Abstract Depression represents a mood disorder and is considered to be one of the most common mental disorders in general. World Health Organization estimates that depression will be the leading cause of disability-adjusted life years, until 2030. Depression is a complex heterogeneous disorder where immune system and its regulation play an important role. Innate and adaptive immunity mechanisms are included, along with processes of immune activation and suppression. The expression of humoral factors of innate immunity, especially pro-inflammatory cytokines, is increased, whereas the intensity of cellular immune mechanisms, primarily T cells and NK cells, are impaired. The influence of pro- inflammatory cytokines on depression is reflected in their effect on certain enzymes and ensuing reduction of neurotransmitters serotonin and dopamine. They also affect the neuroendocrine function in central nervous system, resulting in increase of cortisol levels and inactivation of glucocorticoid receptors in the periphery, which leads to neurodegeneration and decrease in neurotransmitter production. Certain cytokines affect neuroplasticity through the decreasing of concentration of neurotrophic brain factor and induction of brain cell apoptosis. The results are often contradictory talking about mechanisms of adaptive immunity. On one hand, an increased activity of Tlymphocytes is observed, while on the other, there are evidence of spontaneous apoptosis and impaired function of these cellsin depression. In addition, neuroprotective role of autoreactive and regulatory T cells in prevention of depression has also been demonstrated. The aim of this paper is to analyze the current knowledge on the role of immune mechanisms in the pathogenesis of depression.

Tryptophan (TRP) catabolites exert neuroactive effects, with the plethora of evidence suggesting that kynurenic acid (KYNA), a catabolite of the kynurenine pathway (KP), acts as the regulator of glutamate and acetylcholine in the brain, contributing to the schizophrenia pathophysiology. Newer evidence regarding measures of KP metabolites in the blood of schizophrenia patients and from the central nervous system suggest that blood levels of these metabolites by no means could reflect pathological changes of TRP degradation in the brain. The aim of this study was to investigate plasma concentrations of TRP, kynurenine (KYN) and KYNA at the acute phase and remission of schizophrenia in a prospective, case-control study of highly selected and matched schizophrenia patients and healthy individuals. Our study revealed significantly decreased KYN and KYNA in schizophrenia patients (p < 0.001), irrespective of illness state, type of antipsychotic treatment, number of episodes or illness duration and no differences in the KYN/TRP ratio between schizophrenia patients and healthy individuals. These findings could be interpreted as indices that kynurenine pathway might not be dysregulated in the periphery and that other factors contribute to observed disturbances in concentrations, but as our study had certain limitations, we cannot draw definite conclusions. Further studies, especially those exploring other body compartments that participate in kynurenine pathway, are needed.

IntroductionThe kynurenine pathway of tryptophan catabolism has come into the spotlight of schizophrenia research since its catabolites exert neuroactive effects. A strong body of evidence suggests that kynurenic acid, a catabolite of kynurenine pathway, acts as the only endogenous NMDA receptor antagonist leading to the weakening of circuits in layer III of dorsolateral prefrontal cortex of schizophrenia patients. Studies exploring the levels of kynurenic acid and other metabolites of tryptophan in peripheral blood did not yield any definite conclusions.ObjectivesPrimary objective of this study was to assess differences in concentrations of key constituents of kynurenic pathway in blood plasma – tryptophan (TRP), kynurenine (KYN) and kynurenic acid (KYNA) between schizophrenia patients (SCZ) and healthy controls (HC). Secondary objective was to explore correlations between these concentrations and clinical characteristics.MethodsIn our two-centre prospective case-control study we measured plasma concentrations of TRP, KYN and KYNA in 36 healthy controls (HC) and 38 schizophrenia (SCZ) patients during acute exacerbation and remission and explored the correlations with clinical parameters using PANSS scale. The patients were matched with HC by age, sex and body mass index and exclusion criteria included obesity class 2 or higher, any concomitant organic mental or neurological disorder, acute or chronic inflammatory disease, and use of immunomodulatory drugs or psychoactive substances.ResultsTRP concentrations were significantly higher in HC than in SCZ patients in acute phase (p&lt;0,001) and remission (p&lt;0,001), while SCZ patients in acute phase had significantly higher TRP levels than in remission (p&lt;0,01). Levels of KYNA and KYN were significantly lower in SCZ patients than in HC both in acute phase and remission, all with high statistical significance (p&lt;0,001). There was no statistically significant difference between acute phase and remission neither for KYN (p&gt;0,05), nor for KYNA (p&gt;0,05). There was no correlation of plasma levels of TRP, KYN and KYNA with total PANSS score, PANSS positive scale score, PANSS negative scale score and PANSS general psychopathology scores, both in acute phase and remission (p&gt;0,05). Also, there was no correlation between plasma levels of TRP, KYN and KYNA in SCZ patients in remission with improvements measured with PANSS scale (p&gt;0,05).ConclusionsAlthough there are concerns about the value of measurement of metabolites of kynurenine pathway in the peripheral blood, our data suggest that significantly decreased levels of KYN and KYNA could suggest that disrupted TRP degradation in SCZ patients may be reflected in the peripheral blood as well. Further studies of peripheral levels of kynurenine pathway metabolites on larger samples should also explore effects of antipsychotic therapy, but also their correlation with other clinical parameters such as neurocognition.Disclosure of InterestNone Declared

