Strategies, processes, outcomes, and costs of implementing experience sampling-based monitoring in routine mental health care in four European countries: study protocol for the IMMERSE effectiveness-implementation study.

BACKGROUND: Recent years have seen a growing interest in the use of digital tools for delivering person-centred mental health care. Experience Sampling Methodology (ESM), a structured diary technique for capturing moment-to-moment variation in experience and behaviour in service users' daily life, reflects a particularly promising avenue for implementing a person-centred approach. While there is evidence on the effectiveness of ESM-based monitoring, uptake in routine mental health care remains limited. The overarching aim of this hybrid effectiveness-implementation study is to investigate, in detail, reach, effectiveness, adoption, implementation, and maintenance as well as contextual factors, processes, and costs of implementing ESM-based monitoring, reporting, and feedback into routine mental health care in four European countries (i.e., Belgium, Germany, Scotland, Slovakia). METHODS: In this hybrid effectiveness-implementation study, a parallel-group, assessor-blind, multi-centre cluster randomized controlled trial (cRCT) will be conducted, combined with a process and economic evaluation. In the cRCT, 24 clinical units (as the cluster and unit of randomization) at eight sites in four European countries will be randomly allocated using an unbalanced 2:1 ratio to one of two conditions: (a) the experimental condition, in which participants receive a Digital Mobile Mental Health intervention (DMMH) and other implementation strategies in addition to treatment as usual (TAU) or (b) the control condition, in which service users are provided with TAU. Outcome data in service users and clinicians will be collected at four time points: at baseline (t0), 2-month post-baseline (t1), 6-month post-baseline (t2), and 12-month post-baseline (t3). The primary outcome will be patient-reported service engagement assessed with the service attachment questionnaire at 2-month post-baseline. The process and economic evaluation will provide in-depth insights into in-vivo context-mechanism-outcome configurations and economic costs of the DMMH and other implementation strategies in routine care, respectively. DISCUSSION: If this trial provides evidence on reach, effectiveness, adoption, implementation and maintenance of implementing ESM-based monitoring, reporting, and feedback, it will form the basis for establishing its public health impact and has significant potential to bridge the research-to-practice gap and contribute to swifter ecological translation of digital innovations to real-world delivery in routine mental health care. TRIAL REGISTRATION: ISRCTN15109760 (ISRCTN registry, date: 03/08/2022).

Retention in outpatient treatment of alcohol dependence based on the Lesch`s typology and the involvement of a close person.

OBJECTIVES: Retention in alcohol-dependence treatment is an indicator of successful treatment. The aim of this study was to analyze Lesch's typology of alcohol dependence (LAT) and the participation of close people as potential predictors of retention in outpatient treatment. METHODS: Participants were included in the study according to the inclusion criteria. Data were collected over eight visits during a 6-month period. The primary outcome was retention in treatment during the 6-month follow-up period. RESULTS: 119 patients were involved in the study, and 84 (70.6 %) of those patients remained in treatment up to the 6th month. Analysis of retention was performed for the Lesch I, II, and III types, as the type IV patients were underrepresented and had different baseline characteristics. Higher retention was found for Lesch I type patients (78.4 %) in comparison to the merged II and III groups. The presence of close people at planned visits had a significant effect on treatment persistence. CONCLUSIONS: We found no significant difference in the treatment retention of alcohol-dependent patients at the 6-month follow-up. However, a more comprehensive survival analysis indicated a trend of different retention dynamics between the Lesch I and merged Lesch II and III subgroups. Baseline severity of dependence measured by AUDIT score had no significant effect on treatment retention (Tab. 1, Fig. 3, Ref. 35).

Association of CD33 rs3865444:C˃A polymorphism with a reduced risk of late-onset Alzheimer's disease in Slovaks is limited to subjects carrying the APOE ε4 allele.

