Effects of Haloperidol, Risperidone, and Aripiprazole on the Immunometabolic Properties of BV-2 Microglial Cells.

Microglial cells are resident macrophages in the brain that have been implicated in the pathophysiology of schizophrenia. There is a lack of studies covering the effects of antipsychotics on microglial cells. The current literature points to a possible anti-inflammatory action without clear mechanisms of action. The aim of this study is to characterize the effects of haloperidol, risperidone and aripiprazole on BV-2 microglial cells in in vitro conditions. We have used immunofluorescence and flow cytometry to analyze the classical pro and anti-inflammatory markers, while a real-time metabolic assay (Seahorse) was used to assess metabolic function. We analyzed the expression of p70S6K to evaluate the mTOR pathway activity with Western blot. In this study, we demonstrate the varying effects of haloperidol, risperidone and aripiprazole administration in BV-2 microglial cells. All three tested antipsychotics were successful in reducing the pro-inflammatory action of microglial cells, although only aripiprazole increased the expression of anti-inflammatory markers. Most significant differences in the possible mechanisms of action were seen in the real-time metabolic assays and in the mTORC1 signaling pathway activity, with aripiprazole being the only antipsychotic to reduce the mTORC1 activity. Our results shed some new light on the effects of haloperidol, risperidone and aripiprazole action in microglial cells, and reveal a novel possible mechanism of action for aripiprazole.

Prescribing patterns in adolescent psychiatric practice: an important role of antipsychotics.

BACKGROUND: Many adolescents affected by psychiatric disorders require pharmacological treatment. Knowing which medication is being used is of utmost importance. Our main objective was to gain insight into prescribing patterns at the Department of child and adolescent psychiatry, Clinical Hospital Centre Rijeka. In addition, we looked for potential differences between adolescents regarding their pharmacotherapy status. SUBJECTS AND METHODS: The data from medical charts of 227 adolescents (55% females), age 12-18 years (16.4±1.18) were analysed. All of them were treated as outpatients during one year period (2014/15). Medical charts were obtained from the computerized archive system of Clinical Hospital Centre. Prescribed drug patterns were taken into account if patients have been taking medication for at least one month. RESULTS: Most of the patients, 162 (71.4%), were treated with psychiatric medication. In the pharmacologically treated group, adolescents were older (t=-4.678; p<0.001), predominately male (χ2=5.175, p=0.023) and hospitalized (χ2=20.612, p<0.0001). Accordingly, male (OR=2.09, P<0.05) and hospitalized (OR=15.32, P<0.001) adolescents were more disposed to be medicated. Psychotic disorder was the most commonly diagnosed disorder (51 patients). There were 454 different prescribing patterns, mostly prescribed antipsychotics, 36.6% of all prescriptions; followed by 31.5% anxiolytics' and 23.7% antidepressants' prescriptions. However, number of patients receiving antipsychotics, anxiolytics and antidepressants was quite similar (103: 110: 99). The highest number of patients was treated with sertraline (58), followed by those treated with risperidone (48). Majority of the patients (104/227) were treated with polytherapy. CONCLUSION: Prescribing psychiatric pharmacotherapy for adolescents is a common clinical practice. Adolescents that were prescribed pharmacotherapy were significantly older; hospitalized and male adolescents were more prone to be medicated. Antipsychotics were most frequently prescribed drugs. The prescribing patterns are generally consistent with international trends and guidelines; however caution regarding high proportion of polytherapy is necessary.

Retrospective Analysis of the Effectiveness and Tolerability of Long-Acting Paliperidone Palmitate Antipsychotic in Adolescent First-Episode Schizophrenia Patients.

