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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.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.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.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.

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a hereditary neurological disease accompanied by recurrent ischemic events, characterized by the presence of psychiatric disorders. The aim of this study was to examine the occurrence of depression and its severity among patients with CADASIL. Sixteen patients with diffuse white matter changes on MRI and clinical signs suggesting CADASIL were included in the study. Definitive diagnosis of CADASIL was obtained by electron microscopic analysis of skin biopsies. Testing of the patients’ affective status was primarily devoted to detecting depression. Electron microscopic examinations of all skin biopsies revealed numerous granular osmiophilic material (GOM) deposits embedded into the basal lamina around altered or degenerated vascular smooth muscle cells (VSMCs). Clinical symptoms of depression were present in a great number of examined CADASIL patients. The frequency of depression was higher than previously reported. Psychiatric disturbances might also represent the onset of CADASIL, especially in young patients, and should be evaluated by differential diagnosis. [Projekat Ministarstva nauke Republike Srbije, br. 41002]

It has been shown that bone mass is centrally regulated. Thus schizophrenia being a disease of the central nervous system is an interesting model for studying bone. Most second generation antipsychotic drugs including risperidone are used in the treatment of schizophrenia. Weight gain and metabolic disturbances are common side effects.The aims of this study were to investigate bone mass, body composition and light microscopic pathology examinations of femur in an animal model of schizophrenia (pharmacologically induced by postnatally administered phencyclidine-PCP) and to further examine the effects of chronic treatment with risperidone on these parameters in rats.Four groups of male rats were studied:1) control group-NaCl postnatally administered, n=9; 2) PCP group-postnatal PCP administration to rat pups (on day 2,6,9 and 12), n=6; 3) risperidone group-rats treated with risperidone alone for 9weeks from day 35 (NaCl-RSP group, n=7); 4) PCP rats treated with risperidone for 9weeks from day 35 (PCP-RSP group, n=7). Bone mass and body composition were measured in vivo by dual X ray absorptiometry (areal DXA and fat mass). Light microscopic analysis of the femoral metaphysis was performed in all groups after sacrificing the animals.Postnatal phencyclidine (PCP) administration to rat pups caused a long lasting reduction of total bone mass versus control animals (aDXA 128±2mg/cm(2) vs 139±5mg/cm(2), p0.05). Examination of the femoral bone revealed a decrease in the number and thickness of the metaphyseal trabecule and cortical thinning. There was a decrease in total and retroperitoneal fat. Nine weeks of administration of risperidone alone to rats, resulted in significant weight gain and had no effect on bone mass versus control animals (aDXA was 136±7mg/cm(2) vs 139±5mg/cm(2), p0.05). Furthermore, there were no changes in the light microscopic analysis of femoral metaphysis in comparison with controls. When PCP rats were treated with risperidone, they did not change their body weight nor bone mass versus PCP alone (aDXA 126±2mg/cm(2) vs 128±2mg/cm(2), p0.05) but intriguingly on examination of the femoral bone an increase in the number and thickness of the metaphyseal trabecule was found (trabecular thickness 0.6±0.1μm vs 0.35±0.1μm, p0.01).This study shows that in the PCP rat model of schizophrenia bone mass is reduced. When PCP rats were treated with risperidone bone mass remained unchanged but intriguingly and unexpectedly light microscopic examination of femoral metaphysis showed an increase in thickness of metaphyseal trabeculae. The mechanism of risperidone's action on bone remains to be clarified.

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.

Diabetes mellitus is a major health and social problem. The prevalence of diabetes for all age groups worldwide was estimated to be 2.8% in 2000 and 4.4% in 2030 . Type 2 diabetes mellitus (DMT2) (adult-onset diabetes) is the most common form of this disease, which is present in 90–95% of patients . In Serbia, the prevalence of DMT2 in the year 2000 was 4.5%, both in men and women . Diabetes has negative impact on physical, psychological and social functioning . DMT2 is a disease related to stress and stressful life events which may have an important role in its pathogenesis, course and outcome. The interactions between behaviour, central nervous and endocrine systems that might cause immunosuppression is the most fascinating finding in modern medicine, and its implications are important for the prevention and treatment of somatic illnesses . The patophysiological mechanisms related to the role of stressful life events on the emergence of DMT2 include hypothalamic arousal syndrome, with parallel activation of the hypothalamic-pituitary-adrenal axis (HPA) and the central sympathetic nervous system, leading to development of endocrine abnormalities, insulin resistance, and DMT2 . DMT2 is a chronic, self-managed disease that significantly affects the lives of patients and their families. According to the biopsychosocial model originally proposed by Engel , the mind and body are two important systems that are interconnected. The model offers additional insights into how chronic illnesses such as diabetes can affect daily life. This model makes a distinction between pathological processes that cause disease, which includes the individual’s perception of his or her health and its subsequent impact on health. Stress and coping with diabetes can affect the severity of disease directly, through pathophysiological processes or indirectly, through patients’ own perception of illness by deteriorating adherence to therapy and daily functioning. The results of numerous studies indicated the presence of difficulties of many patients with diabetes living with their disease , such as the threat of serious complications (renal disease, amputation, blindness) and the potential for reduced life expectancy . The constant stress of maintaining tight glycemic control can result in two types of psychological distress: subclinical emotional distress and diagnosable psychological disorders .

