas. The aim of the study was to examine the network of relations centered around plasma beta-endorphin. The network included anxiety (as a personality trait), traumatic events, pain, aggressiveness, depressive symptoms, and three clusters of PTSD symptoms: intrusions, avoidance, and hyperarousal. Beta-endorphin was represented by individual mean from 13 time points (BEmean), reflecting the total amount of the peripherally secreted hormone, and the coefficient of variation (BEvar), calculated as the ratio of standard deviation to the mean, reflecting the hormone׳s dynamics. BEvar correlated with all other variables, BEmean had no correlations. Structural equation modeling (SEM) was used to examine all interrelations (including their directions) of BEvar and the state/trait variables in the context of their entirety. The model revealed that hyperarousal and anxiety were the only direct agents of peripheral beta-endorphin fluctuations, mediating the effects of other variables. Traumatic events and intrusions act on BEvar via hyperarousal, while depressive symptoms, avoidance, and pain act via anxiety. Hyperarousal should be emphasized as the main agent not only because its effect on BEvar is larger than that of anxiety, but also because it increases anxiety itself (via avoidance and pain). All influences on BEvar are positive and they indicate long-term (sensitizing) effects (as opposed to direct stimulation, for example, by acute pain, anger, etc.). Relations apart from beta-endorphin are also discussed.


Advances in Precision Medicine | 2016

A classifier driven approach to find biomarkers for affective disorders from transcription profiles in blood

W. Mazin; Joseph A. Tamm; Irina Antonijevic; Aicha Abdourahman; Munish Das; Roman Artymyshyn; Birgitte Søgaard; Mary W. Walker; Danka Savic; Gordana Matić; Svetozar Damjanovic; Ulrik Gether; Thomas Werge; Lars Vedel Kessing; Henrik Ullum; Eva Haastrup; Eric Vermetten; Paul Markovitz; Erik Mosekilde; Christophe Gerald

Gene expression profiles in blood are increasingly being used to identify biomarkers for different affective disorders. We have selected a set of 29 genes to generate expression profiles for healthy control subjects as well as for patients diagnosed with acute post-traumatic stress disorder (PTSD) and with borderline personality disorder (BPD). Measurements were performed by quantitative polymerase chain reaction (qPCR). Using the actual data in an anonym-ous form we constructed a series of artificial data sets with known gene expression profiles. These sets were used to test 14 classification algorithms and feature selection methods for their ability to identify the correct expression patterns. Application of the three most effective algorithms to the actual expression data showed that control subjects can be dis-tinguished from BPD patients based on differential expression levels of the gene transcripts Gi2, GR and MAPK14, targets that may have links to stress related diseases. Controls can also be distinguished from acute PTSD patients by differential expression levels of the transcripts for ERK2 and RGS2 that are known to be associated with mood disord-ers and social anxiety. We conclude that it is possible to identify informative transcription profiles in blood samples from individuals with affective disorders.


Psychoneuroendocrinology | 2018

PTSD and depressive symptoms are linked to DHEAS via personality

Danka Savic; Goran Knezevic; Gordana Matić; Svetozar Damjanovic

BACKGROUND Research results on dehydroepiandrosterone sulfate ester (DHEAS) in post-traumatic stress disorder (PTSD) are inconsistent. We hypothesized that personality traits could be the confounders of DHEAS levels and disease symptoms, which could in part explain the discrepancy in findings. METHOD This study was a part of a broader project in which simultaneous psychological and biological investigations were carried out in hospital conditions. 380 male subjects were categorized in four groups: A) current PTSD (n = 132), B) lifetime PTSD (n = 66), C) trauma controls (n = 101), and D) healthy controls (n = 81), matched by age. RESULTS The level of DHEAS is significantly lower in the current PTSD group than in trauma controls. All groups significantly differ in personality traits Disintegration and Neuroticism (current PTSD group having the highest scores). DHEAS is related to both PTSD and depressive symptoms; however, Structural Equation Model (SEM) shows that the relations are indirect, realized via their confounder - personality trait Disintegration. CONCLUSIONS According to our project results, DHEAS is the second putative biomarker for trauma-related disorders that fails to fulfil this expectation. It appears to be more directly related to personality than to the disease symptoms (the first one being basal cortisol). Our data promote personality as a biologically based construct with seemingly important role in understanding the mental health status.


Comprehensive Guide to Post-Traumatic Stress Disorders | 2016

Level of Expression and Functional Properties of Lymphocyte Corticosteroid Receptors as Biological Correlates of PTSD, Trauma-Exposure, or Resilience to PTSD

Gordana Matić; Danijela Vojnović Milutinović; Ivana Elaković; Jelena Nestorov; Danka Savic

Martin, Colin R. Preedy VR, Patel VB, editors. Comprehensive Guide to Post-Traumatic Stress Disorders. Springer International Publishing; 2016. p. 961–78.

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