Effects of Alpha-Lipoic Acid Supplementation on Plasma Adiponectin Levels and Some Metabolic Risk Factors in Patients with Schizophrenia.

Adiponectin is an adipocyte-derived plasma protein with insulin-sensitizing and anti-inflammatory properties and is suggested to be a biomarker of metabolic disturbances. The aim of this study was to investigate the effects of alpha-lipoic acid (ALA) on plasma adiponectin and some metabolic risk factors in patients with schizophrenia. The plasma adipokine levels (adiponectin and leptin), routine biochemical and anthropometric parameters, markers of oxidative stress, and the serum phospholipid fatty acid profile in eighteen schizophrenic patients at baseline, in the middle, and at the end of a 3-month long supplementation period with ALA (500 mg daily) were determined. A significant increase in the plasma adiponectin concentrations, as well as a decrease in fasting glucose and aspartate aminotransferase activity (AST), was found. Baseline AST activity was independently correlated with the adiponectin concentrations. Our data show that ALA can improve plasma adiponectin levels and may play a potential role in the treatment of metabolic risk factor in patients with schizophrenia. Future randomized controlled trials are needed to confirm these preliminary investigations.

Tryptophan Hydroxylase 1 Variant rs1800532 is Associated with Suicide Attempt in Serbian Psychiatric Patients but does not Moderate the Effect of Recent Stressful Life Events.

Tryptophan hydroxylase 1 (TPH1) gene, coding for serotonin synthesizing enzyme, and recent stressful life events (SLEs) have been commonly associated with suicidal behavior. TPH1 has been also hypothesized to be involved in stress-response mechanisms. The aim of this study was to assess TPH1 variant rs1800532 and its possible interaction with recent SLEs as risk factors for suicide attempt (SA) in Serbian psychiatric patients, including 165 suicide attempters and 188 suicide nonattempters. rs1800532 and recent SLEs were independently associated with SA, while rs1800532 did not moderate the effect of recent SLEs on SA vulnerability among Serbian psychiatric patients.

Numbers of early career psychiatrists vary markedly among European countries.

In the field of psychiatry the decline of recruitment and brain-drain are currently one of the most discussed topics among stakeholders on national and European level. Even though comprehensive data on psychiatric training in Europe have been already reported, no data are available on even the approximate number of early career psychiatrists (ECPs). With this objective in mind, the Early Career Psychiatrists Committee of the European Psychiatric Association (EPAECPC) and the European Federation of Psychiatric Trainees (EFPT) have undertaken a survey. Based on the methodology used, the total number of ECPs in all European countries was 46 144 with the average number of ECPs being 5.5/100 000 country inhabitants. The actual numbers in this respect varied greatly among countries from 0.4 and 0.6 ECPs/100 000 in Azerbaijan resp. Russia; to 20.4 and 28.4 ECPs/100 000 in Norway resp. Switzerland. An obvious East-West gradient with increasing numbers of ECPs when moving from East to West, and from South to North were found, mirroring the economic strength of European countries. This is the first study to specifically explore the number of ECPs across Europe which might have key implications for planning and establishing recruitment activities and for developing strategies for prevention of brain-drain, such as improvement of educational system and enlargement of professional opportunities.

Joint effect of ADARB1 gene, HTR2C gene and stressful life events on suicide attempt risk in patients with major psychiatric disorders.

OBJECTIVES: Adenosine to inosine RNA editing, serotonin 2C receptor (HTR2C), and stressful life events (SLEs) have all been implicated in suicidal behaviour. We examined the main and moderating effects of RNA editing (ADAR, ADARB1) and HTR2C genes, childhood trauma (CT), recent SLEs and psychiatric disorders as contributors to suicide attempt (SA) vulnerability. METHODS: Study included 165 suicide attempters and 188 suicide non-attempters, all diagnosed with one of major psychiatric disorders. CT and recent SLEs were assessed using Early Trauma Inventory-Self Report and List of Threatening Experiences Questionnaire, respectively. Selected ADAR and ADARB1 tag-variants, and HTR2C rs6318 were pre-screened for association with SA, while generalized linear models and backward selection were applied to identify individual and interacting SA risk factors. RESULTS: ADARB1 rs9983925 and rs4819035 and HTR2C rs6318 were associated with SA. The best minimal model found emotional abuse, recent SLEs, rs9983925 and rs6318 as independent SA risk factors, and general traumas as a factor moderating the effect of psychiatric disorders and emotional abuse. CONCLUSIONS: SA vulnerability in psychiatric patients is related to the joint effect of ADARB1 and HTR2C variants, the existing mood disorder and the cumulative exposures to a various childhood and recent stressful experiences.

