The Risk Model of Developing Schizophrenia Based on Temperament and Character.

INTRODUCTION: Cloninger's psychological model of temperament and character confirms that the personality development is influenced by biological and psychological processes. The aim of this study is to examine personality dimensions and to determine which variable separates the healthy from the ill in the best way and could be a possible psychological marker for the presence of the illness. METHODS: This research included 152 subjects, 76 patients with schizophrenia and 76 healthy controls, selected on the basis of medical interviews, random population sampling model from a wider social community using the independent T-Tests. The Temperament and Character Inventory (TCI), which compared personality traits of the patients with schizophrenia and the healthy control group, was used. Dependence of variables in these categories was assessed using the Chi-square and Fisher's tests, and the impact of variables on schizophrenia was tested using univariate and multivariate binary logistic regression. The same method was used for making the mathematical model. RESULTS: Unlike the control group, patients with schizophrenia exhibited higher Harm avoidance (HA) and Self - transcendence (ST) scores as well as lower Self - directedness (SD) and Cooperativeness (C) scores. Multivariate binary logistic regression showed that Responsibility, Purposefulness, Resourcefulness, Cooperativeness and Compassion dimensions were significantly more present in the patients with schizophrenia. The new variable Model (area=0.896, p<0.0005) is composed of five TCI parameters. It proved to be a reliable marker for separation the healthy from the ill ones (area=0.896, p<0.0005). It has a good sensitivity (80%) and specificity (84%). CONCLUSIONS: Research has emphasized variables in the temperament and character inventory, which are the best markers for distinguishing between the healthy and the ill, thus making the mathematical model.

Parameters of Calcium Metabolism Fluctuated during Initiation or Changing of Antipsychotic Drugs.

OBJECTIVE: Serum parameters of calcium homeostasis were measured based on previously published evidence linking osteoporotic fractures and/or bone/mineral loss with antipsychotics. METHODS: Prospective, four-week, time-series trial was conducted and study population consisted of patients of both genders, aged 35-85 years, admitted within the routine practice, with acute psychotic symptoms, to whom an antipsychotic drug was either introduced or substituted. Serial measurements of serum calcium, phosphorous, magnesium, 25(OH)D, parathyroid hormone, calcitonin, osteocalcin and C-telopeptide were made from patient venous blood samples. RESULTS: Calcium serum concentrations significantly decreased from baseline to the fourth week (2.42±0.12 vs. 2.33±0.16 mmol/L, p=0.022, n=25). The mean of all calcemia changes from the baseline was -2.6±5.7% (-24.1 to 7.7) with more decreases than increases (78 vs. 49, p=0.010) and more patents having negative sum of calcemia changes from baseline (n=28) than positive ones (n=10) (p=0.004). There were simultaneous falls of calcium and magnesium from baseline (63/15 vs. 23/26, p<0.001; OR=4.75, 95% CI 2.14-10.51), phosphorous (45/33 vs. 9/40, p<0.001; 6.06, 2.59-14.20) and 25(OH)D concentrations (57/21 vs. 13/35, p<0.001; 7.31, 3.25-16.42), respectively. Calcemia positively correlated with magnesemia, phosphatemia and 25(OH)D values. Parathyroid hormone and C-telopeptide showed only subtle oscillations of their absolute concentrations or changes from baseline; calcitonin and osteocalcin did not change. Adjustment of final calcemia trend (depletion/accumulation) for relevant risk factors, generally, did not change the results. CONCLUSION: In patients with psychotic disorders and several risks for bone metabolism disturbances antipsychotic treatment was associated with the decrease of calcemia and changes in levels of the associated ions.

CONTEMPORARY PRINCIPLES OF SUICIDE PREVENTION.

INTRODUCTION: Suicide remains a significant public health problem worldwide. This study is aimed at analyzing and presenting contemporary methods in suicide prevention in the world as well as at identifying specific risk groups and risk factors in order to explain their importance. in suicide prevention. MATERIAL AND METHODS: The literature search covered electronic databases PubMed, Web of Science and Scopus. In order to select the relevant articles, the authors searched for the combination of key-words which included the following medical subject heading terms (suicide or suicide ideation or attempted) and (prevention or risk factors) and (man or elders or mental disorders). Data analysis covered meta-analyses, systematic reviews and original scientific papers with different characteristics of suicide preventions, risk factors and risk groups. RESULTS: Worldwide evidence-based interventions for suicide prevention are divided in universal, selective and indicated interventions. Restricted approach to various methods of committing suicide as well as pharmacotherapy contributes to a lower suicide rate. Suicide risk factors can be categorized as proximal and distal. The following groups are at highest risk of committing suicide: males. older persons and persons with registered psychiatric disorders. CONCLUSION: There is a lot of evidence that suicide is preventable. It is known that only 28 coun tries in the world have national suicide prevention strategies and Serbia is not one of them.

