Publications by authors named "Maja Ivkovic"

30 Publications

  • Page 1 of 1

Assessment of Cognitive Function, Social Disability and Basic Life Skills in Euthymic Patients with Bipolar Disorder.

Psychiatr Danub 2021 ;33(3):320-327

Department of Psychology, Faculty of Philosophy, University of Belgrade, Cika Ljubina 18-20, 11000, Belgrade, Serbia,

Background: Data from the literature suggests the presence of cognitive impairments which persist in the euthymic phase of bipolar disorder (BD) and have significant consequences in regards to psychosocial functioning.

The Aims Of Our Study Were: 1) to ascertain the cognitive function (CF), social disability (SD) and basic life skills (BLS) of euthymic patients diagnosed with BD, 2) their relationship and 3) to compare CF, SD and BLS in euthymic patients diagnosed with BD to euthymic patients with recurrent major depressive disorder (rMDD).

Subjects And Methods: Ninety eight euthymic patients diagnosed either with BD (N=48, mean age 48.79 years, SD = 8.587) or rMDD (N=50, mean age 50.02 years, SD = 9.826) underwent testing using the Brief Assessment of Cognition in Affective Disorders (BAC-A) test, the Sheehan Disability Scale (SDS) and the UCSD performance-based skills assessment (UPSA-brief).

Results: Euthymic patients with BD demonstrated significantly lower scores as compared to normal population values in verbal, learning and working memory, verbal fluency, attention and processing speed, affective memory for negative and positive words (p<0.01 each) and motor speed (p<0.05), but not for reasoning/problem solving (p=0.05). Furthermore, their mean total SDS score of 17.60 (SD = 6.450, Sk = -0.833) and its subscale scores were higher, while their UPSA-B total scores were lower (M = 76.01, SD = 17.148, Sk = -0.412). There was a correlation between CF, SD and BLS scores (p<0.01), as well as between BLS and SD scores (p<0.05). The analysis of variance did not however show significant differences between subgroups of patients.

Conclusion: Patients with euthymic BD had lower cognitive function, greater social disability and lower basic life skills. There were similar decreases in cognitive and psychosocial function between patients in the euthymic phase of either BD or MDD.
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http://dx.doi.org/10.24869/psyd.2021.320DOI Listing
November 2021

Assessment of Cognitive Function, Social Disability and Basic Life Skills in Euthymic Patients with Bipolar Disorder.

Psychiatr Danub 2021 ;33(3):320-327

Department of Psychology, Faculty of Philosophy, University of Belgrade, Cika Ljubina 18-20, 11000, Belgrade, Serbia,

Background: Data from the literature suggests the presence of cognitive impairments which persist in the euthymic phase of bipolar disorder (BD) and have significant consequences in regards to psychosocial functioning.

The Aims Of Our Study Were: 1) to ascertain the cognitive function (CF), social disability (SD) and basic life skills (BLS) of euthymic patients diagnosed with BD, 2) their relationship and 3) to compare CF, SD and BLS in euthymic patients diagnosed with BD to euthymic patients with recurrent major depressive disorder (rMDD).

Subjects And Methods: Ninety eight euthymic patients diagnosed either with BD (N=48, mean age 48.79 years, SD = 8.587) or rMDD (N=50, mean age 50.02 years, SD = 9.826) underwent testing using the Brief Assessment of Cognition in Affective Disorders (BAC-A) test, the Sheehan Disability Scale (SDS) and the UCSD performance-based skills assessment (UPSA-brief).

Results: Euthymic patients with BD demonstrated significantly lower scores as compared to normal population values in verbal, learning and working memory, verbal fluency, attention and processing speed, affective memory for negative and positive words (p<0.01 each) and motor speed (p<0.05), but not for reasoning/problem solving (p=0.05). Furthermore, their mean total SDS score of 17.60 (SD = 6.450, Sk = -0.833) and its subscale scores were higher, while their UPSA-B total scores were lower (M = 76.01, SD = 17.148, Sk = -0.412). There was a correlation between CF, SD and BLS scores (p<0.01), as well as between BLS and SD scores (p<0.05). The analysis of variance did not however show significant differences between subgroups of patients.

Conclusion: Patients with euthymic BD had lower cognitive function, greater social disability and lower basic life skills. There were similar decreases in cognitive and psychosocial function between patients in the euthymic phase of either BD or MDD.
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http://dx.doi.org/10.24869/psyd.2021.320DOI Listing
November 2021

Internet use during coronavirus disease of 2019 pandemic: Psychiatric history and sociodemographics as predictors.

Indian J Psychiatry 2020 Sep 28;62(Suppl 3):S383-S390. Epub 2020 Sep 28.

Department for Affective Disorders, Clinic of Psychiatry, Clinical Center of Serbia, Belgrade, Serbia.

Coronavirus disease of 2019 (COVID-19) pandemic and related containment measures have grossly affected the daily living and created a need for alternative ways of social communication and entertainment. The aim of this study was to explore the use of various Internet contents depending on sociodemographics and on psychiatric history of participants. This cross-sectional, population-based study is a part of a wider international multicenter study. A total of 1275 participants across Serbia (71.1% of females; average age = 41.81 ± 12.52 years) were recruited using two-level chain-referral sampling method. The participants filled in an anonymous online questionnaire that included questions on sociodemographic data, psychiatric history, and various aspects of increased Internet use since the pandemic. The data were analyzed using a series of multiple logistic regressions. About two-thirds of the sample reported using Internet more during the pandemic. All of the tested regression models, apart from models predicting browsing religion and travel/tourism, were significant, explaining from about 2% (for the contents specific for COVID-19) up to 34.4% (for the sexual content) of variance of use. Reporting a previously diagnosed psychiatric disorder was a significant predictor of greater Instagram use and browsing sexual and sport-related content since the pandemic. To the best of our knowledge, the study is the first to report on the relationship between Internet using and mental health, during COVID-19 pandemic, in the Balkan region. The findings showed various patterns of the increased use of Internet contents since the pandemic referring to both potentially positive and negative Internet influences.
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http://dx.doi.org/10.4103/psychiatry.IndianJPsychiatry_1036_20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7659784PMC
September 2020

Internet use during coronavirus disease of 2019 pandemic: Psychiatric history and sociodemographics as predictors.

