Genetic predisposition of suicidal behavior: variants in GRIN2B, GABRG2, and ODC1 genes in attempted and completed suicide in two Balkan populations.

Completed suicide accounts for over 700,000 deaths worldwide annually, while attempted suicide is 20 times more frequent. Genetic background is an important factor contributing to suicidal behavior, including candidate genes in glutamate, γ-aminobutyric acid (GABA), and polyamine systems. Our aim was to differentiate genetic predispositions underlying different types of suicidal behavior, attempted and completed suicide, in two Balkan populations. Analysis of variants in the genes GRIN2B (rs2268115 and rs220557), GABRG2 (rs424740), and ODC1 (rs1049500 and rs2302614) was performed on a study sample including 173 suicide attempters with comorbid psychiatric disorders, 216 non-suicidal psychiatric patients and 172 healthy controls from Serbia, and 333 suicide completers and 356 non-suicidal autopsy controls from Slovenia. CA genotype of rs220557 in GRIN2B gene increased the risk for completed suicide (P = 0.021), and violent suicide (P = 0.037), compared to controls. In ODC1 gene, CA genotype of rs2302614 decreased the risk for completed suicide compared to suicide attempt (P = 0.012). Marginally, AC haplotype for variants rs1049500-rs2302614 in ODC1 gene decreased the risk for completed suicide compared to suicide attempt (P = 0.052). Specific genetic variants of glutamate and polyamine systems are differently distributed among diverse suicidal phenotypes, providing further information on the implication of these systems in suicidality.

Mood disorders and 5-HTR2A genetic variants - the moderator effect of inflammation on expression of affective polarity phenotype.

BACKGROUND: Although repeatedly confirmed, the molecular nature of gene-environment (GxE) interactions has rarely been investigated in the clinical context of mood disorders. This study assesses the relationship between HTR2A genetic variants and the modulatory effect of inflammation in a collective cohort of patients with major depressive disorder (MDD) and bipolar disorder (BD), as a unified group with two distinct phenotypes. METHODS: The study included 138 patients with acute mood episodes (BD = 83; MDD = 55). HTR2A rs6313 and rs6314 genotyping was performed while measuring platelet-derived indicators of inflammation (platelet count (PLT), mean platelet volume (MPV), plateletcrit, and platelet distribution width) and the MPV/PLT ratio. RESULTS: The HTR2A rs6313 variant is a significant predictor of the polarity phenotype in mood disorders, with the MPV/PLT ratio moderating this relationship, but only under low-inflammatory conditions. In more pronounced inflammatory states, genetic influences lose their predictive role. CONCLUSIONS: To our knowledge, this is the first study to investigate the complex interplay between platelet-derived indicators of inflammation and HTR2A variants in the context of mood disorders. Without pro-inflammatory conditions, mood disorders seem to be more genetically determined. Under pro-inflammatory conditions, phenotypic presentation is less dependent on genetic factors. GxE interactions in mood disorders are multifaceted, context-dependent and relevant for assessing their clinical presentation and course.

Alexithymia-A Neglected Factor Influencing Educational Satisfaction and Psychological Wellbeing in Medical Students.

ABSTRACT: Alexithymia presents a reduced ability to identify, express, and describe one's own emotions. In medical professionals, alexithymia is associated with increased burnout and substance use, as well as reduced altruistic behavior. Our aim was to examine the association between alexithymia and different sociodemographic, psychological, and somatic parameters among medical students. Participants included 186 third- and sixth-year students of the Faculty of Medicine in Belgrade, Serbia. Data were collected through an online survey, composed of 1) a general questionnaire (sociodemographic data, education satisfaction, grade point average, presence of psychological and somatic disorders), 2) Twenty-Item Toronto Alexithymia Scale, 3) Patient Health Questionnaire-9, and 4) Beck Anxiety Inventory. Third-year students had significantly higher rates of alexithymia compared with sixth-year students. Negative correlation was found between alexithymia and educational satisfaction ( r = -0.276**) and alexithymia and grade point average ( r = -0.186*). A positive correlation was found between alexithymia and depression ( r = 0.424**) and alexithymia and anxiety ( r = 0.338**). The negative impact of alexithymia on educational satisfaction and psychological health is pronounced in the population of medical students, indicating a need for preventive programs aimed in medical schools.

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.

The Sexuality of Sex Workers: Sexual Arousability and the Sexual Profile of Women Engaged in Prostitution in Serbia.