Background/Aim. Antidepressants are a widely used class of drugs. The aim of this study was to investigate different aspects of antidepressant prescribing practice at University Psychiatric Clinic in Belgrade. Methods. This cross-sectional study was carried out by retrospective analysis of the patient's medical charts. The study included all patients with antidepressant prescribed at discharge during 2009 (n = 296). The evaluation was focused on patient- related factors (socio-demographic and illness related), psychiatrist-related factors (sex and duration of working experience) and drug related factors (type of antidepressant, dose, polypharmacy and reimbursement by national health insurance). Results. Antidepressants were prescribed for unipolar depression (F32-34, ICD X) either without comorbidity (46.2%) or with comorbidity (24.7%), mostly as a monotherapy (91% had one antidepressant), to the patients who were 65% female, aged 50.1 ± 8.9, most of them with 12 years of education (52.6%), married (69.3%) and employed (55.9%). The majority of patients had a history of two hospitalizations (Med 2; 25th-75th perc. 1-4) during nine years (Med 9; 25th-75th perc. 2-15) after the first episode of depression. Among them, 19% were found to be suicidal in a lifetime. The single most prescribed antidepressant was sertraline (20.4%), followed by fluoxetine (13.3%) and maprotiline (11.7%). Utilization of antidepressants was positively correlated with the rate of reimbursement (p < 0.01). The most prescribed antidepressant group was selective serotonin reuptake inhibitors (SSRI) (47.8%), followed by tricyclic antidepresants (TCA) (25.3%) and new antidepressants - venlafaxine, tianeptine, mirtazapine, bupropion, trazodone (15.1%). Most of the drugs were prescribed in doses which are at the lower end of the recommended dose-range. Regarding severity of the actual depressive episode, TCA were prescribed for severe depression with psychotic features, while SSRI were choice for episodes with moderate symptom severity (p = 0.01). Psychiatrists with longer working age (20-30 years) hesitated to prescribe new antidepressants in comparison to younger colleagues (p = 0.01). Conclusion. Economic issues in Serbia as developing country influence the choice of antidepressants, as well as a psychiatrist’s working age and severity of depression. However, SSRI are the drugs of the first choice, as it was shown in most of the developed countries nowadays.

Forensic psychiatry determination is, ordered by a court, the analysis and interpretation of medical facts with important legal implications. In that sense, psychiatrists (or neuropsychiatrists), apart from their professional expertise, must be familiar with legal, economical and social significance of medical data, so that their forensic reports are clear and useful in the context of legal procedure. This review deals with forensic psychiatry aspects of mental capacity. In the introduction of the article, the explanation of relevant concepts such as mental capacity, contractual and testamentary capacity, informed consent, undue influence and forensic determination in light of Serbian statutory law is presented. Further, the authors present basic principles of making forensic reports on mental capacity as well as contractual and testamentary capacity, and informed consent for eventual medical examination and treatment.

Introduction. The two types of stigmatization are social stigma, which includes discrimination, underestimation and distance in various social circumstances and personal stigma, which includes private relation i.e. a contact in person with stigmatized subject. Majority of recent publications has shown gender asymmetry in stigmatization (mostly indicating male predominance in stigmatizing processes), whereas the opposite data can be also found in some publications. The present study was aimed at exploring the relation of students' gender with their tendency to stigmatize subjects visiting a psychiatrist and at analyzing whether the gender influences the process of stigmatization. Material and methods. The survey included 523 students (227 on the second and 296 on the sixth year of School of Medicine, University of Belgrade). The instrument consisted of a vignette with questionnaire (14 items). Four versions of vignette were distributed: with/without 'label' and male/female subject in the vignette. Results. A more personal stigmatization was evident in the female students (p0.05). The stigmatization positively correlated with the intimacy of student's relation with the subject going to a psychiatrist. A higher rate of stigmatization was evident if the vignette was showing a person of the opposite gender. Discussion and conclusion. This is a unique study which analyzes separately the gender of a stigmatizing subject versus the subject being stigmatized and types of stigmatization. The data obtained should contribute to recognizing, understanding and controlling the widespread problem of stigma.