Indian J Psychiatry 2020 Sep 28;62(Suppl 3):S383-S390. Epub 2020 Sep 28.

Department for Affective Disorders, Clinic of Psychiatry, Clinical Center of Serbia, Belgrade, Serbia.

Coronavirus disease of 2019 (COVID-19) pandemic and related containment measures have grossly affected the daily living and created a need for alternative ways of social communication and entertainment. The aim of this study was to explore the use of various Internet contents depending on sociodemographics and on psychiatric history of participants. This cross-sectional, population-based study is a part of a wider international multicenter study. A total of 1275 participants across Serbia (71.1% of females; average age = 41.81 ± 12.52 years) were recruited using two-level chain-referral sampling method. The participants filled in an anonymous online questionnaire that included questions on sociodemographic data, psychiatric history, and various aspects of increased Internet use since the pandemic. The data were analyzed using a series of multiple logistic regressions. About two-thirds of the sample reported using Internet more during the pandemic. All of the tested regression models, apart from models predicting browsing religion and travel/tourism, were significant, explaining from about 2% (for the contents specific for COVID-19) up to 34.4% (for the sexual content) of variance of use. Reporting a previously diagnosed psychiatric disorder was a significant predictor of greater Instagram use and browsing sexual and sport-related content since the pandemic. To the best of our knowledge, the study is the first to report on the relationship between Internet using and mental health, during COVID-19 pandemic, in the Balkan region. The findings showed various patterns of the increased use of Internet contents since the pandemic referring to both potentially positive and negative Internet influences.
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http://dx.doi.org/10.4103/psychiatry.IndianJPsychiatry_1036_20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7659784PMC
September 2020

sVCAM-1, sICAM-1, TNF-α and IL-6 levels in bipolar disorder type I: Acute, longitudinal and therapeutic implications.

World J Biol Psychiatry 2018 14;19(sup2):S41-S51. Epub 2016 Dec 14.

a Clinic of Psychiatry , Clinical Centre of Serbia , Belgrade , Serbia.

Objectives: To explore the serum levels of soluble vascular cell adhesion molecule-1 (sVCAM-1), soluble intercellular cell adhesion molecule-1 (sICAM-1), tumour necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in patients with bipolar disorder (BD), with regard to acute episode characteristics, course of the disorder and treatment.

Methods: The study group consisted of 83 patients diagnosed with BD type I. The control group consisted of 73 healthy individuals, matched with the study group according to age, gender and body mass index. The serum levels of sVCAM-1, sICAM-1, TNF-α and IL-6 were measured by ELISA.

Results: Compared with healthy controls, significantly elevated levels of IL-6 and sICAM-1 and significantly lower levels of TNF-α and sVCAM-1 were identified in acute and remission phases of BD. The acute serum levels of sVCAM-1 were associated with the type and severity of acute mood symptoms as well as with course of illness characteristics. TNF-α was associated with duration of untreated disorder and type of treatment.

Conclusions: BD is related to both acute and long-term alterations of immune mediators, including adhesion molecules. The potential immunomodulatory role of pharmacotherapeutic treatment is also to be considered in BD.
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http://dx.doi.org/10.1080/15622975.2016.1259498DOI Listing
June 2019

Predictive value of sICAM-1 and sVCAM-1 as biomarkers of affective temperaments in healthy young adults.

J Affect Disord 2017 Jan 22;207:47-52. Epub 2016 Sep 22.

Clinic of Psychiatry, Clinical Centre of Serbia, Pasterova 2, 11000 Belgrade, Serbia; School of Medicine, University of Belgrade, Dr Subotica 8, 11000 Belgrade, Serbia.

Background: Affective temperaments are intermediate phenotypes for major affective disorders and are reported to have a neuroimmune etiopathogenesis. Here we investigated the role of soluble intercellular cell adhesion molecule-1 (sICAM-1) and soluble vascular cell adhesion molecule-1 (sVCAM-1) in affective temperaments and mood symptoms in healthy adults.

Methods: Healthy adults (n=94) were screened for psychiatric disorders using the nonpatient version of the Structured Clinical Interview for DSM-IV-I and II. Subjects with medical conditions associated with changes in inflammatory response were excluded, deriving the final sample (n=68). Affective temperaments were evaluated with Temperament Evaluation of Memphis, Pisa, Paris and San Diego-Autoquestionnaire (TEMPS-A). State mood symptoms were assessed using the Young Mania Rating Scale and Montgomery-Åsberg Depression Rating Scale. Serum sICAM-1 and sVCAM-1 levels were measured using enzyme-linked immunosorbent assay.

Results: After adjusting for confounders (age, gender, BMI, and smoking habits), a high negative correlation between depressive and irritable temperament TEMPS-A scores and sVCAM-1 levels was detected. Although we identified no association between sICAM-1 levels and affective temperament scores, sICAM-1 was related to the state severity of manic symptoms. In a multiple linear regression model, sVCAM-1 remained a significant predictor of depressive but not irritable temperament scores.

Limitations: The temperaments were estimated on the basis of self-report questionnaire.

Conclusions: Our findings suggest that sVCAM-1 is related to affective temperaments, and it is a trait marker for liability to mood disorders. This relationship between alterations in cellular adhesion and affective temperament may be important for vulnerability to affective disorders.
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http://dx.doi.org/10.1016/j.jad.2016.09.017DOI Listing
January 2017

Predictive value of sICAM-1 and sVCAM-1 as biomarkers of affective temperaments in healthy young adults.

J Affect Disord 2017 Jan 22;207:47-52. Epub 2016 Sep 22.

Clinic of Psychiatry, Clinical Centre of Serbia, Pasterova 2, 11000 Belgrade, Serbia; School of Medicine, University of Belgrade, Dr Subotica 8, 11000 Belgrade, Serbia.

Background: Affective temperaments are intermediate phenotypes for major affective disorders and are reported to have a neuroimmune etiopathogenesis. Here we investigated the role of soluble intercellular cell adhesion molecule-1 (sICAM-1) and soluble vascular cell adhesion molecule-1 (sVCAM-1) in affective temperaments and mood symptoms in healthy adults.

