Bojana Dunjić-Kostić

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

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.

Neutrophil-to-lymphocyte ratio predicting suicide risk in euthymic patients with bipolar disorder: Moderatory effect of family history

BACKGROUND Neutrophil-to-lymphocyte ratio (NLR) has been independently related to bipolar disorder (BD) and factors associated with suicidal risk. The aim of our study was to explore the relationship between NLR and suicide risk in euthymic BD patients. We also sought to propose a model of interaction between NLR and stress-diathesis factors, leading to suicidal risk in BD. METHODS The study group consisted of 83 patients diagnosed with BD (36 suicide attempters; 47 suicide non-attempters), compared to the healthy control group (n=73) and matched according to age, gender, and body mass index (BMI). NLR was measured according to the complete blood count. Mood symptoms have been assessed by Young Mania Rating Scale and Montgomery-Asberg Depression Rating Scale. Early trauma and acute stress were evaluated by Early Trauma Inventory Self Report-Short Form and List of Threatening Experiences Questionnaire, respectively. Suicide risk has been assessed by Suicide Behaviors Questionnaire-Revised (SBQ-R). RESULTS Significant correlation was found between NLR and SBQ-R score. The main effects of suicide attempts on NLR, after covarying for confounders, were observed, indicating increased NLR in BD suicide attempters compared to healthy controls. We found significant moderatory effects of family history on NLR relationship to suicidal risk, with NLR being significant positive predictor of suicidal risk only in the patients with positive family history of suicide attempts. CONCLUSIONS The results suggest an enhancing effect of positive family history of suicide attempts on predictive effect of NLR on suicide risk. Our data support the idea that immune markers can predict suicide attempt risk in BD, but only in the subpopulation of BD patients with family history of suicide attempts. This could lead to prevention in suicide behavior in the patient population at particular risk of suicide.

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

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.

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

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.

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

Abstract In the last two decades, Serbia has had to deal with multiple social and economic problems reflecting on societys 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.

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

Abstract 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.

Acute and Long-term Overall Severity of Bipolar Disorder Related to Sicam-1 and Svcam-1 Serum Levels in Bipolar Depression

Introduction Interplay between nervous and immune systems plays an important part in clinical presentation and course of affective disorders. Aims The aim of the study has been to assess the relation between soluble vascular cell adhesion molecule-1 (sVCAM-1) and soluble intercellular cell adhesion molecule-1 (sICAM-1), in acute and remission phase of bipolar depression, in regard to acute and long-term measures of overall severity of the bipolar disorder. Methods The study has explored serum levels of sVCAM-1 and sICAM-1 in 43 patients with bipolar depression. The adhesion molecules’ levels of patient group have been analyzed in acute and remission phases, in regard to bipolarity index (BPIX) and in regard to global functioning (measured by Global Assesment of Functioning Scale- GAF) Results The acute serum levels of sICAM-1 have been associated to BPIX. Moreover, sVCAM-1 serum selevels have been associated to BPIX in both phases of the disorder. In addition, acute sVCAM-1 levels have been associted to GAF score in accute phase. Conclusions Our results suggest that cellular adhesion is an important factor in clinical presentation and overall severity of bipolar disorder.

2340 – The role of age and gender in predicting serum levels of IL-6 and TNF-α in patients with schizophrenia and major depression

Introduction Growing evidence in the field of psychoneuroimmunology indicates an interconnection between psychiatric disorders, in particular schizophrenia and mood disorders, and cytokine alternations. Gender and aging are commonly reported to affect cytokine levels, but contrasting conclusions still represent a topic for debate. Objectives and aims Our aim was to investigate the role of age and gender in the serum levels of Interleukin-6 (IL-6) and Tumor Necrosis Factor-alpha (TNF-α), in patients with schizophrenia (SCH) and major depression (MDD). Method We measured serum levels of IL-6 and TNF-α in acute exacerbation of illness, in 37 patients with MDD, and compared them to 43 patients with SCH. The serum levels were measured by the enzyme-linked immunosorbent assay (ELISA). All patients fulfilled the ICD-10 criteria. Results The significant interaction between gender and psychiatric disorders on serum cytokine levels, and the association between IL-6 and TNF-α and age, in both groups of patients, were not detected. However, when applied the linear regression model with the serum cytokine levels as dependant variable, and age, gender, and psychiatric disorder as independent variables, the significant predictive effect of age on levels of both investigated cytokines was detected. The patients over 35 years of age had higher levels of IL-6 and even significantly lower levels of TNF-α, regardless of the diagnosis. Conclusion The results suggest that the aging process could be a relevant factor influencing the immune status of patients with SCH and MDD. Further prospective studies are essential to further investigate biological mechanisms that underlie these multidimensional interconnections.

P02-502 - Postpartal psychosis: Serbian experience

Introduction Childbirth and the postpartal period present a form of specific maturational crisis and an extremely vulnerable period for every woman, especially for those who have potential for some psychological disturbances. Aim We explored sociodemographic and clinical manifestations of women in the postpartal period who were hospitalized at the Institute of Psychiatry, Clinical Center of Serbia. Method This retrospective study included 60 patients with psychiatric disorders developed within six months after childbirth. Inclusion criteria were: negative psychiatric hystory, negative history of puerperal episode, and postpartal disorder as a first manifestation of psychiatric disturbances. Patients were diagnosed according to RDC criteria (research diagnostic criteria). Results Patients with psychotic features were predominant, average age 23.6; married; mothers of male offspring and with positive family history of psychiatric disorders in 30%. Subacute development of clinical manifestations was noticed, 3.5 weeks after childbirth on average. No psychopathology was observed before third postpartal day. Obstetric manifestations did not influence psychopathology. Conclusion Childbirth is a significant risk factor for the expression of mental dysfunction in the puerperal period. The most vulnerable group is women with clinical expression of dysfunction, specific sociodemographic characteristics, and positive family history of psychiatric disorders.