Epidemioloski podaci pokazuju da ce se broj osoba obolelih od dijabetesa skoro udvostruciti, sa 2,8% 2000. na 4,4%, 2030. Tada se može ocekivati porast ukupnog broja obolelih sa 171 milion, 2000. na 366 miliona ljudi u svetu 2030. Podaci posebno ukazuju na znacajno povecanje incidencije dijabetesa tip 2 (DMT2) . Dijabetes melitus je kompleksan metabolicki poremecaj u cijoj je osnovi deficit funkcije insulina i/ili produkcije insulina, koja je definisana kao nivo glikemije > 6,1 mmol/L. Etioloska klasifikacija dijabetesa od strane Svetske zdravstvene organizacije (SZO) prepoznaje vise tipova ove bolesti, od kojih su najcesci dijabetes tip 1 (autoimuna bolest koja dovodi do destrukcije beta celija pankreasa i gubitka produkcije i sekrecije insulina) i DMT2, kome pripada 85–90% bolesnika sa ovom bolesti. DMT2 najcesce se javlja posle 40. godine života, a najveca incidencija je oko 60. godine života. DMT2 je pracen funkcionalnom nesposobnoscu i smanjenjem kvaliteta života. Patogeneza DMT2 ukljucuje razlicite nivoe insulinske rezistencije, poremecaj funkcije beta celija pankreasa i deficit sekrecije insulina. DMT2 dovodi do disfunkcija multiplih organa ili tkiva, mikrovaskularnih (polineuropatija, retinopatija i nefropatija) i makrovaskularnih (kardiovaskularne bolesti) komplikacija. Istraživanja su pokazala da je DMT2 poligenski poremacaj, na ciji nastanak i ekspresiju znacajan doprinos imaju faktori sredine. Abdominalna gojaznost, povecanje indeksa telesne mase (odnos između telesne mase u kilogramima i visine tela u metrima na kvadrat) (ITM) i fizicka neaktivnost su najznacajnije determinante za razvoj DMT2. Kod oko 50% osoba, DMT2 ostaje neotkriven . Depresija je poremecaj koji je najzastupljeniji u psihijatrijskoj kazuistici. Prema procenama SZO 3 preko 120 miliona ljudi u svetu u svakom trenutku boluje od depresije i to skoro dvostruko vise žena nego muskaraca. Depresija je cetvrti vodeci uzrok funkcionalne nesposobnosti 90-ih godina proslog veka, a procenjuje se da ce do 2020. godine biti na drugom mestu, odmah posle kardiovaskularnih bolesti . Ovaj poremecaj se cesto javlja kao komorbidni i konkomitantni kod brojnih psihijatrijskih i somatskih bolesti, komplikujuci njihov tok i ishod. Depresija je pracena visokim rizikom od samoubistva, kao i povecanjem stope morbiditeta i mortaliteta. Životna prevalencija rekurentnog depresivnog poremecaja zavisi od pola i godina života, tako da u periodu od 30. do 44. godine, kada se najcesce javlja, njena incidencija iznosi oko 14 % kod žena i 7% kod muskaraca. Depresija je heterogeni poremecaj prema klinickoj fenomenologiji, ostaje cesto neprepoznata i nelecena. Nastaje kao rezultat međusobnih interakcija bioloskih, psiholoskih i socijalnih faktora (integralni model). Bioloski korelati depresije obuhvataju genetske, biohemijske, neurofizioloske, neuroimunoloske faktore, kao i neuroendokrinu disfunkciju. U etiopatogenezi depresije ucestvuju multipli neurotransmiterski sistemi (noradrenalin – NA, serotonin – 5-HT, dopamin – DA i drugi) .

Introduction Eating disorders indicate unhealthy habits in nutrition and/or behaviour in the feeding and maintaining of body weight. The main characteristic of these diseases is changed behaviour in nutrition, either as an intentional restriction of food, namely extreme dieting or overeating, i.e. binge eating. Extreme dieting, skipping meals, self-induced vomiting, excessive exercise, and misuse of laxatives and diuretics for the purpose of maintaining or reducing body weight are the forms of compensatory behaviour. Objective The purpose of the present research was to determine the presence of different inappropriate compensatory behaviours among eating disordered patients. Methods The experimental group included 35 female eating disordered patients of 23.02?}3.46 years on average, with anorexia or bulimia nervosa. The control group consisted of 70 girls aged 23.1?}3.0 years on average. Each participant completed a '24-hour Recall Questionnaire' and the 'Eating Disorder Diagnostic Scale'. Results A high statistically significant difference existed in the presence of all compensatory behaviours in the experimental and control group, regarding vomiting (?2=40.6; p

Introduction. This paper deals with medicolegal aspects of the hospital treatment of patients suffering from severe mental disorders and who are prone to violent behavior, dangerous to self and others. Violent acts in this study were defined as deliberate and nonconsensual acts of actual, attempted or threatened harm to a person or persons, and classified into categories of any type of violence, physical violence and nonphysical violence, which is in accordance with approaches used in other risk assessment researches. Outline of Cases. The authors present four cases of mentally ill inpatients whose violent behavior toward self or other persons resulted in self-destruction and physical aggression against other persons. The presented cases involved: 1) selfinjury in a patient with acute organic mental disorder after jumping through a hospital window, 2) suicide by drowning of a patient with acute mental disorder after escaping from intensive care unit, 3) suicide in a depressive patient after escaping from a low-security psychiatry unit, 4) physical violence against body and life of other persons in a patient with chronic mental disorder. Conclusion. The presented cases are considered to be rare in clinical practice and risk of violent behavior and the consequent danger of mentally ill inpatients may be efficiently predicted and prevented with appropriate hospital management based on 1) repeated escalation of violent behavior and 2) protection of the patient and others. Hence, if the physician, in order to prevent harmful consequences, does not apply all the necessary measures, including appropriate diagnostic and therapeutic procedures, as well as treatment in an adequate setting, such act is against the Criminal Law of the Republic of Serbia which sanctions physician's negligence. Also, according to the Law on Obligations of the Republic of Serbia this presents a legal ground for damage claim and the requirement of liability for nonmaterial damage within a civil procedure.

Drug utilization has been defined by the World Health Organization (WHO) as the „marketing, distribution, prescription and the use of drugs in a society, with a special emphasis on the resulting medical, social, and economic consequences“ . Drug utilization studies are usually aimed at drug use-related problem detection and quantification. These studies may be quantitative (with the objective to quantify drug usage at various levels of health-care system), or qualitative (L) (which assess the appropriateness of drug utilization) 2, . Utilization of psychiatric drugs is often a subject of drug utilization studies. Increasing researchers’ interest in prescribing and utilization of psychiatric drugs is noted worldwide . It is understandable, bearing in mind that these drugs are, maybe more than other pharmacotherapeutic groups, related to different epidemiologic, social and economic variables. It is usually a high rate of prescribing of certain psychiatric drugs, as well as selfmedication (e.g. with benzodiazepines) that causes concern, as well as the consequences of such practice: development of tolerance and addiction, drug abuse, and increased treatment costs. Over the last decade in Serbia several drug utilization studies on the usage of psychiatric drugs have been conducted. These studies have addressed certain major issues: drug use patterns, prescribing behavior, gaps between guidelines and actual utilization and factors responsible for polypharmacy. Both, quantitative and qualitative aspects of psychiatric drugs use have been analysed using up-to-date methodology. Such a modern methodological approach enables comparison of the data from Serbian studies with the data from other countries, thus pointing out certain prescribers’ habits and/or patients’ preferences that are characteristic for our milieu.