Methods: Healthy adults (n=94) were screened for psychiatric disorders using the nonpatient version of the Structured Clinical Interview for DSM-IV-I and II. Subjects with medical conditions associated with changes in inflammatory response were excluded, deriving the final sample (n=68). Affective temperaments were evaluated with Temperament Evaluation of Memphis, Pisa, Paris and San Diego-Autoquestionnaire (TEMPS-A). State mood symptoms were assessed using the Young Mania Rating Scale and Montgomery-Åsberg Depression Rating Scale. Serum sICAM-1 and sVCAM-1 levels were measured using enzyme-linked immunosorbent assay.

Results: After adjusting for confounders (age, gender, BMI, and smoking habits), a high negative correlation between depressive and irritable temperament TEMPS-A scores and sVCAM-1 levels was detected. Although we identified no association between sICAM-1 levels and affective temperament scores, sICAM-1 was related to the state severity of manic symptoms. In a multiple linear regression model, sVCAM-1 remained a significant predictor of depressive but not irritable temperament scores.

Limitations: The temperaments were estimated on the basis of self-report questionnaire.

Conclusions: Our findings suggest that sVCAM-1 is related to affective temperaments, and it is a trait marker for liability to mood disorders. This relationship between alterations in cellular adhesion and affective temperament may be important for vulnerability to affective disorders.
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http://dx.doi.org/10.1016/j.jad.2016.09.017DOI Listing
January 2017

Predictive value of sICAM-1 and sVCAM-1 as biomarkers of affective temperaments in healthy young adults.

J Affect Disord 2017 Jan 22;207:47-52. Epub 2016 Sep 22.

Clinic of Psychiatry, Clinical Centre of Serbia, Pasterova 2, 11000 Belgrade, Serbia; School of Medicine, University of Belgrade, Dr Subotica 8, 11000 Belgrade, Serbia.

Background: Affective temperaments are intermediate phenotypes for major affective disorders and are reported to have a neuroimmune etiopathogenesis. Here we investigated the role of soluble intercellular cell adhesion molecule-1 (sICAM-1) and soluble vascular cell adhesion molecule-1 (sVCAM-1) in affective temperaments and mood symptoms in healthy adults.

Methods: Healthy adults (n=94) were screened for psychiatric disorders using the nonpatient version of the Structured Clinical Interview for DSM-IV-I and II. Subjects with medical conditions associated with changes in inflammatory response were excluded, deriving the final sample (n=68). Affective temperaments were evaluated with Temperament Evaluation of Memphis, Pisa, Paris and San Diego-Autoquestionnaire (TEMPS-A). State mood symptoms were assessed using the Young Mania Rating Scale and Montgomery-Åsberg Depression Rating Scale. Serum sICAM-1 and sVCAM-1 levels were measured using enzyme-linked immunosorbent assay.

Results: After adjusting for confounders (age, gender, BMI, and smoking habits), a high negative correlation between depressive and irritable temperament TEMPS-A scores and sVCAM-1 levels was detected. Although we identified no association between sICAM-1 levels and affective temperament scores, sICAM-1 was related to the state severity of manic symptoms. In a multiple linear regression model, sVCAM-1 remained a significant predictor of depressive but not irritable temperament scores.

Limitations: The temperaments were estimated on the basis of self-report questionnaire.

Conclusions: Our findings suggest that sVCAM-1 is related to affective temperaments, and it is a trait marker for liability to mood disorders. This relationship between alterations in cellular adhesion and affective temperament may be important for vulnerability to affective disorders.
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http://dx.doi.org/10.1016/j.jad.2016.09.017DOI Listing
January 2017

MiR-155 expression level changes might be associated with initial phases of breast cancer pathogenesis and lymph-node metastasis.

Cancer Biomark 2016 ;16(3):385-94

University of Belgrade-Vinča Institute of Nuclear Sciences, Mike Petrovića Alasa, Belgrade, Serbia.

Background: Breast carcinoma is heterogeneous disease. Understanding the process of invasion and metastasis and the selection of the therapy for patients with breast carcinomas still remains difficult. MicroRNAs are powerful gene expression regulators. Because of inconsistent findings, we have analyzed potential difference in miR-155 levels in three breast cancer groups.

Objectives: Our goals were to examine miR-155 expression levels in normal tissue, non-invasive and invasive breast carcinomas, and their association with standard clinical and pathological parameters and oncomiR-21, and to investigate the ability of miR-155 to separate invasive breast carcinomas with non-invasive component from pure invasive.

Methods: In the group of 40 breast tissue samples, relative expression levels of miR-155 were examined with stem-loop quantitative real-time PCR using TaqMan technology.

Results: The significant difference among four examined groups of the breast tissue was detected (p = 0.001). In the group of pure invasive tumors, patients with positive nodal status had significantly higher miR-155 levels (p = 0.046).

Conclusion: Our results suggest that miR-155 might be involved in breast cancer pathogenesis and in tumor spreading to the lymph nodes, and that it might be used as biomarker for additional stratification of patients with invasive breast carcinomas with non-invasive component.
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http://dx.doi.org/10.3233/CBM-160577DOI Listing
December 2016

Role of sICAM-1 and sVCAM-1 as biomarkers in early and late stages of schizophrenia.

J Psychiatr Res 2016 Feb 6;73:45-52. Epub 2015 Nov 6.

Clinic of Psychiatry, Clinical Centre of Serbia, Pasterova 2, 11000, Belgrade, Serbia; School of Medicine, University of Belgrade, Dr Subotica 8, 11000, Belgrade, Serbia.