OBJECTIVE: The aim of this study was to explore the effectiveness and tolerability of long-acting paliperidone palmitate antipsychotic in adolescent first-episode schizophrenia patients while comparing the results with the oral antipsychotic risperidone. METHODS: This study is a retrospective, noninterventional study to assess the effectiveness and tolerability of long-acting injectable antipsychotic paliperidone palmitate in first-episode adolescent patients during the first 12 months of treatment compared with the oral antipsychotic risperidone. The data include general sociodemographic characteristics, number of hospitalizations, side effects, and the following clinical scales: Positive and Negative Syndrome Scale (PANSS), Personal and Social Performance Scale (PSP), Clinical Global Impression Improvement and Severity (CGI-I and CGI-S), and Treatment Satisfaction Questionnaire for Medication (TSQM). RESULTS: During the 12-month study period significant improvement was registered in patients receiving both paliperidone palmitate and risperidone in the following scales: PANSS, PSP, CGI-I, and CGI-S. Patients receiving paliperidone palmitate had significantly greater improvement in PANSS, CGI-S, and PSP compared with the risperidone group. Patients receiving risperidone had significantly higher number of hospitalizations than the patients receiving paliperidone palmitate. The TSQM revealed that the patients who were receiving paliperidone palmitate achieved significantly higher scores on the convenience scale, global satisfaction, and on the overall result, whereas no difference was observed on the effectiveness scale. There were several side effects reported for paliperidone (5.5% hyperprolactinemia, 5.5% weight gain) and risperidone (5.5% hyperprolactinemia, 16.7% weight gain). CONCLUSIONS: In conclusion, paliperidone palmitate seems to be safe and effective in adolescent patients. Furthermore, it compared favorably with risperidone in the clinical response, side effects, and hospitalizations.

Effects of Psychosocial Day Care Programme on Quality of Life in Patients Affected with Schizophrenia - a Prospective Study.

BACKGROUND: The basic aim of this prospective research was to establish the effect of psychosocial day care programme on the therapy outcomes in patients with schizophrenia. SUBJECTS AND METHODS: While 115 patients with schizophrenia were invited to participate, 100 of them completed the study and were subdivided into two groups. In addition to pharmacotherapy, the experimental group only (N=50) was integrated into a day-hospital-based psychosocial day care programme. The instruments were applied in three phases: the first measurement for experimental group subjects took place on the first day of psychosocial day-care programme, while for the control group subjects the same was performed on the last day of inpatient care. The second measurement for the experimental group was performed in the end of psychosocial day-care programme, while for the control group patients it occurred four months after inpatient treatment. The third measurement was carried out six months after the second one. The following instruments were applied: General Demographic Questionnaire at the first measurement, Manchester Short Assessment of Quality of Life-MANSA both at the first and third measurement, and Positive and Negative Symptoms Scale-PANSS at all three measurements. RESULTS: Experimental group patients showed a statistically significant increase in quality of life outcomes as well as statistically significant decrease in positive symptoms and general psychopathology at all three measurements and with regard to the control group. As to the negative symptoms, only the third measurement revealed a statistically significant difference. CONCLUSION: The results obtained indicate that the adjuvant treatment of psychosocial day care programme has a positive effect on treatment outcomes: on the increase of the patients' quality of life, and, to some extent, on the decrease of symptom intensity in positive symptoms in schizophrenia spectrum. However, the effect of psychosocial day-care programme on the negative symptoms was proved to be considerably smaller.

Cortical gray matter loss in schizophrenia: Could microglia be the culprit?

Cortical gray matter loss in schizophrenia remains a great therapeutic difficulty. Each psychotic episode causes irreversible cortical gray matter loss, that causes the patients to never regain their previous state of functioning. Microglial cells are part of the innate immune system and their functions, among others, include phagocytosis and release of neurotrophic factors. They have a key impact on developmental and plasticity-induced removal of neuronal precursors, live-but-stressed neurons and synapses, while also stimulating synaptic growth and development. We hypothesize that microglia are the culprit for the cortical gray matter loss in schizophrenia through abnormal synaptic pruning, phagocytosis of stressed neurons and lacking neurotrophic factor release. Furthermore, we propose a research that could validate the hypotheses using serum samples of first-episode early-onset patients. By measuring the serum levels of milk fat globule-EGF factor 8 (MFG-E8), subcomponent in the classical pathway of complement activation (C1q), brain-derived neurotrophic factor (BDNF), interleukin-6 (IL-6) and interleukin-10 (IL-10), we could gain an insight into the state of microglial activation during various stages of the disease. If this hypothesis is valid, new targeted drugs could be developed in order to reduce the deterioration of cortical gray matter, thereby possibly improving negative symptoms and cognitive deficits.