INTRODUCTION Schizophrenia patients are at greater risk of obesity, diabetes mellitus (DM), lipid abnormalities and cardiovascular disorders. The metabolic complications in patients are associated with several risk factors: family history of DM, lifestyle, smoking, dietary habits, physical inactivity, but also with antipsychotic medication. In literature, most publications have been focused on the effects of the second generation antipsychotics (SGA) on glucose metabolism. However, less attention has been paid to abnormality in glucoregulation, patients with schizophrenia treated with the first generation antipsychotics (FGA). OBJECTIVE The present study evaluated glucose metabolism in normal weight schizophrenia patients treated with FGA. METHOD The cross-sectional study included 18 patients (FGA treated) and 20 healthy controls with neither group differences in sex distribution, age, nor in BMI. Inclusion criteria were normal BMI (20-25 kg/m2). The glucose levels, insulin levels and growth hormone levels during oral glucose tolerance test (OGTT) were measured. RESULTS Fasting glucose and insulin levels did not differ significantly between groups. Groups differed in OGTT glucose and insulin peak and area under curve (AUC), level of significance p < 0.05 (patients vs. controls: glucose peak 8.3 +/- 0.4 vs. 6.9 +/- 0.5 mmol/l, glucose AUC 758 +/- 28 vs. 640 +/- 36 mU/l/120 min; insulin peak in patients 92.7 +/- 15.6 mU/l; insulin AUC 6060 +/- 1016 mU/l/120 min, insulin peak in controls 47.9 +/- 6.5 mU/l; insulin AUC 2597 +/- 256 mU/l/120 min). CONCLUSION Patients with schizophrenia, although with normal body mass index, are at high risk of abnormal glucose regulation. Not only SGA increase the risk of impaired glucoregulation and metabolic syndrome, but this may also be due to FGA or schizophrenia per se.

INTRODUCTION Parricide is defined as a murder of parents by their children; the patricide is murder of father, while matricide is murder of mother. This entity is classified as homicide, but it differs in the fact that victims are parents and the killers are their children. Mostly, it is associated with psychiatric morbidity. OBJECTIVE To describe sociodemographic and psychopathological characteristics of parricide committers and to analyze circumstances of parricide and psychiatric morbidity in order to achieve better recognition and prevention of risks. METHOD This retrospective study included all homicide autopsy records (1991-2005) performed at the Institute of Forensic Medicine, Medical School, University of Belgrade. For further analyses, all parricide records were selected out. The study analyzed all available parameters, which concerned parricide committers, victims and the act itself. Methods of descriptive statistics were used. RESULTS Between 1991 and 2005, there were 948 cases of homicide; of these, 3.5% were parricides. The committers of parricide were on average 31.2?11.9 years old, 87.8% were males, 60.6% with psychiatric symptoms most commonly with schizophrenia, alcohol dependence, personality disorder etc. Victims were on average 63.7?11.9 years old, 54.5% males, and 21.2% had a diagnosed mental illness. CONCLUSION Parricide is a rare kind of homicide accounting for 3% of all homicides. Committers are mostly unemployed males in early adulthood who have mental disorder. The phenomenon of parricide deserves a detailed analysis of the committer (individual bio-psycho-social profile) and the environ- mental factors (family, closely related circumstances) to enable a precise prediction of the act and prevention of the fatal outcome, which logically imposes the need of further studies.

Context: Atypical antipsychotics (SGA) have the propensity to induce weight gain. Objective: The aim was to evaluateearly changes in hormones involved in neuroendocrine regulations (serum cortisol, growth hormone and prolactin) and positive energy balance (serum insulin, leptin and ghrelin) during SGA treatment in normal-weight patients with schizophrenia with the purpose of exploring the possibility to combat weight gain early through manipulation of circulating hormone levels. Design: We conducted a randomized, partly cross-sectional and partly longitudinal, prospective study. Setting and Patients: Eighteen normal-weight in-patients with schizophrenia treated with FGA (first-generation antipsychotics) were referred to the Institute of Psychiatry. Twenty age-, gender- and BMI-matched healthy subjects were investigated at the Neuroendocrine Unit, Belgrade University. Intervention: Oral glucose tolerance test (OGTT) was performed at baseline in all and then 13 patients were assigned to receive SGA (risperidone or clozapine) and OGTT was repeated after 1 and 3 months. Results: At baseline, patients with schizophrenia had higher peak glucose levels (p < 0.05), glucose area under the curve (AUC; p < 0.05), peak insulin levels (p < 0.05), insulin AUC values during OGTT (p < 0.01) and the calculated homeostasis model assessment (HOMA-IR) value than control subjects (p < 0.05). Patients with schizophrenia showed higher morning cortisol (p < 0.05) levels than control subjects. After 1 and 3 months of SGA therapy patients with schizophrenia gained bodyweight by 3.5 and 8.6%, respectively. Leptin levels steadily increased while cortisol levels decreased in the first month and remained so. Serum glucose, insulin and ghrelin levels on SGA were similar as at baseline. Circulating ghrelin levels decreased after OGTT during SGA which is consistent with a role for ghrelin in the initiation of meals. Conclusions: Treatment with SGA was associated with continuous weight gain, with an early increase in serum leptin levels and decrease in cortisol levels. Elevated circulating leptin was ineffective in the control of fat deposition. Similar plasma ghrelin levels and similar decrease pattern of ghrelin after OGTT compared to healthy subjects signify intact meal-promoting effects of ghrelin during SGA therapy, which at the same time renders anorexigenic pathways ineffective. This may lead to weight gain and further studies with a ghrelin antagonist may provide support for this hypothesis.