Schizophrenia (SZ) is a neuroprogressive disorder presenting with biochemical, functional, and structural changes, which differ from early to late stages of the illness. We explored the differences in serum levels of soluble intercellular cell adhesion molecule-1 (sICAM-1) and soluble vascular cell adhesion molecule-1 (sVCAM-1) between early and late stages of SZ, in regard to clinical characteristics and treatment application. Serum levels of sICAM-1 and sVCAM-1 were measured in 80 patients with SZ (40 early stage; 40 late stage), and compared with 80 healthy controls, matched by age, gender, body mass index, and smoking habits with each SZ group. Serum levels of sICAM-1 and sVCAM-1 were measured using ELISA. The severity of psychopathology was assessed using the Clinical Global Impression Scale and five-factor Positive and Negative Symptoms in Schizophrenia Scale. After adjustment for confounders, we noticed normal levels of sICAM-1 in the early stage, and elevated levels of sICAM-1 in the late stage of SZ. sVCAM-1 levels were decreased in both stages of SZ. Higher sICAM-1 levels have been related to more pronounced cognitive deficit and excitement symptoms in the early stage of SZ and to favorable characteristics of treatment application in both stages. SZ is associated with changes in the levels of adhesion molecules that vary from early to late stages of the illness. This implies that the concept of biochemical staging is applicable in SZ, at least for markers of cellular adhesion.
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http://dx.doi.org/10.1016/j.jpsychires.2015.11.002DOI Listing
February 2016

Cannabis and psychosis revisited.

Psychiatr Danub 2015 Mar;27(1):97-100

School of Medicine, Clinic for Psychiatry, Clinical Center of Serbia, University of Belgrade, Pasterova 2, 11000 Belgrade, Serbia.

The association between cannabinoids and psychosis has been known for almost a thousand years, but it is still speculated whether cannabis use may be a contributory cause of psychosis, that is, whether it may precipitate schizophrenia in those at risk. In this paper, we will briefly present the data from individual longitudinal studies in the field, together with the factors that are considered important for the association of cannabis abuse and occurrence of schizophrenia and prevention opportunities in the target population. The reviewed studies clearly suggest that cannabis abuse predicts an increased risk for schizophrenia, particularly in young adults. They underline both the need to create adequate prevention measures and consequently avoid the occurrence of the disease in the young at risk. Particular attention should be additionally devoted toward encouraging the young presenting with psychotic symptoms to stop or, at the very least, reduce the frequency of cannabis abuse. The issues are undoubtedly to be addressed by the health care system in general.
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March 2015

Cannabis and psychosis revisited.

Psychiatr Danub 2015 Mar;27(1):97-100

School of Medicine, Clinic for Psychiatry, Clinical Center of Serbia, University of Belgrade, Pasterova 2, 11000 Belgrade, Serbia.

The association between cannabinoids and psychosis has been known for almost a thousand years, but it is still speculated whether cannabis use may be a contributory cause of psychosis, that is, whether it may precipitate schizophrenia in those at risk. In this paper, we will briefly present the data from individual longitudinal studies in the field, together with the factors that are considered important for the association of cannabis abuse and occurrence of schizophrenia and prevention opportunities in the target population. The reviewed studies clearly suggest that cannabis abuse predicts an increased risk for schizophrenia, particularly in young adults. They underline both the need to create adequate prevention measures and consequently avoid the occurrence of the disease in the young at risk. Particular attention should be additionally devoted toward encouraging the young presenting with psychotic symptoms to stop or, at the very least, reduce the frequency of cannabis abuse. The issues are undoubtedly to be addressed by the health care system in general.
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March 2015

Serum levels of interleukin-6 and tumor necrosis factor-alpha in exacerbation and remission phase of schizophrenia.

Psychiatr Danub 2013 Mar;25(1):55-61

Clinic for Psychiatry, Clinical Centre of Serbia, Belgrade, Serbia.

Background: The variations in proinflamatory cytokine levels have been associated with schizophrenia (SCH), duration of illness, psychopathology and treatment. The aim of the study was to investigate serum levels of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) in schizophrenic patients during exacerbation and remission, and its association with course of illness and therapy.

Subjects And Methods: We measured serum levels of IL-6 and TNF-α in 43 schizophrenic patients in exacerbation and remission and compared them to 29 healthy controls, matched by sex, age, body mass index (BMI) and smoking habits. The severity of psychopathology was assessed using the Positive and Negative Syndrome Scale (PANSS).

Results: There was no difference in levels of IL-6 and TNF-α in exacerbation compared to remission in schizophrenic patients. IL-6 was higher and TNF-α was lower in schizophrenic patients in both exacerbation and remission in comparison with healthy controls. TNF-α in exacerbation was in negative correlation with IL-6 in remission. No statistical significance was found between levels of cytokines and sex, age, BMI, smoking habits, antipsychotic medication, duration of treatment and duration of illness. IL-6 levels were in positive correlation with the age of onset and the duration of untreated psychosis. In schizophrenic patients on adjunctive treatment with mood stabilizers, TNF-α levels increased in remission.

Conclusion: Our results suggest that the connection between schizophrenia, cytokines and medication is multifaceted, and not necessarily linear. Adjunct mood stabilizers not only ameliorate psychopathology, but might convey immunomodulatory effects as well. Further longitudinal studies could elucidate potential beneficial effect of combined therapy in treatment of SCH.
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March 2013

Melancholic and atypical major depression--connection between cytokines, psychopathology and treatment.

Prog Neuropsychopharmacol Biol Psychiatry 2013 Jun 28;43:1-6. Epub 2012 Nov 28.

Clinic of Psychiatry, Clinical Centre of Serbia, Pasterova 2, 11000 Belgrade, Serbia.

Background And Purpose: Growing scientific evidence indicates that there is a correlation between depression and alternations in the immune system. The main aim of the study was to investigate serum levels of Interleukin-6 (IL-6) and Tumour Necrosis Factor-alpha (TNF-α) in melancholic and atypical depressive patients during acute exacerbations of illness, compared to healthy subjects. The secondary aim was to explore a possible association between cytokine levels and clinical characteristics, as well as total duration of prior antidepressant treatment.

Method: We measured serum levels of IL-6 and TNF-α in 47 patients suffering from major depressive disorder (MDD) (29 melancholic and 18 atypical) in exacerbation of illness, compared to 39 healthy controls, matched by sex, body mass index (BMI) and smoking habits. Serum levels of IL-6 and TNF-α were measured by enzyme-linked immunosorbent assay (ELISA). The severity of psychopathology was assessed using the Hamilton Depression Rating Scale (HDRS).