The Brief Assessment of Cognition in Schizophrenia (BACS) scale was developed for the assessment of cognitive function in patients with schizophrenia. The objective of this study was to cross-culturally adapt and validate the BACS in to the Serbian language. The study was conducted at the Laza Lazarevic Clinic for Mental Disorders and the Clinic for Psychiatry of the University Clinical Center of Serbia from March 2021 to January 2022. The study enrolled 61 inpatients diagnosed with schizophrenia and 61 healthy controls matched for age and sex. Compared with the healthy control group, the schizophrenia patient group had worse cognitive function in all dimensions measured using BACS (p < 0.001 for all measures). The mean standardized composite BACS score was z = -2.46, and symbol coding (z = -2.54) was the most deficient function. Principal component analysis suggests a two-factor structure, where the first factor consisted of loading the measures of verbal and working memory, attention, speed of information processing, and executive function, while the second factor regarded the loading of motor speed. Cronbach's alpha coefficient demonstrated an excellent level of internal consistency (0.798). These outcomes suggest that the Serbian BACS neurocognitive battery's psychometric properties are satisfactory, with good overall discriminant validity and high internal consistency. The Serbian BACS appears to be a quick and reliable neuropsychological instrument for evaluating global cognition in schizophrenia patients in Serbia.

Background/Aim. There is no available published data about the use of long-acting injectable paliperidone palmitate (PP) in schizophrenia patients in the Republic of Serbia. The aim of this study was to assess hospitalization rates be-fore and after the switch to once-monthly long-acting injectable PP in schizophrenia patients, as well as their compliance with this drug. Methods. We conducted a retrospective cross-sectional study in which hospitalization rates were evaluated 12 months before and 12 months after the switch to once-monthly long-acting injectable PP in 113 schizophrenia patients. The age of the enrolled patients was between 18 and 66 years. Results. The average age of the enrolled patients was 38.36 ? 11.62 years. Among them, 77 (68.1%) were male, and 36 (31.9%) were female. Out of the total number of 113 patients treated with once-monthly injectable PP, 78 (69.03%) were on monotherapy, while 35 (30.97%) had one additional oral antipsychotic (risperidone, olanzapine, aripiprazole, or clozapine). Out of the total number of 113 patients, 68 (60.18%) were not hospitalized in the 12-month period before the switch to once-monthly long-acting injectable PP, while 45 (39.82%) were hospitalized in the same period. Given that 8 patients out of the total number of 113 were excluded from therapy due to an adverse event or their own decision in the period after the switch to PP, the analysis of the hospitalization rate after the switch to PP was performed for the remaining 105 patients, of which 9 (8.57%) were hospitalized in the period after the switch to PP, and 96 (91.43%) were not. Conclusion. Our results show high compliance in the treatment with once-monthly injectable PP and a positive impact of treatment with this drug on low hospitalization rate in a 12-month period in patients with schizophrenia. Considering the availability of this drug in the Republic of Serbia, these results encourage the use of once-monthly injectable PP as an important therapeutic option in schizophrenia patients.

Introduction/Objective. Mild cognitive impairment (MCI) is a state of progressive cognitive decline, rarely recognized by general practitioners (GPs), which is a reason of late treatment and fast progression towards more serious conditions. The main obstacles for the timely treatment of MCI are lack of diagnostic protocols and clinical guidelines as well as lack of knowledge and disbelief in the pharmacological therapeutic possibilities. The aim of this investigation was to assess level of recognition of MCI symptoms by GPs, and to estimate their perception of distinct risk factors significance for MCI development. Methods. Participants of the ?Days of General Medicine? Conference (Serbia, March 2018), n = 340, completed 12 items questionnaire about recognition and treatment of the MCI patients. We have used descriptive statistics, ?2, Mann?Whitney U tests, binary logistic regression analysis for results presentation, sub-groups comparison, to assess predictors of drug therapy selection, respectively. Results. Study showed GPs recognize diabetes as most important factor for MCI, then hypercholesterolemia, smoking and sedentary behavior, while hypertension and obesity are perceived as less important. Those GPs who estimated diabetes and hypercholesterolemia as more important for all patients are significantly more prone to prescribe symptomatic therapy (pentoxifylline and vinpocetine), p &lt; 0.05 according to ?2 test. Logistic regression analysis regarding therapy predictions showed that years of GP experience is the most important predictor of drug therapy selection (p &lt; 0.01). Conclusion. Results of this investigation pointed a need for MCI education for young physicians, in order to improve diagnosis and treatment of these patients.