The organizational structural effects of estrogen may be cumulative and permanent by impacting on neurodevelopment, giving rise to “neuroprotective” effects and eventually reduction of psychosis risk. Reduction in bone mineral density (BMD, in g/cm 2 ), as a biological marker of reduced cumulative exposure to estrogen, may be a marker of increased psychosis risk. A sample of 19 first-episode female psychosis patients with minimal previous antipsychotic exposure (mean 10 weeks) and 20 female controls underwent advanced fan-beam dual X-ray absorptiometry (DXA) to assess lumbal spine BMD of the region of L1–L4. Mean BMD was around one standard deviation lower in patients (1.13, S.D.=0.10) than in controls (1.25, S.D.=0.12; p =0.0021), and 84% of patients scored below the median value of the controls (OR=5.3, 95% CI: 1.2, 24.2). The results are compatible with the hypothesis that psychosis in women may be associated causally with a reduced protective effect of estrogen over the course of development.

Recent studies have demonstrated that hypopituitarism, in particular GH deficiency, is common among survivors of traumatic brain injury (TBI) tested several months or yr following head trauma. We present the results of endocrine, neurological, neuropsychological and psychiatric evaluation in a group of 67 patients who suffered TBI at least one yr ago. Our study shows that decreased endocrine function is either restricted to one or more anterior pituitary hormones and is present in 34% of patients with any pituitary hormone deficit, while multiple pituitary hormone deficiencies are found in 10% of patients. GH/IGF-I axis was evaluated by GHRH+GHRP-6 test and IGF-I measurement. Severe GHD is the most frequent deficiency present in 15% of TBI patients. Gonadotrophin deficiency was present in 9% of patients with TBI, while thyrotroph and corticotroph function seemed more refractory to impairment. Patients with moderate-to-severe trauma are not necessarily more likely to have hypopituitarism than those with mild injury. Neuropsychological testing revealed a significant positive correlation of peak GH levels after GHRH+GHJRP-6 test with verbal learning and verbal short term memory (RAVLT total score p = 0.06, immediate free recall p = 0.02 and delayed free recall p = 0.04). Verbal and visual memory was significantly lower in elderly patients and in males. Visoconstructional abilities (RCF copy) were significantly lower in the elderly (p0.01) and undereducated (p = 0.02). Visual memory (free recall of complex figure after 30 min) significantly correlated with lower IGF-I levels (p = 0.01). Gonadotrophins and testosterone correlated significantly with visoconstructional abilities. Simple and complex conceptual tracking (TMT A and B) was significantly more impaired in older TBI patients (p0.01) and with longer time from trauma (TMT B only, p = 0.03). The psychiatric evaluation by using two different scales showed depression, phobic anxiety and psychoticism to be more prominent in the TBI group. Paranoid ideation and somatization negatively correlated with the peak GH responses to GHRH+GHRP-6 test (p = 0.04 and p = 0.03, respectively). Depression scale showed that nearly half of patients suffered from mild to moderate depression. The benefits of hormone replacement therapy on cognitive functioning and mental distress in TBI patients are eagerly awaited.

IntroductionTreatment with pegylated interferon alpha (PEG-IFN-α) in patients with chronic hepatitis C (CHC) is associated with depressive symptomatology more frequently than other inflammatory diseases treated with PEG-IFN-α.ObjectivesTo prospectively evaluate the onset, course and resolution of depressive symptomatology in CHC patients treated with PEG-IFN-α.MethodsHamilton depression rating scale (HAMD) was used to asses depressive symptoms in 103 subjects with CHC prior to initiation of PEG-IFN-α (mean dose 152.6 ± 25.6 mcg; duration of therapy 48 weeks) and at the follow-up visits (4th, 12th, 24th, 48th and 72th week). Control group consisted of 103 CHC subjects, without PEG-IFN-α.ResultsOur results showed a significant increase in HAMD scores as early as in the 4th week of PEG-IFN-a therapy compared to HAMD scores prior to initiation of PEG-IFN-α (38.8% vs. 24.3%). The peak of depressive symptomatology was evidenced in the 12th week (mean HAMD 9.34 ± 6.93), when almost 50% of patients had HAMD above 7. At the end of the treatment (48th week), 38.8% had HAMD above 7, and in the 72nd week (24 weeks after the therapy completion) prevalence of depression was decreased to the values lower than at baseline (23.3% vs. 24.3%). No change in prevalence of depression was detected in control group.ConclusionOur results are important because they show the overall course of depressive symptomatology during the interferon therapy. These data also show spontaneously resolution of depression 6 months after the completion of PEG-IFN-α. This study is the longest study in this area.Disclosure of interestThe authors have not supplied their declaration of competing interest.