Virus etiology of schizophrenia: the characteristics of the "*Little Ice Age" and its consequences.

The data of the "Little Ice Age" (1500-1850) in Croatia and those which applied to human health were especially emphasized were analyzed. They are some which stand out like: importance of the sort of soil and relief, the influence of cutting down of woods and cattle-breeding and especially the war which lasted for 250 years in the territory of Croatia. The important interactions between those parameters were defined. The important correlations were also defined between freezing and long winters as well as wet springs and summers which caused starvation, malnutrition and the increase of infant mortality and also epidemics with enormous psychological stress among people in that period. The result was witch-hunting and burning (which was also advocated in the other parts of Europe) and they sometimes reached the levels of madness. Considering that such events were unknown in the earlier periods (in such proportions) and that (even today) the influence of the slow virus is emphasized in connection to the etiology of schizophrenia so why should't it be supposed that the "Litlle Ace Age" could be the cause of the larger prevalence of schizophrenia in the teritory of Croatia.

Psychiatric and health impact of primary and secondary traumatization in wives of veterans with posttraumatic stress disorder.

BACKGROUND: Along with primary traumatization, wives of PTSD-diagnosed war veterans often become victims of the altered and dysfunctional state of their partners, which adds to the severity of symptoms of primary traumatization and furthers the development of other mental disorders. The aim of this study was to compare the effects of primary and secondary traumatization in wives of PTSD-diagnosed war veterans and wives of war veterans without PTSD. SUBJECTS AND METHODS: The experimental group consisted of 154 wives whose veteran husbands had been treated in Mostar Clinical Hospital for psychotrauma-induced PTSD. The control group was formed of 77 wives of war veterans who do not suffer from PTSD. The research used a general demographic questionnaire, the Harvard Trauma Questionnaire (HTQ) and the MINI International Neuropsychiatric Interview. RESULTS: Wives of veterans with chronic PTSD experienced a significantly greater number of traumatic events (t=2.66; p=0.008) and had higher scores of PTSD symptoms (t=8.93; p<0.001). A significantly larger number of these women reported chronic somatic diseases (χ²=4.553; p=0.033). Furthermore, wives of PTSD-affected veterans significantly more frequently met criteria for current depression episode (χ²=20.65; p<0.001), past depression episode (χ²=24.40; p<0.001), depression with melancholic features (χ²=19.20; p<0.001), dysthymia (χ²=7.15; p=0.007), panic disorder with agoraphobia (χ²=5.28; p=0.022), PTSD (χ²=18.39; ss=1; p<0.001) and generalized anxiety disorder (χ²=19.58; p<0.001). This group also showed a higher level of suicidality (χ²=8.95; p=0.003). CONCLUSION: The findings of this research show how mental difficulties experienced by wives of PTSD-diagnosed war veterans affect the interrelationship of their primary and secondary traumatization.

Health-related quality of life in the patients on maintenance hemodialysis: the analysis of demographic and clinical factors.

Health-related quality of life (HRQoL) among hemodialysis (HD) patients recently became a nephrologist's focus of interest. HRQoL is an important predictor of outcome in HD patients and need to be regularly assessed. The aim of the present study was to compare the HRQoL of chronic HD patients with general population and to analyze influencing sociodemographic and clinical factors. We included 255 prevalent HD patients from four dialysis centers. HRQoL was measured with The Medical Outcomes Study Short Form 36 Health Survey Questionnaire (SF-36). This data were compared with control group (N = 132) from the general Croatian population. Comparisons of SF-36 scale scores of HD patients regarding demographic and clinical factors (age, gender, education level, dialysis vintage and diabetes) were also performed and analyzed with a multivariate regression analysis. HRQoL in prevalent HD patients was relatively low (mean Physical Component Summary, PCS = 33.7, mean Mental Component Summary, MCS = 43.0) and was lower compared to the control group from the general population in all HRQoL domains, PCS and MCS scores. Almost 53% of the HD patients had the critical score PCS < 43 + MCS < 51 as the predictor of death and hospitalization. Better HRQoL was revealed in the patients < 65 years old, males, patients with higher educational level and in the patients on maintenance HD less than one year. Age was the only statistically significant predictor of PCS and MCS. Developments of HD technology, treatment of comorbidities, continuous patients' education, social and psychological support and use of other renal replacement modalities, especially kidney transplantation, may improve the HRQoL in these patients.