Results: IL-6 was significantly elevated in melancholic depressive patients (MDD-M) compared to healthy controls, while no difference was found between the patients with atypical depression (MDD-A) and the healthy group. Lower TNF-α serum level was found both in melancholic and in patients with atypical depression, compared with healthy subjects. We detected a positive correlation between cytokine levels in atypical, but not in melancholic subjects. Sex, age, smoking habits and BMI were not associated to cytokine levels in neither group. Clinical parameters (duration of illness, current episode, age of onset) were related to cytokine levels in atypical depression, while the duration of lifetime exposure to antidepressant treatment correlated to IL-6 serum levels in both melancholic and atypical depression.

Conclusion: Our results suggest that the difference in pro-inflammatory cytokine levels could reflect a biological difference between melancholic and atypical depression. A positive correlation between the cytokines (TNF-α and IL-6) observed in depressive patients with atypical features, might be influenced by chronic course of illness, while IL-6 elevation could represent a state indicator for acute exacerbation, especially in melancholic patients. Total duration of antidepressant treatment could be a relevant factor influencing the immune status of patients who suffer either from melancholic or atypical depression.
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http://dx.doi.org/10.1016/j.pnpbp.2012.11.009DOI Listing
June 2013

Knowledge: a possible tool in shaping medical professionals' attitudes towards homosexuality.

Psychiatr Danub 2012 Jun;24(2):143-51

Clinic for Psychiatry, Clinical Centre of Serbia, Belgrade, Pasterova 2, 11000 Belgrade, Serbia.

Background: The attitudes of medical professionals towards homosexuals can influence their willingness to provide these individuals with medical help. The study evaluated the medical professionals' knowledge about homosexuality and their attitudes towards it.

Subjects And Methods: The sample consisted of 177 participants (physicians n=79 and students n=98). The study respondents anonymously completed three questionnaires (socio-demographic questionnaire, the questionnaire on knowledge, and the questionnaire on attitudes towards homosexuals).

Results: Male and religious participants showed a lower level of knowledge and a greater tendency to stigmatize. Furthermore, the subjects who knew more about homosexuality tended to hold less stigmatizing attitude. Age group, specialty (psychiatry, gynecology, internal medicine and surgery), and student's/physician's status had no effect on stigmatization. The study showed that the final year students/ residents had more knowledge than the second year students/specialists did. Knowledge had significant negative predictive effect on attitudes in the analyzed predictive model.

Conclusions: To our knowledge, this has been the first study in Serbia and Eastern Europe, which provides information on knowledge and attitudes of health professionals towards homosexuality. We would like to point out the degree of knowledge on homosexuality as a possible, but not exclusive tool in shaping the attitudes towards homosexuals and reducing stigmatization. However, regardless of the personal attitude, knowledge and variable acceptance of the homosexuals' rights, medical professionals' main task is to resist discriminative behavior and provide professional medical help to both homosexual and heterosexual patients.
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June 2012

The framework of family therapy in clinical practice and research in Serbia.

Int Rev Psychiatry 2012 Apr;24(2):86-90

Department of Affective Disorders, Clinic of Psychiatry, Clinical Centre of Serbia, Belgrade, Serbia.

In the last two decades, Serbia has had to deal with multiple social and economic problems reflecting on society's demographics and seemed to weaken its core cell - the family. The paper describes the framework of family therapy in clinical practice and research, within the recent transition of the Serbian family. Family therapy treatment in Serbia uses the systemic family therapy (SFT) approach, applied according to the standards of the European Association for Psychotherapy. A large number of professionals who practise in Serbia hold European qualifications, setting high standards in education, clinical practice, and research. Although SFT is also available in the private sector, the majority of patients are still treated in state institutions. Family therapy is often used for adults and adolescents with psychosis and addictions in psychiatric hospital settings. However, in counselling centres it is used for marital and relationship problems. Interestingly, family therapy has recently started to emerge as a more frequent tool in consultation-liaison, particularly psycho-oncology but also in correctional institutions. The clinical practice and research interests are interlinked with changes in social settings.
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http://dx.doi.org/10.3109/09540261.2012.657161DOI Listing
April 2012

Posttraumatic stress disorder in a World War II concentration camp survivor caused by the attack of two German shepherd dogs: case report and review of the literature.

Forensic Sci Int 2011 May 9;208(1-3):e15-9. Epub 2011 Mar 9.

School of Medicine, University of Belgrade, Belgrade, Serbia.

A 79-year-old woman suffered from acute posttraumatic stress disorder (PTSD) and a loco typico, non-displaced fracture of her right distal radius due to an incident involving the assault of two unleashed owned dogs, which suddenly ran into her and aggressively jumped on her chest and knocked her down to the ground. Recovery for her damage claim concerning pain and disability due to her right forearm fracture caused by the incident, was not the issue in the litigation concerned. However, the issue of delayed impact of her previous Holocaust experience placed a significant challenge on M.N., as a plaintiff, in establishing a causal link between the posttraumatic stress disorder concerned and the alleged harmful action of the defendants, the owners of the two dogs. The case reported here proved interesting and instructive not only in the sense of addressing main issues relevant to litigation for psychological damage related to reactivated PTSD and delayed PTSD, but also in the sense of pointing at the clinical relevance of dog assaults on humans which, even without dog bite injuries, may result in a severe traumatization and eventual civil lawsuit.
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http://dx.doi.org/10.1016/j.forsciint.2011.02.016DOI Listing
May 2011

Schizophrenia and apolipoprotein E gene polymorphism in Serbian population.

Int J Neurosci 2010 Jul;120(7):502-6

Faculty of Biology, University of Belgrade, Belgrade, Serbia.

Apolipoprotein E (APOE) gene variants are associated with alterations in brain function and increased risk of Alzheimer's disease (AD) and conflicting results have been reported in schizophrenia. Our results showed no significant differences in APOE allele or genotype frequencies between the Serbian schizophrenic patients and control individuals. However, we observed a possible association between particular subtypes of schizophrenia and APOE epsilon3/epsilon3 genotype (p = .01221) and epsilon4 allele showed a tendency toward positive association with responding to typical neuroleptics. APOE genotypes have no major influence on risk of schizophrenia, treatment and response to conventional antipsychotics, and age of onset in schizophrenia.
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http://dx.doi.org/10.3109/00207451003765956DOI Listing
July 2010

Lamotrigine versus lithium augmentation of antidepressant therapy in treatment-resistant depression: efficacy and tolerability.