Long-Term Treatment with Olanzapine in Hospital Conditions: Prevalence and Predictors of the Metabolic Syndrome.

INTRODUCTION: The risk of metabolic abnormalities is greatly increased in schizophrenic patients started on an atypical antipsychotic medication. Patients with psychiatric disorders exceed mortality ranges resulting from, among others, increased risk of cardiovascular events. Other factors contributing to the development of metabolic syndrome include prolonged duration of illness, increasing age, female sex and lifestyle factors. OBJECTIVE This cross-sectional study was taken up to assess the prevalence of the metabolic syndrome (MetS) in schizophrenic patients receiving olanzapine monotherapy for at least six months and to determine the most important risk factors associated with metabolic syndrome presence in these patients. METHODS A total of 93 long term hospitalized schizophrenic patients (71 men, 22 women), had a screening of the following: case-history data, psychiatric scales, anthropometric measures, blood (fasting glucose, lipid status, C-reactive protein--CRP) and urine samples (microalbuminuria). RESULTS: Prevalence of MetS according to International Diabetes Federation criteria in our study was 34.4%. The multivariate analysis distinguished the following significant predictors of MetS presence (in order of appearance): data about diabetes mellitus in family history (p = 0.002), body mass index > 25 kg/m2 (p = 0.002), hyperlipidemia in family history (p = 0.008), and elevated CRP value (p = 0.042). CONCLUSION: High rate of MetS in patients treated with olanzapine in this study exceeds MetS prevalence in general population. Among observed parameters, our study pointed to several "high risk" predictors associated with MetS presence. Regular monitoring of cardiometabolic risk factors is highly recommended. Positive heredity distress mentioned above may direct a psychiatrist to prescribe some other drug than olanzapine in the long term treatment of schizophrenia.

Metabolic syndrome and C-reactive protein in patients with depressive disorder on antidepressive medication.

INTRODUCTION: Recurrent depression is a psychiatric disorder of which etiology and pathogenesis might be related to immune response. Metabolic Syndrome (MetS) and its components are also strongly associated with elevated inflammatory indicators, as so as the body mass index (BMI) and total cholesterol levels. OBJECTIVE: Objective of this study was to investigate if there was any difference in C-reactive protein (CRP) levels in patients with recurrent depressive disorder, treated with antidepressants, compared to a healthy control group of subjects and if there was an association between increased CRP levels and the presence of MetS in these two groups. METHODS: Sixty subjects entered the study; of these 35 patients with the diagnosis of recurrent depressive disorder, while the healthy control group included 25 subjects. MetS was defined according to the NCEP ATP III criteria. The cut-off point for CRP was set at > 5 mg/L. RESULTS: There was no statistically significant difference in the prevalence of MetS and CRP values between the studied groups. Waist circumference and total cholesterol levels were significantly higher in the experimental group. Patients that fulfilled the criteria for MetS showed significantly higher values of central obesity and arterial hypertension in the experimental group as well. The elevated CRP levels were associated with increased frequency of MetS in depressed patients. CONCLUSION: Both CRP levels and metabolic risk profile screening, according to the international criteria, may be beneficial in order to obtain better assessment for depressive long-term medicated patients.

[Brain tumors in patients primarly treated psychiatrically].

INTRODUCTION: Psychiatric symptoms are not rare manifestations of brain tumors. Brain tumors presented by symptoms of raised intracranial pressure, focal neurological signs, or convulsions are usually first seen by the neurologist or less frequently by the neurosurgeon in routine diagnostic procedures. On the other hand, when psychiatric symptoms are the first manifestation in "neurologically silent" brain tumors, the patients are sent to the psychiatrist for the treatment of psychiatric symptoms and brain tumors are left misdiagnosed for a long period of time. CASE REPORT: We presented three patients with the diagnosed brain tumor where psychiatrist had been the first specialist to be consulted. In all three cases neurological examination was generally unremarkable with no focal signs or features of raised intracranial pressure. CT scan demonstrated right insular tumor in a female patient with obsessive-compulsive disorder (OCD); right parietal temporal tumor in a patient with delusions and depression and left frontal tumor in a patient with history of alcohol dependency. CONCLUSION: Psychiatric symptoms/disorders in patients with brain tumors are not specific enough and can have the same clinical presentation as the genuine psychiatric disorder. Therefore, we emphasize the consideration of neuroimaging in patients with abrupt beginning of psychiatric symptoms, in those with a change in mental status, or when headaches suddenly appear or in cases of treatment resistant psychiatric disorders regardless the lack of neurological symptoms.