Cannabis and psychosis revisited.

The association between cannabinoids and psychosis has been known for almost a thousand years, but it is still speculated whether cannabis use may be a contributory cause of psychosis, that is, whether it may precipitate schizophrenia in those at risk. In this paper, we will briefly present the data from individual longitudinal studies in the field, together with the factors that are considered important for the association of cannabis abuse and occurrence of schizophrenia and prevention opportunities in the target population. The reviewed studies clearly suggest that cannabis abuse predicts an increased risk for schizophrenia, particularly in young adults. They underline both the need to create adequate prevention measures and consequently avoid the occurrence of the disease in the young at risk. Particular attention should be additionally devoted toward encouraging the young presenting with psychotic symptoms to stop or, at the very least, reduce the frequency of cannabis abuse. The issues are undoubtedly to be addressed by the health care system in general.

Effect of alpha-lipoic acid supplementation on oxidative stress markers and antioxidative defense in patients with schizophrenia.

BACKGROUND: The purpose of this study was to examine the effects of alpha-lipoic acid (LA) supplementation on oxidative stress markers in patients with schizophrenia. SUBJECTS AND METHODS: Eighteen (18) medicated patients with schizophrenia and 38 healthy controls received daily supplements of LA (500 mg/day) for three months. At baseline, 45th and 90th days of supplementation, venous blood collected for analysis of oxidative stress markers [superoxide anion (O2(•-)), thiobarbituric acid-reactive substances (TBARS) and advanced oxidation protein products (AOPP)] and antioxidative defense markers [superoxide dismutase (SOD), total sulfhydryl groups (-SH) and total antioxidant status (TAS)]. RESULTS: Increased plasma TBARS, TAS, SH groups levels and SOD activity were found in schizophrenic patients compared to control group. LA supplementation significantly reduced TBARS, AOPP and improved TAS levels in healthy subjects, while there were no significant differences in patients group. SH groups increased after 45 days and decreased to baseline levels after 90 days of supplementation in the control group. SOD activity decreased significantly in patients group after 45 days and 90 days of supplementation. After initial rose SOD activity in control group, decreased to baseline levels found after 90 days. CONCLUSION: LA supplementation decreased lipid peroxidation and oxidative damage of proteins and improved non-enzymatic antioxidant capacity in healthy controls. No significant changes were observed on oxidative damage in patients with schizophrenia.

Algorithms in psychiatry: state of the art.

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

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

BACKGROUND: The variations in proinflamatory cytokine levels have been associated with schizophrenia (SCH), duration of illness, psychopathology and treatment. The aim of the study was to investigate serum levels of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) in schizophrenic patients during exacerbation and remission, and its association with course of illness and therapy. SUBJECTS AND METHODS: We measured serum levels of IL-6 and TNF-α in 43 schizophrenic patients in exacerbation and remission and compared them to 29 healthy controls, matched by sex, age, body mass index (BMI) and smoking habits. The severity of psychopathology was assessed using the Positive and Negative Syndrome Scale (PANSS). RESULTS: There was no difference in levels of IL-6 and TNF-α in exacerbation compared to remission in schizophrenic patients. IL-6 was higher and TNF-α was lower in schizophrenic patients in both exacerbation and remission in comparison with healthy controls. TNF-α in exacerbation was in negative correlation with IL-6 in remission. No statistical significance was found between levels of cytokines and sex, age, BMI, smoking habits, antipsychotic medication, duration of treatment and duration of illness. IL-6 levels were in positive correlation with the age of onset and the duration of untreated psychosis. In schizophrenic patients on adjunctive treatment with mood stabilizers, TNF-α levels increased in remission. CONCLUSION: Our results suggest that the connection between schizophrenia, cytokines and medication is multifaceted, and not necessarily linear. Adjunct mood stabilizers not only ameliorate psychopathology, but might convey immunomodulatory effects as well. Further longitudinal studies could elucidate potential beneficial effect of combined therapy in treatment of SCH.

Melancholic and atypical major depression--connection between cytokines, psychopathology and treatment.

