Differentiating Stages of Bipolar and Unipolar Depression-The Possible Role of sICAM-1 and sVCAM-1.

Increased immune-inflammatory activation has been repeatedly linked to etiopathogenesis and the progression of both major depressive disorder (MDD) and bipolar depression (BD). We explore the role of soluble intercellular cell adhesion molecule-1 (sICAM-1) and soluble vascular cell adhesion molecule-1 (sVCAM-1) in diagnostic differentiation and disorder progression in patients with MDD and BD. Serum levels of sICAM-1 and sVCAM-1 were measured in 137 patients (MDD = 93 and BD = 44) and compared with 73 healthy controls. The severity of psychopathology was assessed using the Hamilton Depression Rating Scale and Clinical Global Impression Scale. After adjustment for multiple confounders, we noticed significant downregulation of sVCAM-1 and upregulation of sICAM-1 levels in both patient groups. Decreased sVCAM-1 levels were detected in patients with acute episodes of BD when compared to MDD. Immune mediators were related to indicators of progression in both mood disorders. They also followed different post-treatment normalization patterns in MDD and BD and in relation to the stage of each disorder. Adhesion molecules could potentially be useful in discriminating between patients with MDD and BD and determining the possible progression of the disorders. Future nosological methods should include time-dependent pathoplasticity and biological correlates, at least for affective disorders.

For Those Who Fight, Fall and Raise Again - Impact of COVID-19 Pandemic on Mental Health of Health Care Providers.

BACKGROUND: During the COVID-19 pandemic health care providers found themselves under increased demands in the work environment and in their professional and personal lives which created both physical and mental health challenges. Thus, we aim to provide an integrative review that identifies and summarizes the research published regarding mental health functioning in health care providers, in Serbia, since the beginning of the pandemic. SUBJECTS AND METHODS: A search of the published literature was conducted using Medline and SCIndex databases, applying key words "COVID-19" and "Serbia". The search was limited to papers published since the beginning of the COVID-19 pandemic until January 2022. Two reviewers independently screened the retrieved papers. The study used pre-defined inclusion and exclusion criteria. RESULTS: We identified eight papers on the subject of mental health functioning in health care providers. The studies were all original research papers with predominantly cross-sectional study design, using online assessments. Sample size varied in number of participants and profile of medical providers (physicians, nurses and medical technicians, community pharmacists). Dominantly, focus of interests of researchers were exploration of levels of anxiety, depression, sleep disturbances, burnout, as well as behavioural changes and environmental influences. CONCLUSIONS: The studies related to mental health of medical professionals show the importance of recognizing the psychological challenges posed by health crises caused by COVID-19. They raise awareness of recognizing differences and difficulties between wide range of medical sectors, and appeal for necessity for accessible and professional psychological support. Further studies should address the detailed exploration of the mental health of this specific population, as well as propose strategies needed to balance the challenges posed by the pandemic.

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

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.

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

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.

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.

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.

Cannabis and psychosis revisited.

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.

Algorithms in psychiatry: state of the art.

INTRODUCTION: In literature, algorithms (guidelines) are often synonymous with problem-solving procedures. The importance of using algorithms in psychiatry can be seen in many areas. For physicians, algorithms ease clinical decision making, provide an adequate clinical basis for therapy, stimulate research, and stimulate sources of financing. For users of psychiatric services, algorithms tailor treatment to the individual, enhance the standard of care by using efficient therapeutic techniques, improve outcome, cut costs, and provide continuity of care after hospital treatment. AIM: Our goal with this paper is to present the advantages of using algorithms, but also to advise caution in their application. It is important to be aware and critical of limitations present in algorithm use. METHODS: A MEDLINE and KOBSON search was conducted combining the following key words and phrases: "treatment guidelines"; "algorithms"; "psychiatry"; "bipolar"; "depression"; "schizophrenia". RESULTS: We investigated the advantages and disadvantages of algorithms presented in the publications we found in our search. CONCLUSION: We consider algorithms to be a necessary component in the treatment of psychiatric patients, but recommend that one should maintain a critical attitude and remember that guideline proposed therapy should always be tailored to the individual.

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

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.

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.

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

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.

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

Critical review of studies on quality of life in psychiatric patients published in Serbian medical journals from 2000 to 2009.

BACKGROUND: Quality of life (QoL) is known to be indicative of the level of social functioning in mental health patients. However, the research on QoL, in the field of psychiatry, is not as comprehensive as it is in other domains of medicine. The aim of this study was to review the research evidence on QoL in psychiatric patients, published in Serbian medical journals during the last decade. MATERIAL AND METHODS: The research data from studies on quality of life in psychiatric patients, published in Serbian medical journals from 2000 to 2009, were obtained by searching the databases Kobson and Medline. RESULTS: We found eight studies on QoL in psychiatric patients published in Serbian medical journals from 2000 to 2009. The reviewed articles were focused on the comparison of QoL between psychiatric patients and healthy controls, or somatic patients, the research on the relationship of QoL and general psychopathology, and the research on QoL and medical treatment. CONCLUSIONS: QoL in patients suffering from mental disorders, as the outcome variable, is of a paramount interest in the follow-up treatment studies in psychiatry targeting critical issues of mental illness management strategies. QoL of psychiatric patients in Serbia is still under-researched, and it would be important to measure QoL from both a patient's and observer's (i.e. family members, friends, nursing staff, mental health professionals, etc.) perspective, in the context of social, economic, and cultural background of the patient. In the future, the studies on QoL in psychiatric patients in Serbia should also rely on "disease specific" assessment scales, which would consider particular aspects of psychopathology, and eventually follow up longitudinal course of mental illness, treatment outcome, and recovery.