First generation antipsychotics switch with Risperidone in the treatment of chronic schizophrenic patients.

BACKGROUND: Schizophrenia is a severe chronic psychiatric disorder for which treatment compliance is important in the prevention of relapse. Second generation antipsychotics (SGA), such as Risperidone, have been found to be more effective in the treatment of such patients than the high potency first generation antipsychotics (FGA). This is an open study where the same group of patients was first treated with FGA and then were switched to Risperidone, in controlled hospital conditions, after a wash- out period. The aim of the study was to examine whether patients with schizophrenia who were judged to be stable on long-term treatment with FGA would further benefit from a switch to an atypical antipsychotic drug. SUBJECTS AND METHODS: Eighty hospitalized patients suffering from Schizophrenia or Schizoaffective disorder (male 54, female 26) were first treated with Haloperidol (N=60) or Fluphenazine (N=20), and then were switched to Risperidone. Their clinical state was monitored using the PANSS scale for Schizophrenia, measuring the Total PANSS score. The KLAWANS scale for assessment of extrapyramidal syndrome (EPS) was also used. Administration and dosage of Trihexiphenidil (THF) was recorded. The study lasted for 8 weeks, with 4 screenings (Visit 0-baseline- FGA, Visits 1-3 Risperidone on Day 14, 28 and 56, respectively). RESULTS: The average age was 38. Patients usually suffered the paranoid form of Schizophrenia (55%). The duration of illness was more than 5 years (38.8%). During the eight- week trial on Risperidone, using the PANSS total scores, we observed clinical improvement where the therapy switch had caused an initial worsening (p<0.05). Also, the compared baseline (FGA) and last visit showed a low, but statistically significant benefit in favor of Risperidone (t=5.45, df=79, p<0.005). Intensity of EPS measured by KLAWANS scores significantly decreased during time (F=4.115; p=0.016; Partial Eta Square=0.058). Average Trihexiphenidil doses followed Risperidone in a dose dependent manner (r=0.748, r=0.661, respectively, p<0.01) with the consequent decrease of patients needing THF corrective therapy (68.8% at the baseline toward 22.5% on last visit). CONCLUSION: Switch to Risperidone medication provided significant additional improvement in symptom severity, extrapyramidal side effects and need for anticholinergic medication. This suggests that one might expect better compliance in future treatment in this population of chronic schizophrenic patients.

The historical development of psychiatry in Serbia.

The authors present the development of the concept of mental disease and treatment in Serbian medicine. Serbian medieval medicine did not acknowledge fortune telling, sorcery, the use of amulets and magical rituals and formulas. These progressive concepts were confirmed by the Church and the Serbian state in what is known as Dusan's Code. The Historical data on the establishment of the first psychiatric hospital in the Balkans "Home for the Unsound of Mind" at Guberevac, Belgrade, in 1861 and its founders is reviewed. After World War I, in 1923, the Faculty of Medicine was established in Belgrade to which the coryphaei of Serbian medicine educated in Europe, mostly in France and Germany, flocked and that same year the Psychiatry Clinic of the Faculty of Medicine in Belgrade was set up. Its first seat was on the premises of the Mental Hospital in Belgrade, and it became a training base and laid the foundations of the future Neuropsychiatry Clinic in Belgrade, which in time evolved into the nursery of psychiatric professionals for all of Serbia. The most important data on the further development of psychiatry up to date are presented.

Long-term efficacy of electroconvulsive therapy combined with different antipsychotic drugs in previously resistant schizophrenia.