BACKGROUND: In a view of sex work being a sexual behavioural activity, the main objective of our research was to explore the sexuality of sex workers in Serbia regarding to intensity of their sexual arousability. SUBJECTS AND METHODS: The research was conducted on 30 sex workers and 30 controls of randomly selected social and demographic characteristics, without any signs of psychiatric morbidity. For the evaluation of the intensity of sexual arousability, SAI (Sexual Arousability Index) questionnaire was used. RESULTS: The analysis of the main total scores of the SAI for the sex workers and control participants showed no statistically significant difference in the overall intensity of arousability (p>0.05). However, item by item analysis of the questionnaire showed qualitative difference in sexuality between sex workers and controls, related to certain aspects of sexuality. CONCLUSIONS: These findings allow the space for further research in the way of identifying origins of qualitative issues in the sexual profile of sex workers, in correlation to women who are not sex workers, i.e. whether they had been result of potential biological, specific psychodynamic factors, or have been formed as a result of the direct influence of the sex work.

Effect of childhood general traumas on suicide attempt depends on TPH2 and ADARB1 variants in psychiatric patients.

Suicidal behavior has been associated with a deficient serotonin neurotransmission which is likely a consequence of individual genetic architecture, exposure to environmental factors and interactions of those factors. We examined whether the interaction of child abuse, TPH2 (tryptophan hydroxylase 2) variant rs4290270, affecting alternative splicing and editing of TPH2 pre-mRNAs, and ADARB1 (adenosine deaminase acting on RNA B1) variants rs4819035 and rs9983925 may influence the risk for suicide attempt in psychiatric patients. TPH2 rs4290270 was genotyped in 165 suicide attempters and 188 suicide non-attempters diagnosed with major depressive disorder, bipolar disorder and schizophrenia. Genotyping data for ADARB1 variants were taken over from our previous study. Child abuse before the age of 18 years was assessed using the Early Trauma Inventory-Self Report. Generalized linear models and backward selection were applied to identify the main and interacting effects of environmental and genetic factors, including psychiatric diagnoses, patients' gender and age as covariates. Childhood general traumas were independently associated with suicide attempt. Two-way interaction between TPH2 rs4290270 and general traumas revealed that TT homozygotes with a history of general traumas had an increased risk for suicide attempt. Three-way interaction of general traumas, TPH2 rs4290270 and ADARB1 rs4819035 indicated that the highest predisposition to suicide attempt was observed in individuals who experienced general traumas and were TT homozygote for rs4290270 and TT homozygote for rs4819035. Our findings suggest that the risk for suicide attempt in psychiatric patients exposed to an adverse childhood environment may depend on TPH2 and ADARB1 variants.

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.

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.

Exploring the role of TNF-α, TGF-ß, and IL-6 serum levels in categorical and noncategorical models of mood and psychosis.

Psychotic and mood disorders are discussed as part of the same continuum. The potential role of immune dysregulation in defining their clinical presentations, however, remains unclear. Differences in TNF-α, IL-6 and TGF-ß levels were investigated in 143 patients with schizophrenia (SCH = 63) and bipolar disorder (BD = 80), in remission. Cytokines were evaluated against the dimensional assessment of psychosis and affective symptoms using the schizo-bipolar scale, together with the severity of the same symptom domains measured by the brief psychiatric rating scale (BPRS). Lower TGF-ß was associated with more lifetime episodes, family risk for psychosis, and more severe mood and psychotic symptoms in all patients. BPRS Affect symptoms domain correlated with lower TGF-ß levels in BD, and higher TGF-ß levels in SCH patients. Using moderated mediation analysis, TGF-ß was a relevant predictor only in the setting of non-categorical symptom distribution, with familial risk for psychosis confirmed as a significant moderator. Severity of BPRS Affect symptoms domain was an independent predictor of inclination towards the psychosis spectrum. The underlying immune dysregulation may be shared by the disorders, rather than a unique characteristic of each, having significant implications for our understanding of the continuum vs. categorical approach to psychosis and mood disorders.

COPD and Depression Analysis in Regard to Obstructive Pulmonary Levels.

Depression symptoms take place recurrently in patients suffering from COPD. This study aims to assess the effects of antidepressant therapy in patients with COPD and a depressive disorder in relation to COPD levels. The study population consisted of N = 87 patients diagnosed with COPD, according to the GOLD criteria, and a depressive disorder. All of the patients were subjected to clinical and psychiatric exploration according to psychiatric assessment instruments, which was followed by SSRI therapy for the duration of 8 weeks. The main methods used were descriptive statistics and analysis of variance. The results showed a different distribution of depressive symptoms at a different stage of COPD by FEV1 (χ2 = 30.47, df = 6, p < 0.01) and by mMRC (χ2 = 34.6, df = 6, p < 0.01). After the application of SSRIs, there was a significant improvement in HDRS scores in all stages of COPD by FEV1 (χ2 = 251.62, df = 9, p < 0.01) and by mMRC (χ2 = 919.17, df = 9, p < 0.01). This study contributes to the improvement in the quality of life of patients by the targeted application of SSRI therapy and, therefore, more precise and better overall treatment results.

Anxiety in patients treated in a temporary hospital in Belgrade, Serbia, during the first epidemic wave of COVID-19.