CD33 rs3865444:C>A single nucleotide polymorphism (SNP) has been previously associated with the risk of late-onset Alzheimer's disease (LOAD); however, the results have been inconsistent across different populations. CD33 is a transmembrane receptor that plays an important role in AD pathogenesis by inhibiting amyloid ß42 uptake by microglial cells. In this study, we aimed to validate the association between rs3865444 and LOAD risk in the Slovak population and to evaluate whether it was affected by the carrier status of the major LOAD risk allele apolipoprotein (APOE) ε4. CD33 rs3865444 and APOE variants were genotyped in 206 LOAD patients and 487 control subjects using the polymerase chain reaction-restriction fragment length polymorphism method and direct sequencing, respectively. Logistic regression analysis revealed a significant association of rs3865444 A allele with a reduced LOAD risk that was only present in APOE ε4 allele carriers (AA + CA versus CC: p = .0085; OR = 0.45; 95% CI = 0.25-0.82). On the other hand, no such association was found in subjects without the APOE ε4 (p = .75; OR = 0.93; 95% CI = 0.61-1.42). Moreover, regression analysis detected a significant interaction between CD33 rs3865444 A and APOE ε4 alleles (p = .021 for APOE ε4 allele dosage and p = .051 for APOE ε4 carriage status), with synergy factor (SF) value of 0.49 indicating an antagonistic effect between the two alleles in LOAD risk. In conclusion, our results suggest that CD33 rs3865444:C˃A substitution may reduce the risk of LOAD in Slovaks by antagonizing the effect conferred by the major susceptibility allele APOE ε4.

A Novel Association of Polymorphism in the ITGA4 Gene Encoding the VLA-4 α4 Subunit with Increased Risk of Alzheimer's Disease.

Alzheimer's disease (AD) is the most prevalent cause of dementia in elderly people worldwide. Many studies support the hypothesis that the inflammation of the CNS contributes to the neurodegeneration and disease progression. The integrin molecule α4ß1, also known as very late antigen 4 (VLA-4), belongs to adhesion molecules that activate the inflammatory process through the migration of immune cells into the CNS. Therefore, the objective of our study was to analyze the association between two polymorphisms located in the ITGA4 gene encoding the α4 subunit of VLA-4 and the risk of AD. 104 late-onset AD patients and 206 control subjects from Slovakia were genotyped for ITGA4 gene SNP polymorphism rs113276800 (-269C/A) and rs1143676 (+3061A/G). The same study cohorts were also genotyped for the APOE-ε4, which is a known genetic factor associated with increased risk of AD developing. ITGA4 polymorphism analysis revealed significantly higher frequency of the +3061AG carriers in AD group compared to the controls (P ≤ 0.05). Following the APOE-ε4 stratification of study groups, the association remained significant only in APOE-ε4 noncarriers. Our study suggests a novel association of ITGA4 +3061A/G polymorphism with AD and its possible contribution to the disease pathology.

Theory of mind - not emotion recognition - mediates the relationship between executive functions and social functioning in patients with schizophrenia.

BACKGROUND: Dysfunction of social-cognitive abilities is one of the hallmark features of schizophrenia and is associated with neurocognition and social functioning. The Green and Nuechterlein model proposed that social cognition mediates the relationship between neurocognition and functional outcome. We tested this hypothesis in schizophrenia patients in the everyday clinical setting. SUBJECTS AND METHODS: Social cognition, executive function and social functioning were assessed in a group of 43 patients with schizophrenia or schizoaffective disorder using a range of measures. RESULTS: Theory of mind was associated with executive functions and social functioning. Results of our mediation analysis suggested that the relationship between executive functions and social functioning was mediated by theory of mind. No relationships between emotion recognition and the domains of social functioning were found. CONCLUSIONS: In line with prior research, zero-order associations were found between theory of mind and social functioning. Theory of mind was a mediator of the relationships between neurocognition and social functioning. Our results suggest that theory of mind should be a potential target of interventions to improve social functioning.