BACKGROUND: In treatment-resistant schizophrenia a combination of ECT with antipsychotics has been reported to have superior outcomes compared to other strategies, however the results were inconsistent. We investigated the long-term effects of the combination of unilateral, non-dominant hemisphere ECT with three antipsychotics. SUBJECTS AND METHODS: The clinical study was a naturalistic, prospective, open-labeled, active-controlled study in adult outpatients of both genders suffering from treatment-resistant schizophrenia with a follow up of 2 years. The patients received sulpiride (n=17, 100-400mg/day, PO), risperidone (n=26, 2-8 mg/day, PO) or olanzapine (n=27, 5-10mg/day, PO). Unilateral ECT was applied in 1 unit (0.5A, 0.8 mS) in six single applications, once a week and further according to the clinical need, in fortnight steps. Clinical efficacy was established using the PANSS and CGI psychometric scales. RESULTS: According to the results, the most effective treatment mode was olanzapine plus ECT, then risperidone plus ECT, while sulpiride plus ECT had lower clinical efficacy. Olanzapine plus ECT was significantly superior in all scale scores vs sulpiride plus ECT, as well as risperidone plus ECT except for PANSS-P (t=1.85, p>0.05). During the study, 38 of 70 patients were withdrawn due to treatment failure (n=21), side effects (n=6) and non-compliance (n=11). CONCLUSION: The combination of novel antipsychotics and ECT can be used safely and effectively in treatment-resistant schizophrenia.

Effectiveness of clozapine, haloperidol and chlorpromazine in schizophrenia during a five-year period.

OBJECTIVE: The aim of our study was to evaluate the effects of low doses of clozapine in flexible regime in comparison with haloperidol and chlorpromazine in long term. METHOD: The naturalistic study was prospective, active-controlled with 325 adult outpatients of both genders (140 females), with mean year age of 34.8 (range 21-57), suffering from chronic schizophrenia. The first onset of illness was at the mean of 27.9 years (range 17-38), and subjects had the mean year age of 4.1+/-0.5 previous relapses. The patients were allocated to receive haloperidol (105 subjects, dose range 2-15 mg), chlorpromazine (n=105, 100-400 mg) or clozapine (n=115, 75-600 mg). The scores of psychometric instruments (GWB, PANSS, CGI) were regularly assessed during 5 year period. RESULTS: The sixty-six responders were included in per-protocol analysis: 12, 10 and 16 with positive and 7, 6 and 15 with negative schizophrenic syndrome in haloperidol, chlorpromazine and clozapine group, respectively. The statistically significant differences in all psychometric scores was found, for both schizophrenic syndromes, favoring clozapine. The distribution of eighteen different types of adverse events, which we noted, were significantly different among treatment groups ( chi2=315.7, df=34, p<0.001). Clozapine was safer and had fewer adverse effects (average of 0.9 adverse events per patient) than haloperidol (2.7) and chlorpromazine (3.2). CONCLUSIONS: Clozapine, in low doses of flexible regime, in long term (five years) showed better effectiveness in chronic schizophrenics with positive and negative symptoms than typical antipsychotics.

Effectiveness of clozapine, haloperidol and chlorpromazine in schizophrenia during a five-year period / Eficácia da clozapina, haloperidol e clorpromazina na esquizofrenia em um período de cinco anos

OBJECTIVE: The aim of our study was to evaluate the effects of low doses of clozapine in flexible regime in comparison with haloperidol and chlorpromazine in long term. METHOD: The naturalistic study was prospective, active-controlled with 325 adult outpatients of both genders (140 females), with mean year age of 34.8 (range 21-57), suffering from chronic schizophrenia. The first onset of illness was at the mean of 27.9 years (range 17-38), and subjects had the mean year age of 4.1±0.5 previous relapses. The patients were allocated to receive haloperidol (105 subjects, dose range 2-15 mg), chlorpromazine (n=105, 100-400 mg) or clozapine (n=115, 75-600 mg). The scores of psychometric instruments (GWB, PANSS, CGI) were regularly assessed during 5 year period. RESULTS: The sixty-six responders were included in per-protocol analysis: 12, 10 and 16 with positive and 7, 6 and 15 with negative schizophrenic syndrome in haloperidol, chlorpromazine and clozapine group, respectively. The statistically significant differences in all psychometric scores was found, for both schizophrenic syndromes, favoring clozapine. The distribution of eighteen different types of adverse events, which we noted, were significantly different among treatment groups ( ÷2=315.7, df=34, p<0.001). Clozapine was safer and had fewer adverse effects (average of 0.9 adverse events per patient) than haloperidol (2.7) and chlorpromazine (3.2). CONCLUSIONS: Clozapine, in low doses of flexible regime, in long term (five years) showed better effectiveness in chronic schizophrenics with positive and negative symptoms than typical antipsychotics.