Ksenija Atanasijević (1894-1981) was the first woman in Serbia to obtain a Ph. D. in philosophy. Going through numerous psychological metamorphoses in her lifetime and confronted with numerous challenges, Ksenija Atanasijević developed a specific philosophical-psychological system of consolation prominently featuring the concepts of happiness, bliss, moderation, courage and wisdom. Modifying the original teachings of Democritus and Epicurus, Ksenija Atanasijević developed a distinctive anthropology based on confrontation with but equally the overcoming of obstacles, both internal (spiritual) as well as external ones. The philosopheress developed a reflexive and indeed metaphysical defensive psychotherapeutical skill at the root of which was cleansing the soul, as well as dedication to the realm of fancy, fantasy and imagination. Ksenija Atanasijević also had precious literary talent which was best expressed in her analyses of the poetry and prose of great Serbian writers (Pandurović, Njegoš, Nastasijević, etc.). It is quite certain that this, with Anica Savić-Rebac, definitely greatest Serbian philosopheress, through personal suffering, creative solitude and shrouded desperation built an utterly authentic and harmonious system of philosophical comfort.

The aim of this study was to investigate the influence of certain psychosocial factors - insight, psycho-education, family and social support, loneliness and social isolation - on the appearance of depression and suicidal risk in schizophrenia.This was a cross-sectional study that comprised hospitalized patients with schizophrenia in the initial remission phase. The assessment of depression and suicidal risk was made by applying a semi-structured psychiatric interview that included scrutinized factors (insight, psycho-education, family and social support, loneliness and social isolation), Positive and Negative Syndrome Scale (PANSS), and Calgary Depression Scale for Schizophrenia (CDSS). On the basis of the assessment results, the sample was divided into two groups: Group of patients with depression and suicidal risk in schizophrenia (N = 53) and Control group (N = 159) of patients with schizophrenia without depression and suicidal risk.In the Group of patients with depression and suicidal risk, compared with the Control group, there was significantly higher frequency of insight in the mental status (χ² = 31.736, p0.001), number of patients without psycho-education (χ² = 10.039, p = 0.002), deficit of family support (χ² = 13.359, p = 0.001), deficit of social support (χ² = 6.103, p=0.047), loneliness (χ² = 6.239, p = 0.012), and social isolation (χ² = 47.218, p0.001). Using the model of multi-variant logistic regression, insight, deficit of psycho-education and social isolation (p0.05) were identified as predictors of depression and suicidal risk in schizophrenia.This study shows that considered psycho-social factors - insight in the mental status, lack of psycho-education, as well as social isolation - could be predictors for appearance of depression and suicidal risk in schizophrenia.

The aim of this study was to define all the areas of changes in expression of nuclear c-Fos protein (c-Fos), cytoplasmic somatostatin (SS) and neuropeptide Y (NPY) in rat brain during experimental ischemia. Using the immunohistoche- mical method, brain mapping (based on the atlas by Paxinos & Watson) of immunoreactivity for c-Fos, SS and NPY in 39 rats, was studied in telencephalon, diencephalon and midbrain after resistant and transitory ischemia. The first ex- perimental group (R group) was exposed to resistant ischemia by occlusion (10 minutes) of four vessels according to the Pulsinelli method. The second group was first exposed to transitory (4 minutes) ischemia (preconditioning) and, after 72 hours, to total ischemia as in the R group. There was a statistical difference between the R and T group in the c-Fos reac- tion, especially in the parietofrontal cortex, anterior amygdaloid area, claustrum, reuniens nucleus and suprachiasmatic nucleus. The dominant immunohistochemical reactivity was found for c-Fos protein, and the most reactive in terms of co-localization of c-Fos with SS and NPY was periventricular area of hypothalamus. The mapping showed that both, phylogenetically new as well as phylogenetically older brain structures reacted immunohistochemically. The results of our study, regarding the impact of preconditioning with a short period of ischemia on c-Fos activity and co-localization of c-Fos with SS and NPY immunoreactivity, showed the need for future studies of brain neuropeptides related to re- gional and time effects, and indicated brain structures which may require pharmacological targeting to achieve neuro- protective level of proto-oncogene activity in populations at risk.

Background: Depression can be a sequela of a medical condition like traumatic brain injury (TBI), but the relationship between brain trauma and depression has not been recognized until recently. Eight to 15% of adults who sustain a TBI have severe and isolated growth hormone deficiency (GHD). It has been shown that GHD in adults is associated with changes in body composition, impairment of quality of life, and depression. Methods and Results: At the time of evaluation, two adult subjects who suffered TBI several years ago presented with isolated GHD together with depression. Prior to trauma, neither subject had psychiatric or endocrine morbidity. These case reports focus on opportunities and difficulties in deciding how best to treat them. Conclusions: Both depression and TBI are highly ranked in the list of burden of disease. The mechanism of depression in GH-deficient adults who have sustained a TBI should be clarified and the efficacy and tolerability of GH replacement therapy versus placebo versus antidepressant drugs should be assessed.