Categorization of psychoactive substances into "hard drugs" and "soft drugs": a critical review of terminology used in current scientific literature.

BACKGROUND: Precise terminology and definitions are important components of scientific language. Although the terms "hard drugs" and "soft drugs" are used widely by professionals, neither the International Classification of Diseases nor the Diagnostic and Statistical Manual classify psychoactive substances into the categories "hard" and "soft." OBJECTIVES: To analyze the occurrence of the terms "hard drugs" and "soft drugs" in recent scientific literature and to establish the degree of consensus in labeling psychoactive substances as "hard" or "soft." METHODS: A critical review of scientific papers listed in PubMed and Scopus between 2011 and 2015. Three hundred thirty-four articles were initially identified as potentially relevant for review, 132 of which were included in the final analysis. RESULTS: One hundred twenty-four articles used the term "hard drugs" and 84.7% provided examples of substances considered "hard." Forty-four articles used the term "soft drugs" and 90.9% provided examples of substances considered "soft." Citations of relevant articles supporting categorization as "hard" or "soft" were not given in 90% of the articles. The authors often provided no or only very sparse information on their reasons for considering specific drugs as "hard" or "soft." CONCLUSIONS: Although it initially appeared that there is substantial agreement as to which psychoactive substances should be regarded as "hard" and "soft," closer inspection shows that the dividing line is blurred without clear criteria for categorization. At this time, it remains uncertain whether these terms should persist in the scientific literature. We therefore recommend these terms should be avoided or, if used, be clearly and precisely defined.

Schizophrenia causes significant burden to patients' and caregivers' lives.

BACKGROUND: Schizophrenia is a serious public health problem and is ranked among the most disabling diseases in the world. The sub-study presented here was part of a larger project to characterize the burden of schizophrenia on healthcare systems and on individuals living with the disease in Central and Eastern Europe (CEE). AIMS: This sub-study aimed to assess and analyze the impact of schizophrenia on many aspects of the lives of patients and caregivers. METHODS: Psychiatrists from selected centers in seven Central and Eastern European countries were asked to complete a questionnaire in order to collect information about the disease history, characteristics, treatment protocols and resources used for each randomly selected patient. All data were statistically analyzed and compared between countries. RESULTS: Data from 961 patients with schizophrenia (mean age 40.7 years, 45.1% female) were included in the analysis. The mean number of days spent in hospital per patient per year across all seven countries was 25.3 days. Hospitalization occurred on average once per year, with psychiatrist visits 9.4 times per year. Of the patients in the study, 61% were single, 12% divorced and 22% married or cohabiting. Almost 84% were living with relatives or a partner; only 17% lived alone and, on average, 25% of patients received support from social workers. Relatives provided care for approximately 60% of patients and 4% of them had to stop working in order to do so. Twenty-nine percent of the patients were unemployed, and 56% received a disability pension or were retired, with only 19% in full-time employment or education. CONCLUSION: Schizophrenia has a significant effect on the lives of patients and caregivers and impacts their social integration.

Treatment patterns of schizophrenia based on the data from seven Central and Eastern European Countries.