Psychiatr Danub 2009 Jun;21(2):187-93

Institute for psychiatry, Clinical Center of Serbia, Pasterova 2, 11000 Belgrade, Serbia.

Background: Mood stabilizer augmentation of standard antidepressant drugs has been shown to be effective in treatment-resistant depression. Despite the reported high overall efficacy, lithium has been relatively underused in recent years. Lamotrigine, a novel anticonvulsant recently recognized as a mood stabilizer, seems to have putative antidepressive properties. The aim of the study was to investigate lamotrigine efficacy and tolerability as antidepressant augmentation for unipolar treatment-resistant depression compared to lithium.

Subjects And Methods: 88 patients suffering from treatment-resistant Major depressive disorder, having acute recurrent depressive episodes according to DSM-IV criteria, were enrolled in the study. This was an open-label trial with a flexible dosing regimen. All patients, received antidepressants in full therapeutic doses. They were divided into two augmentation groups: 46 patients received 50-200 mg/day lamotrigine, and 42 patients received 600-1200 mg/day lithium. The Hamilton Rating Scale for Depression (HAM-D) and The Clinical Global Impression scale (CGI) were used to monitor therapeutic efficacy. Patients were evaluated weekly for an 8 week treatment period.

Results: The HAM-D total score was significantly reduced in both treatment groups at the study endpoint, without any difference between the groups. However, significant clinical improvement was reached within the second treatment week in the lamotrigine group compared to the lithium group (p=0.01 vs. lithium). Lamotrigine showed significant efficacy on the HAM-D item 1(depressed mood; p=0.01), item 7 (work and interest; p=0.01) and CGI-Improvement scale (p=0.02). The drop-out rate due to treatment failure was lower in the lamotrigine group (n=1) compared to the lithium (n=4) group. Also, the incidence of side effects did not differ between the groups.

Conclusions: Our results suggest that lamotrigine could be useful as augmentation of antidepressants for treatment-resistant unipolar depression. Also, lamotrigine may accelerate the onset of antidepressant action, and therefore might be useful in treatment of major depression in general.
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June 2009

Comparative analysis of soft neurological signs in positive and negative subtype of schizophrenia.

Psychiatr Danub 2009 Jun;21(2):174-8

Institute of Psychiatry Clinical Center of Serbia, Pasterova 2, 11000 Belgrade, Serbia.

Background: The objective of the study was to investigate neurological deficit in schizophrenia and to compare soft neurological signs in positive and negative subtypes of schizophrenia.

Subjects And Methods: 66 patients with schizophrenia were evaluated with the Positive and Negative Syndrome Scale to classify the subtype of schizophrenia: positive subtype (36 patients) and negative subtype (30 patients), all of which were entering into remission. To examine the neurological soft signs we compared scores on the Neurological Evaluation Scale (NES) for positive and negative subtype.

Results: The negative subtype of schizophrenia showed significantly higher neurological soft signs in comparison to the positive subtype, with reduced functioning in the sensory integration and motor coordination subscale as well as the other subscale.

Conclusion: The main finding in this study indicates that patients with schizophrenia have neurological impairment, and that the negative subtype has significantly higher neurological impairment than the positive subtype. The results further support the significance of the soft neurological signs as a possible marker of different subtypes of schizophrenia.
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June 2009

Predicting violence in veterans with posttraumatic stress disorder.

Vojnosanit Pregl 2009 Jan;66(1):13-21

Clinical Centre of Serbia, Institute of Psychiatry, Belgrade, Serbia.

Background/aim: Frequent expression of negative affects, hostility and violent behavior in individuals suffering from posttraumatic stress disorder (PTSD) were recognized long ago, and have been retrospectively well documented in war veterans with PTSD who were shown to have an elevated risk for violent behavior when compared to both veterans without PTSD and other psychiatric patients. The aim of this study was to evaluate the accuracy of clinical prediction of violence in combat veterans suffering from PTSD.

Methods: The subjects of this study, 104 male combat veterans with PTSD were assessed with the Historical, Clinical and Risk Management 20 (HCR-20), a 20-item clinician-rated instrument for assessing the risks for violence, and their acts of violence during one-year follow-up period were registered based on bimonthly check-up interviews.

Results: Our findings showed that the HCR-20, as an actuarial measure, had good internal consistency reliability (alpha=0.82), excellent interrater reliability (Interaclass Correlation ICC=0.85), as well as excellent predictive validity for acts of any violence, non-physical violence or physical violence in the follow-up period (AUC = 0.82-0.86). The HCR-20 also had good interrater reliability (Cohen's kappa = 0.74), and acceptable predictive accuracy for each outcome criterion (AUC = 0.73-0.79).

Conclusion: The results of this research confirm that the HCR-20 may also be applied in prediction of violent behavior in the population of patients suffering from PTSD with reliability and validity comparable with the results of previous studies where this instrument was administered to other populations of psychiatric patients.
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http://dx.doi.org/10.2298/vsp0901013jDOI Listing
January 2009

Reliability and validity of DSM-IV Axis V scales in a clinical sample of veterans with posttraumatic stress disorder.

Psychiatr Danub 2008 Sep;20(3):286-300

Institute of Psychiatry, Clinical Centre of Serbia, Belgrade, Serbia.

Objectives: Psychometric properties of the DSM-IV Axis V scales in measuring adaptational functioning of psychotraumatised veterans have been chosen as the focus of this study.

Subjects And Methods: The reliability and validity of the Global Assessment of Functioning Scale (GAF), the Social and Occupational Assessment Scale (SOFAS), and the Global Assessment of Relational Functioning (GARF) were examined in a clinical sample of 129 veterans with posttraumatic stress disorder (PTSD).

Results: The interrater reliability of the GAF (ICC=0.82) and the SOFAS (ICC=0.83) was excellent, while the interrater reliability of the GARF (ICC=0.75) was good. Correlations with other clinician-rated scales of psychopathology and overall functioning showed that the GAF is primarily related to a reduction in functioning due to psychiatric symptoms, while an assessment of functioning beyond psychopathology, considering the effects of the individual's general medical condition as well, was provided by the SOFAS and the GARF, which is of importance for a comprehensive evaluation of the patients' health status. The factor analysis of the Axis V scales revealed a theoretically meaningful, single common factor (variance accounted for by the extracted factor = 76.91%), while observed differences, between the subjects with complete and partial PTSD, in scores on the axis V scales support further use of the axis V scales as useful outcome variables.