The mechanism of maladaptive chronic stress response involves altered phosphorylation of the glucocorticoid receptor (GR). In this study, we investigated if important depressogenic vulnerability factors, such as neuroticism and self-reports of negative affective states, may be associated with alterations in levels of the GR and GR phosphoisoforms in peripheral blood mononuclear cells (PBMC) of healthy adults. In 21 women and 16 men we evaluated PMBC levels of total GR (tGR), GR phosphorylated at serine 211 (pGR-S211) and serine 226 (pGR-S226) and correlated these data with personality traits and current reports of stress, anxiety and depression. Also, we assessed plasma cortisol levels in all tested subjects. Our results showed that in women nuclear pGR-S226 was positively correlated with neuroticism and current reports of depression, anxiety and stress, while the ratio of nuclear pGR-S211/pGR-S226 was negatively correlated with reports of depression. None of the aforementioned correlations were significant in men. No significant relations between cortisol levels and any of GR parameters were observed. These preliminary findings highlight the value of GR phosphorylation-related research in identifying molecular biomarkers of depressogenic vulnerability, at least in women. (C) 2013 Elsevier Ireland Ltd. All rights reserved.

IntroductionTreatment with pegylated interferon alpha (PEG-IFN-α) is associated with depression more frequently in chronic hepatitis C (CHC) patients than with other inflammatory diseases.ObjectivesTo prospectively asses sex differences in the prevalence of depression in CHC patients during the PEG-IFN-α, as well as in the CHC group with no therapy.MethodsSample consisted of 103 subjects with CHC on the PEG-IFN-α and 103 subjects with CHC without interferon therapy. The diagnosis of depressive disorder was established by using Structured Clinical Interview and Criteria of International Classification Disorder. The severity of depression was assessed by using Hamilton Depression Rating Scale (HAMD ≥ 8) prior to PEG-IFN-α (baseline) and at the follow-up visits (4th, 12th, 24th, 48th, 72nd week).ResultsDuring the course of PEG-IFN-α, 49.5% of subjects showed depressive symptomatology (HAMD ≥ 8). Except at baseline and in the 72nd week, on the all other follow-up visits the prevalence of depression was significantly higher in female subjects (*all Ps < 0.05). The strongest difference was observed in the 12th week: of all the subjects with HAMD ≥ 8, 68.8% were female and 32.7% were male (P < 0.001). The multivariate logistic regression model showed that female sex is a very strong predictor for the development of depression during the interferon treatment [Exp (B) = 6.729]. There were no significant sex differences in the prevalence of depression in the control group.ConclusionsOur study (the longest study in this area) indicate that the prevalence of depression is significantly higher in female subjects with CHC during antiviral treatment.Disclosure of interestThe authors have not supplied their declaration of competing interest.

More than half a century ago, Delay and colleagues have discovered, quite accidentally, that antihistamine (chlorpromazine) relieves psychotic symptoms. This discovery prompted further investigation through a series of performed experiments aimed to elucidate the antipsychotic mechanism of action. Initial results have shown that antipsychotic drugs in experimental animals lead to "neuroleptic effect" (indifference). However, not until the end of 1960s, it becomes clear that all previously known antipsychotics block dopamine receptors, particularly postsynaptic D2 receptors. The next three decades marked the development and application of these so-called classic neuroleptics in the treatment of psychotic patients. During the nineteen nineties, as a result of ongoing efforts to achieve greater efficiency and reduce the scope of side effects, novel antipsychotics were synthesized (second generation antipsychotics--SGA). As a result the notion of serotonin-dopamine antagonist (SDA) was formulated. According to one of the hypothesis, "new", so called atypical antipsychotic drugs strongly block the serotonin (5-HT2), and weakly block the dopamine (D2) receptors. Yet, there is still a debate as to the molecular basis of atypicality, whether it is in dopaminergic and serotonergic antagonism of neurotransmission or it lays exclusively in the modulation of dopaminergic system and dissociation rate at the level of D2 receptors in specific brain regions. Although the synthesis and use of antipsychotics in clinical practice have radically changed not only the basic approach to the patient, but also the quality of life of millions of people, the question remains whether this is just "old wine in new glasses".

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.

Background: Anxiety may occur as ictal, postictal or interictal symptom in patients with epilepsy. The main aim of this research was to explore the intensity and frequency of anxiety in patients with generalized, temporal and extratemporal epilepsy. Subjects and methods: This is a cross-sectional study of three groups of patients with epilepsy (30 patients per group) - recently diagnosed with generalized epilepsy, temporal epilepsy and extratemporal epilepsy, and a healthy control group (N=30). The Beck Anxiety Inventory (BAI) was used for quantitative assessment of anxiety. Results: Patients with temporal and extratemporal epilepsies had a significantly higher mean total scores on the BAI than the patients with generalized forms of epilepsies (ANOVA: F=6.323, p0.05). For the first three symptoms - numbness, wobbling in the legs and the fear of the worst happening - the group of patients with extratemporal epilepsies had significantly higher average levels of intensity and frequency of symptoms (ANOVA: F1=5.591, F2= 6.555, F3=5.906; p

Backround: Stigmatization of psychiatric patients is present both in the general population and among healthcare professionals. Aim: To determine the attitudes and behaviour of medical students towards a person who goes to a psychiatrist, before and after psychiatric rotation, and to compare those attitudes between medical and non-medical students. Methods: The study included 525 medical students (second and sixth year of studies) and 154 students of law. The study instrument was a three-part self-reported questionnaire (socio-demographic data, Rosenberg Self-Esteem Scale and a vignette depicting a young, mentally healthy person). The experimental intervention consisted of ascribing a ‘psychiatric label’ to only one set of vignettes. All the vignettes (with or without the ‘psychiatric label’) were followed by 14 statements addressing the acceptance of a person described by vignette, as judged by social distance (four-point Likert scale). Results: Higher tendency to stigmatize was found in medical students in the final year, after psychiatric rotation ( Z U = −3.12, p = .002), particularly in a closer relationship ( Z U = −2.67, p = .007) between a student and a hypothetical person who goes to a psychiatrist. The non-medical students had a similar tendency to stigmatize as medical students before psychiatric rotation ( Z U = −0.03, p = .975). Neither gender, nor the size of student’s place of origin or average academic mark was associated with the tendency to stigmatize in our sample. However, student’s elf-esteem was lower in those with a tendency to stigmatize more in a distant relationship (ρ = −0.157, p = .005). Conclusions: Psychiatric education can either reinforce stigmatization or reduce it. Therefore, detailed analyses of educational domains that reinforce stigma will be the starting point for anti-stigma action.