Background: It has been reported that COVID-19 patients in general often experience anxiety, depression and stress, but those problems in patients of temporary COVID-19 hospitals seem to have attracted less attention. Methods: The study included 87 SARS-Cov-2 infected subjects accommodated and treated in a temporary hospital in Belgrade, Serbia, during the first epidemic wave of COVID-19. The patients' level of anxiety was assessed on two occasions (at admission to the temporary hospital, and 2 weeks after discharge) using the Hamilton Anxiety Rating Scale (HAM-A). Demographic and clinical data were obtained through questionnairesor retrieved from patients' medical records. Results: A multiple linear regression model revealed that sex, age, the severity of COVID-19 symptoms (COVID-19_SS) and the family history of psychiatric disorder (FHPD) remain significant predictors of the level of anxiety at hospital admission (F (4, 82) = 14.916, p < 0.0001), wih an R2 of 0.421. Participants' predicted level of anxiety at admission to the temporary COVID-19 hospital can be calculated as 0.931-0.708 × SEX +0.029 × AGE +0.674 × COVID-19_SS + 1.491 × FHPD, where SEX is coded as 1 for male and 0 for female, AGE is measured in years, COVID-19_SS is coded as 0 for asymptomatic, 1 for mild, 2 for moderate and 3 for severe, and FHPD as 0 for negative and 1 for positive. Comparison between individual HAM-A score at admission to the temporary hospital (median (IQR): 7.00 (2.00-11.75)) and 2 weeks after discharge (median (IQR): 0.00 (0.00-1.00)) revealed significant reduction in the level of anxiety among study participants (Z = -7.53, p < 0.001). Conclusion: These data indicate that psychological changes exist in those hospitalized in temporary hospitals, but that they regress soon after they leave.

Research by Psychiatric Trainees and Early Career Psychiatrists-Results of a Survey From 34 Countries in Europe.

Clinical psychiatric practice should be intricately linked with research work. Although psychiatric trainees and early career psychiatrists (ECPs) are in the frontline of clinical services, little is known about how much access they have to research opportunities. A semi-structured questionnaire of 35 questions-exploring research goals achieved, facilitators and barriers as well as personal context-was sent to psychiatric trainees and ECPs across Europe. The survey was disseminated through the local committees of the main professional psychiatric societies in Europe. A total of 258 individuals working in 34 European countries participated. The majority (69.8%) were psychiatric trainees within training in adult psychiatry. Most participants (69.0%) were highly interested in research, but faced major obstacles toward their research activities, such as lack of time and funding. They were highly satisfied with mentoring and publishing papers. Only half of the participants, however, had already published a scientific article, and only a few have been able to contribute to randomized clinical trials (20.9%). A large proportion of participants (87.2%) reported to conduct research after or during a mixture of working hours and after working hours. Only one tenth ever received a grant for their work. These findings highlight that the key barriers for the performance of research are lack of time and funding. Psychiatric trainees and ECPs are motivated to perform research but need support and regular opportunities.

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.

Women, Partners, and Mothers-Migratory Tendencies of Psychiatric Trainees Across Europe.

Introduction: Combining a successful career with family planning has become increasingly important in recent years. However, maintaining a relationship, deciding upon the optimal time for pregnancy and other family planning decisions can still be quite challenging, especially for junior doctors whose training is long and demanding. Currently, women form an important part of the medical workforce, and there is noticeable feminization in migration. However, little is known about the personal characteristics of junior doctors in Europe and how these play a role in their decision to migrate. Methods: Survey of psychiatric trainees in 33 European countries, exploring how personal characteristics, such as gender, relationship status and parenthood, impact their attitudes toward migration. Results: 2,281 psychiatric trainees in Europe took part in the study. In this sample, the majority of psychiatric trainees were in a relationship, but only one quarter had children, although there were variations across Europe. Both men and women indicated personal reasons as their top reason to stay. However, women ranked personal reasons as the top reason to leave, and men financial reasons. Single woman were the most likely of all subgroups to choose academic reasons as their top reason to leave. Interestingly, when women were in a relationship or had children, their attitudes toward migration changed. Conclusions: In this study, a low number of psychiatric trainees in Europe had children, with differences across Europe. These findings raise awareness as to the role of parental conditions, which may be favoring or discouraging parenthood in junior doctors in different countries.

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.

Equal access for all? Access to medical information for European psychiatric trainees.

Access to medical information is important as lifelong scientific learning is in close relation with a better career satisfaction in psychiatry. This survey aimed to investigate how medical information sources are being used among members of the European Federation of Psychiatric Trainees. Eighty-three psychiatric trainees completed our questionnaire. A significant variation was found, and information availability levels were associated with training duration and average income. The most available sources were books and websites, but the most preferred ones were scientific journals. Our findings suggest that further steps should be taken to provide an equal access to medical information across Europe.