Conclusion: The issue of a valid and reliable measurement of functional impairment is of paramount importance not only in the domain of clinical psychiatry but in forensic practice as well. In this respect, our findings give strong support to extending the scope of the DSM axis V scales with the two experimental scales which provide both conceptual framework and useful tools for reliable and valid evaluation of adaptatinal functioning in persons suffering from PTSD.
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September 2008

Plasma homocysteine levels in young male patients in the exacerbation and remission phase of schizophrenia.

Prog Neuropsychopharmacol Biol Psychiatry 2008 Dec 15;32(8):1921-6. Epub 2008 Sep 15.

Institute of Medical and Clinical Biochemistry, School of Medicine, Pasterova 2, 11000 Belgrade, Serbia.

High levels of homocysteine (Hcy) were suggested to contribute to the pathogenesis of schizophrenia. Recent investigations have shown that treatment with folic acid, vitamin B-12 and pyridoxine are effective in reducing Hcy levels while concomitantly reducing the score of positive and negative symptoms in schizophrenic patients. In addition to the availability of nutrients (mainly folate, vitamins B6 and B12), plasma Hcy concentrations are dependent on complex metabolic regulation that could be disrupted in schizophrenia. This study was designed to test the influence of disease activity on plasma Hcy levels. Plasma Hcy concentrations were measured in male chronic schizophrenic patients with a predominantly positive (SCH (+)) or predominantly negative (SCH (-)) syndrome in schizophrenia immediately upon admission to the hospital (exacerbation phase) and one month later (remission phase). During this period patients received antipsychotic medications without vitamin therapy. The effects of age, duration of illness, folate and B12 concentrations, as well as smoking and coffee consumption habits on the observed changes were evaluated. Age- and sex-matched subjects were included in the control group. In the control group plasma Hcy concentration was 8.75+/-1.84 micromol/L. In the exacerbation phase plasma Hcy concentrations were significantly increased both in SCH (+) (14.91+/-6.19 micromol/L) and SCH (-) groups (12.8+/-3.27 micromol/L). There was no difference in plasma Hcy concentrations between SCH (+) and SCH (-) patients. Serum folate and B12 concentrations were not significantly different in any of the investigated groups of subjects. The plasma Hcy concentrations could not be correlated with age, duration of illness, the score of positive symptoms or the concentration of folate and vitamin B12. A positive correlation was found between plasma Hcy level and score of negative symptoms in both groups of patients. No correlation was found between smoking or coffee consumption habits and plasma Hcy concentrations. All patients exhibited decreased plasma Hcy levels in the remission phase of the illness, with a mean decrease of 2.68+/-1.57 micromol/L. Folate and B12 levels did not differ in the exacerbation and remission phases of the illness. The significant decrease of plasma Hcy levels, without changes in folate and vitamin B12 concentrations in the remission phase of schizophrenia, could indicate an influence of a pathogenetic process involved in schizophrenia on Hcy metabolism.
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http://dx.doi.org/10.1016/j.pnpbp.2008.09.009DOI Listing
December 2008

Low bone mineral density and high bone metabolism turnover in premenopausal women with unipolar depression.

Bone 2008 Mar 4;42(3):582-90. Epub 2007 Dec 4.

Clinic of Rheumatology, Military Medical Academy, Crnotravska 17, Belgrade, Serbia.

Introduction And Hypothesis: The majority of studies reporting decreased bone mineral density (BMD) in patients with unipolar depression neglected sex and age differences and menopause as the most important risk factor for osteoporosis. We presumed that physically healthy premenopausal women with unipolar depression have decreased BMD and altered bone cell metabolism.

Methods: BMD at lumbar spine and femoral neck by dual X-ray absorptiometry, bone alkaline phosphatase sera activity, 5b-tartarate resistant acid phosphatase sera activity and urine N-terminal telopeptide were measured in 73 premenopausal women with unipolar depression and compared with 47 healthy, age- and osteoporosis risk factors-matched premenopausal women. The duration and severity of depression, hormonal status (cortisol, prolactin, parathormone, oestradiol), antidepressive treatment, and physical activity through whole and modified QUALEFFO-41 questionnaire were evaluated. The results were statistically elaborated by the chi-square test, Student's t-test for independent samples, one-way analysis of variance - ANOVA, one-sample Kolmogorov-Smirnov test. Correlations were assessed by means of Pearson's coefficient.

Results: Patients with unipolar depression had significantly lower BMD, the decrease of which correlated only with the duration of depression. High bone metabolism turnover was found with a predomination of osteoresorption which, but not osteosynthesis, correlated with the severity of depression, estimated through Hamilton depression scores. Despite higher but not significant levels of cortisol in women with unipolar depression, the BMD decrease and high bone turnover seem not to be the consequence of hormonal changes or medical treatment. The significant correlations between physical activity and osteoresorption markers were found indicating possible underlying mechanism.

Conclusions: Premenopausal women with unipolar depression have significantly lower BMD because of stimulated bone cell metabolism with predomination of osteoresorption process, mostly due to decreased physical activity in depression. These women should be investigated for osteoporosis and the multidisciplinary team approach is advocated.
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http://dx.doi.org/10.1016/j.bone.2007.11.010DOI Listing
March 2008

Comorbidity of schizophrenia and cancer: clinical recommendations for treatment.

Psychiatr Danub 2006 Jun;18(1-2):55-60

Institute for Psychiatry, Clinical Centre of Serbia, Belgrade, Serbia and Montenegro.

The paper analyzes some issues on the comorbidity between schizophrenia and cancer. Epidemiological studies have reported contradictory results, but it is certain that patients with schizophrenia are more likely to suffer from risk factors for cancer development, such as increased alcohol abuse, obesity, nicotine dependence and decreased physical activity. The paper gives guidelines for the treatment of cancer in patients with schizophrenia, and discusses possible interactions between chemotherapy and psychotropic drugs. Particular attention is paid to the use of antipsychotics which increase the level of prolactin, in view of the possible risk of breast and endometrial cancer in patients with schizophrenia.
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June 2006

Carbamazepine for acute psychosis with EEG abnormalities.