Defense mechanisms in alcohol dependent patients with oral and oropharinegal cancer.

The effects of psychological factors in alcoholics with malignant tumor of the oral cavity and oropharynx are scarcely explored. The aim of the research was to examine early family relations and investigate differences in the use of defense mechanisms in alcohol dependent patients suffering from malignant tumor of the oral cavity and oropharynx compared to alcohol dependent persons without malignant tumors and healthy controls. The research included 51 alcohol dependent patients treated for malignant tumor of the oral cavity and oropharynx at the University Hospital Center Rijeka from 2005 to 2009. The control groups corresponded to the experimental group in age, sex and education level. The research used a general demographic questionnaire, the Mini International Neuropsychiatric Interview and the Revised Questionnaire of Life Style and Defense Mechanisms. The research groups showed significant differences in difficult childhood (p < 0.001) including abuse (p = 0.004). The alcohol dependent persons suffering from malignant tumors of the oral cavity and oropharynx significantly less frequently used primitive defense mechanisms of regression (p = 0.004) and displacement (p = 0.013) compared to alcoholics without malignant tumors who significantly more often used neurotic defense mechanisms - compensation (p = 0.005) and intellectualization (p < 0.001). The earliest emotional experiences and quality of family relations affect the development of defense mechanisms. These are the psychological factors in the development of oropharyngeal cancer in alcohol addicts.

Croatian war veterans in print media in 1996 and in 2006.

INTRODUCTION: The media have an important role in maintaining and creating social relations and social environment. This especially refers to the war and post-war period in which the media can form a part of the prevention context, i.e., the media can facilitate the process of recovery from war trauma, but they can also contribute to stigmatization and retraumatization. Our aim was to analyze Croatian newspaper reports about Croatian war veterans and to determine the differences in ways of dealing with the subject during 1996 and 2006. METHODS: The data were gathered by reviewing two daily papers, Novi list and Ve?ernji list and Globus weekly. The analysis included newspaper reports related to the subject of Croatian war veterans, published in the first six months of 1996 and 2006. Quantitative and qualitative methods were used to analyze both the form and the content of the reports. RESULTS: A total of 538 newspaper reports were published in the above-stated periods. In the first half of 2006 the number of reports related to the subject of Croatian war veterans dropped 6.5 percent compared to the first half of 1996. Topics prevalent at the end of the war were different from those ten years later. The 1996 articles mostly reported on activities organized by various associations, medal-awarding ceremonies, military operations etc. Ten years later the topics focused on war crimes, trials of Croatian war generals and dissatisfaction with veterans' rights and legislation. Moreover, articles relating to crime and reports about suicides and attempts of suicide increased significantly in 2006. CONCLUSION: During the ten-year period, the media image of Croatian war veterans significantly changed, which was expected owing to different social circumstances immediately after the war and ten years later. The prevalence of topics negative in tone and a lack of proactive stories reflect, but also create, a social context which can affect the process of recovery from traumatization.

High doses alprazolam induced amenorrhoea and galactorrhoea.

Alprazolam belongs in the group of anxiolytics, medicaments used for reducing anxiety. As most other drugs, it can cause various adverse events, including hormonal disturbances and imbalance. Prolactin elevation is one such hormonal adverse event that can lead to galactorrhoea, or abnormal milk discharge from the breast and amenorrhoea. In this case report we will present the case of a female patient that developed galactorrhoea while treated with alprazolam, after all physical factors that can also cause these symptoms were excluded.

Influence of personality traits on sexual functioning of patients suffering from schizophrenia or depression.