OBJECTIVE: The aim is to analyze how schizophrenia is pharmacologically treated in seven CEE countries: Croatia, Estonia, Hungary, Poland, Serbia, Slovakia and Slovenia. METHODS: Psychiatrists from selected centers in each of participating countries were asked to complete a pre-defined questionnaire on their current clinical practice. Information on protocols and resource utilization in schizophrenia treatment was included and derived from randomly selected patient medical records. Expert opinions on country-wide treatment patterns were additionally sought. This sub-analysis focuses on pharmacological treatment patterns in the last six months and over the course of the disease. RESULTS: 961 patients' data show that during last six months the most commonly prescribed medications were oral atypical antipsychotics: olanzapine (n=268), clozapine (n=234) and risperidone (n=160). The most frequently prescribed atypical antipsychotics over course of disease were: risperidone (54.5%), olanzapine (52.4%) and clozapine (35.1%), along with haloperidol (39.3%). Experts reported risperidone (four countries) and olanzapine (three countries) as first-line treatment, with the same two medications prescribed as second-line treatment. Clozapine was the most reported medication for refractory patients. Approximately 22% of patients received polypharmacy with antipsychotics in at least one period over the disease course. Mean time since diagnosis was 13.1 years and on average 4.8 treatment courses received during that period. Anxiolytics (70%), antidepressants (42%), mood-stabilizers (27%) were also prescribed, with diazepam (35.4%), sertraline (10.5%), valproic acid (17.5%) the most commonly reported, respectively, in each group. The most frequently reported treatment change was switch from one oral atypical antipsychotic to another (51%). CONCLUSION: Oral atypical antipsychotics, mostly older drugs (risperidone, olanzapine, clozapine), were most commonly prescribed for schizophrenia treatment in participating countries. Given that results are from the first large-scale analysis of RWD, we believe these findings can be a benchmark for future real-world studies, which could contribute to the optimization of treatment for this debilitating disease.

Electroconvulsive Therapy Treatment in a Patient With Neurosyphilis and Psychotic Disorder: Case Report and Literature Review.

Syphilis is an infectious disease caused by Treponema pallidum that presents clinically in different ways. Over recent years, an upsurge of new cases of syphilis has been reported, often in combination with human immunodeficiency virus infection. The clinical picture is changing because of the widespread use of antibiotics, and psychiatric manifestations may be the main reason why patients seek medical help. In most cases, treatment with penicillin and psychotropic medication is effective. Electroconvulsive therapy (ECT) is rarely used for the psychiatric manifestations of neurosyphilis: we identified only 19 cases in the literature. We report here on a 40-year-old man newly diagnosed with neurosyphilis during hospitalization for a psychotic state with depression and also review the literature. He was treated with 2 courses of penicillin and several antipsychotics. The ECT was indicated because he failed to respond well to antipsychotic treatment and developed a high risk of dangerous behavior. A series of 8 sessions of ECT rapidly relieved the psychotic symptoms.

Preference for normal, reversed or chimeric self-faces with neutral emotional expression in patients with schizophrenia and control subjects.

OBJECTIVES: Self-face recognition is one of the most distinctive features in human beings. Disturbances of self-face recognition in people with schizophrenia may reflect the underlying neurobiological and psychological factors of the disorder. Our aim was to establish whether differences in preference for the similarity to the true self-face appearance could be found between patients with schizophrenia and a matched control group. SUBJECTS AND METHODS: 14 right-handed patients with schizophrenia and 14 control subjects were enrolled. Subjects were photographed, the pictures were converted to black and white, halved vertically, and four faces were used: normal face (NF), mirrored face (MF), face composed from two left halves of the face (LLF) and from two right halves of face (RRF). Four pairs of faces were exposed to subjects and they chose which they felt was closest to their true appearance. RESULTS: No significant differences for preference were found between the patients and control subjects. Post-hoc analysis of the pooled groups showed a significant difference for preference of NF vs. RRF (20 vs. 8 probands; χ2=5.14, df=1, p<0.05). 18 subjects from the two groups did not change the right-left visual field focus through all four exposures. CONCLUSIONS: The absence of significant differences for preference for true self-image between schizophrenia patients and control subjects might show that self-face recognition is of little importance from the evolutionary perspective. Additional measurements such as eye-tracking control and random multiple projections of the same pairs of faces would contribute to a more thorough interpretation of the findings in future studies of similar design.

Psychopathological characteristics of bipolar and unipolar depression - potential indicators of bipolarity.