Vojnosanit Pregl 2004 Jul-Aug;61(4):399-403

Clinical Center of Serbia, Institute for Psychiatry, Belgrade, Serbia and Montenegro.

Aim: To investigate the efficacy of carbamazepine as adjuvant drug therapy in acute paranoid psychosis with associated EEG abnormalities, compared to sole antipsychotic treatment.

Methods: Eleven medication-naive patients, diagnosed with acute paranoid psychosis with associated EEG abnormalities, were divided into two treatment groups: sole fluphenazine group, with flexible dosing of 5-10 mg/day (n=6), and carbamazepine group (n=5) with the addition of carbamazepine (600 mg/day) to fluphenazine treatment. Clinical Global Impression (CGI), Brief Psychiatric Rating Scale (BPRS), Scale for the Assessment of Negative Symptoms (SANS), and EEG were assessed on the baseline and after 6 weeks of treatment. Paired and two-tailed t-tests were used for statistical significance.

Results: All the patients showed significant improvement of mental state after 6 weeks of treatment with no significant differences in CGI, BPRS, and total SANS scores in relation to the therapy with carbamazepine. Nevertheless, after 6 weeks of the treatment, EEG findings were significantly better in carbamazepine group, in relation to the findings from the onset of the treatment, as well as in comparison to sole fluphenazine group.

Conclusion: Although carbamazepine stabilized abnormal brain electrical activities it seemed that the associated EEG abnormalities were not significant for acute psychosis observed. These preliminary results suggested that there was no convincing evidence that carbamazepine was efficient as the augmentation of antipsychotic treatment for patients with both acute paranoid psychosis and EEG abnormalities.
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http://dx.doi.org/10.2298/vsp0404399iDOI Listing
December 2004

The effects of fluoxetine on cognitive functions in animal model of Alzheimer's disease.

Psychiatr Danub 2004 Jun;16(1-2):15-20

Institute of Psychiatry, Clinical Centre of Serbia, Pasterova 2, 11000 Belgrade, Serbia,

Cognitive impairment is the hallmark of progressive neurodegenerative process observed in Alzheimer's disease (AD). Acetylcholine (Ach) deficiency is considered to be one of major factors underlying cognitive dysfunction in AD. Several lines of evidence suggest that sigma receptor ligands can elevate Ach extracellular levels in prefrontal cortex rat brain. Since all selective serotonin reuptake inhibitors (SSRIs) show affinity for sigma receptors, it has been assumed that fluoxetine could improve cognition in AD. The aim of study was to investigate the effects of fluoxetine on learning and memory processes in experimental model of AD in rats. Experiments were carried out on adult male Wistar rats divided into three major groups: intact control, sham-operated and nucleus basalis-lesioned rats. Bilateral electrolytic lesions of nucleus basalis Meynert (NBM) (experimental model of AD) were made by 1 mA direct current passed through unipolar electrode for 30 sec. The behavioural test (active avoidance) was performed after recovery period of 10 days from the lesion. The effects of several doses of fluoxetine (3, 5 and 10 mg/kg) on these processes were investigated after 7 days of administration. The results showed that lesion of NBM in rats markedly impaired learning and memory processes compared with controls (intact and sham). Fluoxetine in 5 mg/kg daily doses significantly improved (p<0.05) these processes in lesioned animals. These findings suggest that fluoxetine could be useful as symptomatic therapy in the treatment of AD.
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June 2004

[Correlation of neurodevelopmental disorders in schizophrenia].

Srp Arh Celok Lek 2003 Jul-Aug;131(7-8):294-9

Institute of Psychiatry, Clinical Centre of Serbia, Belgrade.

Contemporary aetiopathogenetic considerations, based on neuro-imaging, genetic and developmental neurobiology studies, suggest neurodevelopmental origin of schizophrenia. Several lines of evidence including structural abnormalities on in vivo brain imaging, the excess of prenatal and obstetric complications and the association of congenital and minor physical anomalies with schizophrenia, strongly indicate the neurodevelopmental pathogenesis of schizophrenia. On the other hand, controversial concept of psychotic continuum suggests schizophrenia and depression sharing the same genetic contribution to the pathogenesis. If this would be the case, depression could also be considered as neurodevelopmental disorder. The aims of the study were to investigate the association between: a) pregnancy and birth complications (PBC), and b) minor physical anomalies (MPA) and schizophrenia or depression. Experimental groups consisted of 60 schizophrenic, 28 major depression patients and 30 healthy controls. All patients were diagnosed according to DSM-IV. Schizophrenic group was divided with regard to PANSS score into positive (n = 32) and negative form (n = 28) subgroups. PBC informations were gathered from maternal recall while MPA were examined by using Waldrop scale for adults. The results showed that negative and positive schizophrenic subgroups had significantly more PBC than depressive group (p < 0.05), as well than controls (p < 0.001; p < 0.05; respectively). There was nonsignificant trend for more PBC in negative than in positive subgroup. All schizophrenic patients had higher rates of MPA than depressives (p < 0.05). This trend for more MPA was not significant in comparison with healthy controls. These findings suggest that schizophrenia, especially its negative forms, could be considered as a member of the spectrum of neurodevelopmental disorders, which does not seem to be the case with depression. PBC and MPA could also be valuable in evaluation of risks for schizophrenia and possible predictive indicators of its development.
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http://dx.doi.org/10.2298/sarh0308294iDOI Listing
February 2004

Dementia paralytica (neurosyphilis): a clinical case study.

World J Biol Psychiatry 2003 Jul;4(3):135-8

Institute of Psychiatry, University Clinical Centre, 11000 Belgrade, Pasterova 2, Yugoslavia.

This study reminds clinicians that syphilis presents in many guises. Wars, migration and sexual promiscuity prepare the ground for its return as an important cause of neurological and psychiatric syndromes. Our patient's diagnosis was not suspected at earlier admission. Stage III spirochaetosis was improved by high dose penicillin.
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http://dx.doi.org/10.1080/15622970310029908DOI Listing
July 2003
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