Aim of this research was to establish effects and influence of personality traits on sexual functioning of schizophrenic and depressive patients, compared to healthy individuals. 300 participants were included in this research. For patients suffering from schizophrenia it was established that the more they are open to experience and the less they are neurotic their sexual drive is stronger. For patients suffering from depression it was established that the more they are open to experience and conscientious and the less they are agreeable their sexual drive is stronger. Furthermore, higher openness is a significant predictor for easier sexual arousal and the more those patients are conscientious and the less they are agreeable easier is for them to achieve orgasms. Personality traits proved to be significant predictors of sexual functioning in schizophrenic and depressive patients, but not in healthy individuals.

Stigmatization of patients suffering from schizophrenia.

For the general public, but also for healthcare professionals, schizophrenia is still one of those areas of medicine connected with feelings of unease, fear and prejudice. These feelings lead to stigmatization and discrimination which are unjust processes which put patients suffering from mental illnesses into undesirable and unequal positions. Aim of this research was to establish the extent of stigmatization of mentally ill patients among the population of healthcare professionals and future healthcare professionals and if they differ from general population. Results show that stigmatization of schizophrenic patients is high among all included populations. Although there were no statistical differences between groups regarding the assessment of schizophrenic patients, nurses employed in psychiatric wards exhibited a tendency towards higher acceptance of schizophrenic patients, as well as better understanding of that illness. This data emphasizes a growing need for continuous education of general population but also of healthcare professionals.

Ziprasidone as a possible cause of cleft palate in a newborn.

Use of antipsychotic medication during the entire course of pregnancy in patients suffering from schizophrenia is frequently necessary as discontinuation of therapy can lead to relapse of the illness which can be far more severe for the mother, but also for the fetus. That is the case why third generation antipsychotics, so called atypical antipsychotics, are also being used during the pregnancy, but their effects are not fully researched. Use of ziprasidone as a third generation antipsychotic, and its effects during the pregnancy in patients suffering from various mental illnesses is very rarely described in scientific literature. There is even fewer information regarding eventual adverse events of ziprasidone in newborn babies of mothers that have been treated with ziprasidone during the entire course of pregnancy. This paper will be based around a case report of a female patient suffering from schizophrenia who has been treated with ziprasidone during the entire course of her pregnancy and whose newborn baby was diagnosed with a cleft palate (palatoschisis) at the time of birth.

Pregnancy and atypical antipsychotics.

Scientific research aiming at discovering new generations of effective medications is a common practice in medicine, and psychiatric research is no exception. Antipsychotics are used to treat chronic mental illnesses such as schizophrenia. The new generation of antipsychotics (atypicals) gradually reveal their advantages in comparison to the older generation of antipsychotics (conventional, typicals) and are increasingly applied to the everyday practice. Although there are no differences in the therapeutic effectiveness between the two groups mentioned, atypical antipsychotics have become the drugs of choice. A certain number of women in their reproductive age suffer from schizophrenia and other mental illnesses which demand antipsychotic treatment. Atypical antipsychotics have been available on the market since the mid 90's so the experience in the application of these medicaments in treating pregnant women is relatively modest. This study will present our own experience in the treatment of a pregnant woman suffering from schizophrenia, who was treated with ziprasidone for the duration of her pregnancy. The psychotic symptoms remained in remission throughout the whole pregnancy period, during labour and after the birth. The pregnancy course remained normal all through to the birth, which was carried out naturally and normally. A healthy baby was born within the term expected.

Changes of adolescents' defence mechanisms during the first year of high school education.

The goal of this study was to analyse the defence mechanism's changes during adolescent's adaptation to the new schooling terms at the first year in high school. Sample of 266 students, mean age 15, have been included in the research. Kellerman's Life Style Questionnaire (LSQ) was administred for measuring defence mechanisms at the beginning and at the end of the school year. Results show that regression and reactive formation are changing at most; regression raises (p < 0.005) while reactive formation decreases (p < 0.000). Boys used repression, while girls reactive formation more frequently in both measuring. Displacement was 'male" defence in the first measuring; but at repeated measuring this difference in sex vanished. The sources of anxiety can be found partly in new school environment and in adolescent's effort to "solve the problem" with sexual impulses and aggression using different sets of defences.