OBJETIVO: O propósito deste estudo foi avaliar os efeitos de baixas doses de clozapina em regime flexível comparando com o uso de haloperidol e clorpromazina por período de 5 anos. MÉTODO: Um estudo prospectivo naturalístico, ativo-controlado foi realizado com 325 pacientes com idade média de 34,8 (variância 21-57). Todos com diagnóstico de esquizofrenia. No primeiro surto da doença os pacientes apresentavam idade média de 27,9 anos (variância 17-38) e os surtos subsequentes apareceram em média 4,1±0,5 anos após. Os pacientes foram orientados a receberem haloperidol (105 pacientes com dose entre 2 e 15 mg), clorpromazina (105 pacientes com dose entre 100 e 400 mg) e clozapina (115 pacientes com dose entre 75 e 600 mg). Os instrumentos psicométricos utilizados (GWB, PANSS e CGI) foram regularmente empregados durante os 5 anos do estudo. RESULTADOS: Os 66 pacientes respondedores ao tratamento foram incluídos no protocolo de análise: 12, 10 e 16 apresentavam síndrome esquizofrênica positiva e 7, 6 e 15 síndrome negativa esquizofrênica com haloperidol, clorpromazina e clozapina, respectivamente. Diferenças estatísticas significantes foram observadas em todas as avaliações psicométricas em ambas síndromes esquizofrênicas favorecendo a clozapina. A distribuição de 18 tipos de efeitos colaterais observados foi diferente de modo significativo entre os 3 grupos estudados. A clozapina foi a droga que apresentou menos efeitos colaterais. CONCLUSÃO: A clozapina administrada por longo termo em pequenas doses em regime flexível apresenta melhor eficácia nas síndromes esquizofrênicas quando comparada a outras drogas antipsicóticas.

[Epilepsy treatment in Serbian medieval monastery hospitals].

Emperor John III Ducas Vatatzes (ruled from 1222-1254) and his son Theodore II Lascaris (ruled from 1254-1258) both suffered from epilepsy. On his journeys to Nicaea, St Sava visited emperors Theodore I Lascaris (ruled from 1204-1222) and John II Vatatzes, who richly rewarded him, which was probably of crucial importance for the foundation of hospitals in the Monastery of Hilandar and the Monastery of Studenica These hospitals had special departments for the treatment of patints with epilepsy. According to researches conducted up-to-date, these departments are considered to be the oldest institutions for epilepsy treatment. Monastery hospitals in the West served primarily as a shelter for the poor and patients with chronic incurable diseases. The development of Serbian monastery hospitals was a long process and it included institutions that lasted for a long time (for over two centuries) in which, among others, those affected by epilepsy were cured.

[Dr Mladen Jankovic - personality and work (1831-1885)].

Dr Mladen Jankovic was born in Kanjiza, in the district of Banat, in 1831. He completed the Hungarian High School in Segedin, and graduated from the Faculty of Medicine in Budapest, in 1856. Upon graduation, he moved to Serbia, where he was assigned to the position of a physician in the town of Krusevac. One year later, he was urgently transferred from Krusevac and appointed a regional physician in the town of Jagodina. After succeeding in eradicating local epidemics there, he was urgently transferred to the town of Kragujevac. Dr Mladen Jankovic was the fourth regional physician in Kragujevac, from 1861 to 1865. As an expert on the issues of health legislation and health service organisation in the Austro-Hungarian Empire, Dr Mladen Jankovic was again transferred to Belgrade in 1865, to the position of the City Administration physician. Due to the fact that the Mental Asylum "Dom za s uma sisave", which was founded in 1861, required a professional guidance, Dr Jankovic was appointed Director of this psychiatric institution in the same year. Namely, it was known that Dr Jankovic was appointed a temporary Director and physician at the Psychiatric Hospital "Dom za s uma sisave" by a Decree issued by Mihailo M. Obrenovic, upon request of the Minister for Internal Affairs. He maintained this position for sixteen years. He prepared himself for this duty in Germany, with the leading psychiatrist at the time, Wilhelm Gruzinger. Shortly afterwards, Dr Jankovic managed to adapt the health service and protocols for the treatment of psychiatric patients to the European standards at the time. Being a gifted, intelligent physician, with broad interests and experience, he was elected President of the Serbian Medical Society in 1873. During his term of office, the activities of the Serbian Archives were improved. Dr Mladen Jankovic was, at the same time, a member of several committees that were in charge of managing the health service in Serbia at that period. Among other merits, his organisational ability as the Inspector of the Health Institutes is worth mentioning. In that capacity, he re-organised eight district hospitals and suggested purchasing the necessary equipment. He also had certain experience in diplomacy, representing his country at the Vienna Congress, in 1881. On that occasion, he was also a veterinary medicine representative of the Kingdom of Serbia. It has been widely acknowledged that Dr Mladen Jankovic was a respectful figure in Serbia, and that his life and work are incorporated in the establishment of health service in Serbia.