Many adolescents worldwide have the problem of meeting recommended nightly sleep hours. The causes of sleep disturbance are multifactorial, but interest in food’s effect on sleep has dramatically increased lately. In this study, we investigated the association between regular energy drink (ED) intake (weekly or more frequent) and sufficient sleep (SS) (≥8 h) in adolescents. Additional objectives were to examine the relationship between health-related behaviors and SS, stratified by gender. A population-based cross-sectional study was conducted during the 2019/2020 school year from 12 schools in Belgrade. There were 1287 students aged 15 to 19 who participated (37.4% male). We used a modified version of the food frequency questionnaire adapted for Serbian adolescents. Logistic regression revealed that regular ED consumption was an independent risk factor negatively related to SS in both sexes. Additionally, daily vegetable and water intake (≥2 L) showed a positive correlation with SS in boys, while in girls, the odds of realizing SS decreased with statements of sedative use. In conclusion, we show that ED intake is negatively associated with SS in both sexes; daily vegetable and water intake (≥2 L) may raise the odds of SS in boys, while sedative use may decrease the chances of SS in girls.

Abstract Non suicidal self-injury is defined as intentional self-inflicted injury without the intent to die. Suicide attempt is defined as a nonfatal, self-directed, potentially injurious behavior with the intent to die. Although distinct behaviors, they are frequently associated and possibly clinically related. The aims of this study are to explore demographic data, social-demographic differences between genders, co-occurrence of non-suicidal self-injuries with suicide attempt, their association with gender and clinical variables. Retrospective cohort study on 143 patient admitted in Clinic for mental disorders „Dr Laza Lazarevic“, aged 14 to 18 years, between January 2015 and January 2016. Information were obtained from database and included two categories of variables: socio-demographic (age, gender, education level, current living situation) and clinical variables (abuse, neglect, peer violence, aggressive behavior, non-suicidal self-injuries, suicide attempt and others). The mean age of adolescents was 15.8 years, with female being more frequent in the sample (51.4%). The incidence of Mood disorders was significantly higher (p&lt;0.05) in female compared to male (χ²꞊3,96, df꞊1, rC꞊0.16, p꞊0.04). A significantly higher incidence (p&lt;0.05) of non-suicidal self-injury (χ²꞊11.15, df꞊1, rC꞊0.27, p꞊0.001) and suicide attempt was found in female compared to male (χ²꞊5.38, df꞊1, rC꞊0.19, p꞊0.02). No statistically significant difference was found in their simultaneous occurrence compared to total population of hospitalized adolescents. The findings of the present study demonstrated that non-suicidal selfinjury and suicide attempt occur in clinical population of adolescent more often among female then in male adolescents.

IntroductionSchizophrenia spectrum disorders may severely limit ability to achieve and maintain gainful employment of affected working-age individuals.ObjectivesAssess the employment status in patients with schizophrenia spectrum disorders treated with long acting injectable paliperidone palmitate after the switch from oral antipsychotics.MethodsA single centre mirror image design study of 115 patients with schizophrenia spectrum disorder was conducted in a tertiary level psychiatric hospital. Data were collected for period of 12 months prior toand 12 months after switching from oral antipsychotic to long acting injectable paliperidone.Employment status for 6 enrolled patients was missing.ResultsMean age of enrolled patients was 38,4±11,6 years. Of the 109 patients analyzed for employment status, 44,4% remained employed for 12 months after switching to long acting injectable paliperidone while 4,6% patients changed their employment status from unemployed to employed after the switch. No patient changed their employment status from employed to unemployed after the switch. 9,2% patients were already retired at the beginning of study period and 5,5% of patients maintained their student status. 36,7% patients remained unemployed for the whole study period. The correlation between employment status of employed and unemployed patients and duration of illness was borderline significant with p=0,049.ConclusionsThe data from this study suggest that use of long acting injectable paliperidone contributed to preservation of working ability of working-age patients suffering from schizophrenia spectrum disorders.DisclosureNo significant relationships.

Problematic mobile phone use can be related to negative mental states. Some studies indicate that behavioural dependency is related to variables associated with the country of origin. The aim of our study was to investigate if country indicators moderated the relationship between phubbing and psychological distress. Our sample consisted of 7,315 individuals from 20 countries, who completed the Phubbing Scale and the Kessler Psychological Distress Scale (K6). The analyses also included country indicators: the Gender Gap Index (GGI), the Human Development Index (HDI), the Social Progress Index (SPI), Hofstede’s dimensions of culture, and the World Happiness Index (WHI). Our results showed that psychological distress was related to at least one dimension of phubbing (i.e., to communication disturbance or phone obsession) in all countries, which means this relationship is culturally universal. The results of the study demonstrate the importance of testing measurement invariance to determine what type of analysis and what type of conclusion are valid in a given study or comparison. Moreover, the increasing or decreasing correlation between phubbing and distress is related to some culture-level indices.