BACKGROUND AND PURPOSE: Growing scientific evidence indicates that there is a correlation between depression and alternations in the immune system. The main aim of the study was to investigate serum levels of Interleukin-6 (IL-6) and Tumour Necrosis Factor-alpha (TNF-α) in melancholic and atypical depressive patients during acute exacerbations of illness, compared to healthy subjects. The secondary aim was to explore a possible association between cytokine levels and clinical characteristics, as well as total duration of prior antidepressant treatment. METHOD: We measured serum levels of IL-6 and TNF-α in 47 patients suffering from major depressive disorder (MDD) (29 melancholic and 18 atypical) in exacerbation of illness, compared to 39 healthy controls, matched by sex, body mass index (BMI) and smoking habits. Serum levels of IL-6 and TNF-α were measured by enzyme-linked immunosorbent assay (ELISA). The severity of psychopathology was assessed using the Hamilton Depression Rating Scale (HDRS). RESULTS: IL-6 was significantly elevated in melancholic depressive patients (MDD-M) compared to healthy controls, while no difference was found between the patients with atypical depression (MDD-A) and the healthy group. Lower TNF-α serum level was found both in melancholic and in patients with atypical depression, compared with healthy subjects. We detected a positive correlation between cytokine levels in atypical, but not in melancholic subjects. Sex, age, smoking habits and BMI were not associated to cytokine levels in neither group. Clinical parameters (duration of illness, current episode, age of onset) were related to cytokine levels in atypical depression, while the duration of lifetime exposure to antidepressant treatment correlated to IL-6 serum levels in both melancholic and atypical depression. CONCLUSION: Our results suggest that the difference in pro-inflammatory cytokine levels could reflect a biological difference between melancholic and atypical depression. A positive correlation between the cytokines (TNF-α and IL-6) observed in depressive patients with atypical features, might be influenced by chronic course of illness, while IL-6 elevation could represent a state indicator for acute exacerbation, especially in melancholic patients. Total duration of antidepressant treatment could be a relevant factor influencing the immune status of patients who suffer either from melancholic or atypical depression.

Antipsychotics--history of development and field of indication, new wine--old glassess.

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".

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

BACKGROUND: The attitudes of medical professionals towards homosexuals can influence their willingness to provide these individuals with medical help. The study evaluated the medical professionals' knowledge about homosexuality and their attitudes towards it. SUBJECTS AND METHODS: The sample consisted of 177 participants (physicians n=79 and students n=98). The study respondents anonymously completed three questionnaires (socio-demographic questionnaire, the questionnaire on knowledge, and the questionnaire on attitudes towards homosexuals). RESULTS: Male and religious participants showed a lower level of knowledge and a greater tendency to stigmatize. Furthermore, the subjects who knew more about homosexuality tended to hold less stigmatizing attitude. Age group, specialty (psychiatry, gynecology, internal medicine and surgery), and student's/physician's status had no effect on stigmatization. The study showed that the final year students/ residents had more knowledge than the second year students/specialists did. Knowledge had significant negative predictive effect on attitudes in the analyzed predictive model. CONCLUSIONS: To our knowledge, this has been the first study in Serbia and Eastern Europe, which provides information on knowledge and attitudes of health professionals towards homosexuality. We would like to point out the degree of knowledge on homosexuality as a possible, but not exclusive tool in shaping the attitudes towards homosexuals and reducing stigmatization. However, regardless of the personal attitude, knowledge and variable acceptance of the homosexuals' rights, medical professionals' main task is to resist discriminative behavior and provide professional medical help to both homosexual and heterosexual patients.

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

In the last two decades, Serbia has had to deal with multiple social and economic problems reflecting on society's demographics and seemed to weaken its core cell - the family. The paper describes the framework of family therapy in clinical practice and research, within the recent transition of the Serbian family. Family therapy treatment in Serbia uses the systemic family therapy (SFT) approach, applied according to the standards of the European Association for Psychotherapy. A large number of professionals who practise in Serbia hold European qualifications, setting high standards in education, clinical practice, and research. Although SFT is also available in the private sector, the majority of patients are still treated in state institutions. Family therapy is often used for adults and adolescents with psychosis and addictions in psychiatric hospital settings. However, in counselling centres it is used for marital and relationship problems. Interestingly, family therapy has recently started to emerge as a more frequent tool in consultation-liaison, particularly psycho-oncology but also in correctional institutions. The clinical practice and research interests are interlinked with changes in social settings.

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

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

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.