Background: Type 2 diabetes (T2DM) doubles the odds of comorbid depression. Depression is a strong predictor of developing T2DM. The aim of the study was to compare depressed patients with T2DM to non-depressed ones with respect to demographic, psycho-social, clinical, anthropometric and metabolic characteristics; to examine the relationship between glycemic control and depression severity in depressed patients; to estimate the risk factors of depression. Subjects and Methods: A group of depressed diabetic patients comprising those with a Major depressive episode, first or repeated (ICD-10; 1992) and endocrinologist-diagnosed T2DM, duration ≥5 years on oral, insulin therapy or both (N=46) and nondepressed ones (N=44) (90 in total) of both genders (

Background: The disorder of biogenic amine metabolism (serotonin – 5-HT and dopamine – DA) is expected in the brain (neuron) damage caused by acute ischemia. It is known that long-term abuse of ethyl-alcohol damages the quality of neurons diffusely in the brain. Cerebrospinal fluid (CSF) and its biochemical content, 5-HT and DA, are reliable indicators of the vitality of neurons. The main objective of this research was to demonstrate that the elevated content of metabolites 5-HT and DA in the CSF in patients with acute brain infarction, who were pre-morbid alcohol-dependent patients, is additionally emphasized by diffusive damage of neuron vitality caused by alcoholism. Subjects and methods: Study sample consists of two groups - 50 alcohol-dependent patients with acute brain infarction under the age of 65 (group A) and 50 patients with acute brain infarction who were not alcohol-dependent (group B). All subjects underwent the same procedure - CSF was taken during admission to the hospital and history was obtained through anamnesis, heteroanamnesis and clinical examinations. Results: Metabolism of DA and metabolic turnover of DA (3, 4 dihydroxyphenylacetic acid + homovanilic acid; DOPAC + HVA) was elevated in the liquor of both patient groups. The statistically significant difference between the groups was found in metabolic turnover of 5-HT (p

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.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.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.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.

A hundred years after psychoanalysis was introduced, neuroscience has taken a giant step forward. It seems nowadays that effects of psychotherapy could be monitored and measured by state-of-the art brain imaging techniques. Today, the psychotherapy is considered as a strategic and purposeful environmental influence intended to enhance learning. Since gene expression is regulated by environmental influences throughout life and these processes create brain architecture and influence the strength of synaptic connections, psychotherapy (as a kind of learning) should be explored in the context of aforementioned paradigm. In other words, when placing a client on the couch, therapist actually placed client's neuronal network; while listening and talking, expressing and analyzing, experiencing transference and counter transference, therapist tends to stabilize synaptic connections and influence dendritic growth by regulating gene-transcriptional activity. Therefore, we strongly believe that, in the near future, an increasing knowledge on cellular and molecular interactions and mechanisms of action of different psycho- and pharmaco-therapeutic procedures will enable us to tailor a sophisticated therapeutic approach toward a person, by combining major therapeutic strategies in psychiatry on the basis of rational goals and evidence-based therapeutic expectations.

During the 3-month bombing of Serbia (March 24–June 9, 1999), the entire population, including pregnant females as an especially vulnerable group, was exposed to a high degree of stress. This is the first study to explore the effects of prenatal stress during the 1999 bombing of Belgrade on the main obstetric characteristics of newborns. The design of the study was retrospective cross-sectional. The total number of birth records in the sample was 3,815, namely, 1,198 from the group exposed to prenatal stress and 1,251 and 1,366 from the respective control periods, years 1996 and 2003, when no stressful events affected the city. We found that exposed mothers gave birth to infants with statistically significantly lower birth weight (BW; mean difference = 86 g, 95% confidence interval = 67 to 104; F (1, 3,349) = 80.8, p

INTRODUCTION Currently available evidence reveals comparatively few studies of psychological effects of hearing impairments, in spite of the fact that clinicians have for a long time been aware of a connection between the acquired hearing impairment and mental disorders. They are focused on the investigation of dysfunction in general. Thus, three domains of the auditory imbalance may be distinguished: disorder, disability and handicap. 'Handicap', according to the definition of the World Health Organization, is a hindrance in an individual that results from an impairment or disability and represents psychological response of the individual to the impairment. OBJECTIVE Validation of acquired hearing impairment as a risk factor of psychical disorders as well as an analysis of relation of some demographic factors (sex, age, education) and audiological factors (degree and duration of the impairment) with the frequency of hearing handicap. METHOD MMPI-201 has been applied in 60 subjects affected with otosclerosis, potential candidates for stapedectomy, before and after the surgery. RESULTS Individuals with acquired hearing impairment manifest more frequent disorders of psychical functioning in comparison with general population, while demographic and audiometric parameters did not correlate with acquired hearing handicap. CONCLUSION It may be assumed that the very recognition of demographic and audio-logical factors can not help much in the understanding of the psychological stress associated with hearing impairment.