BACKGROUND: Establishing whether a depressive episode is part of a unipolar or bipolar disorder is essential for treatment planning. Over recent years, a growing number of publications have discussed psychopathological characteristics that might serve as indicators of bipolarity in patients with a history of depression dominated by unipolar symptoms. Our primary aim was to verify the adequacy of these indicators in contributing to a precise diagnosis in everyday clinical practice. SUBJECTS AND METHODS: We investigated 104 patients diagnosed with major depressive episode at the time of examination. 52 patients had major depressive disorder and 52 patients had bipolar disorder. The patients were then assessed for the presence of potential bipolarity indicators: psychomotor slowing, self-view (self-blaming, feelings of worthlessness), hypersomnia, increased appetite, leaden paralysis/loss of physical energy, weight increase, interpersonal sensitivity, and early morning insomnia, using the Inventory of Depressive Symptomatology. We analysed the correlations between these indicators and the presence of unipolar or bipolar affective disorder. RESULTS: Psychomotor slowing, self-blaming/feelings of worthlessness, increased appetite, leaden paralysis/loss of physical energy, and weight increase were significantly more frequent in bipolar depression than in unipolar depression (p<0.05). Early morning insomnia was significantly more frequent in unipolar depression (p<0.05). There was no statistically significant correlation between hypersomnia or interpersonal sensitivity and either of the affective disorders. CONCLUSIONS: It would be worthwhile identifying the relative importance of clinical indicators for probable BP in large-scale prospective studies. These would contribute to the better diagnostic assessment of major depressive episodes and therapeutic decision-making.

Connections between and within extended psychosis and autistic phenotypes and social relationships in the general population.

OBJECTIVES: Non - clinical individuals with higher levels of autistic traits and psychotic experiences also have problems in social relationships. Therefore, this study aimed to model complex associations between autistic and psychotic phenotypes and indicators of social relationships in the general population using a network approach. METHODS: The sample consisted of 649 participants with a mean age of M = 40.23 and SD = 13.09 sampled from the general population. The sample was representative for the 18-65 years old general population in the Slovak Republic. The following scales were administered: Community Assessment of Psychic Experiences, The Comprehensive Autistic Trait Inventory, and NIH Toolbox Adult Social Relationship Scales. Associations between variables and the presence of communities were identified using Exploratory Graph Analysis. RESULTS: Results revealed four highly stable and densely connected communities within the network: social relationships, autistic traits, positive symptoms, and the last one consisting of all negative symptoms, problems in social interactions, and depression. The most important variables in the network were difficulties in social interaction, perceived rejection, bizarre ideas, depression, and social withdrawal. CONCLUSIONS: The psychotic and autistic phenotypes in the general population showed a network of connections with characteristics of social relationships. Community detection revealed that autistic traits and psychotic-like experiences formed relatively independent communities. Further, there was substantial overlap between negative symptoms (e.g., social withdrawal), and core features of the autistic phenotype, especially social interaction difficulties.

Schizophrenia symptoms and functioning in patients receiving long-term treatment with olanzapine long-acting injection formulation: a pooled analysis.

BACKGROUND: This analysis of pooled data evaluates treatment outcomes of patients with schizophrenia receiving maintenance treatment with olanzapine long-acting injection (OLAI) by means of a categorical approach addressing the symptomatic and functional status of patients at different times. METHODS: Patients were grouped into 5 categories at baseline, 6 months, and 12 months. Shifts between categories were assessed for individual patients and factors associated with improvement were analyzed. 1182 patients from 3 clinical trials were included in the current analysis. RESULTS: At baseline, 434 (36.8%) patients had minimal Positive and Negative Syndrome Scale (PANSS) symptoms but seriously impaired Heinrich Carpenter's Quality of Life Scale (QLS) functioning; 303 (25.6%) had moderate to severe symptoms and seriously impaired function; 208 (17.6%) had mild to moderate symptoms but good functioning, and 162 (13.7%) had minimal symptoms and good functioning. Baseline category was significantly associated with Clinical Global Impression--Severity (CGI-S), extrapyramidal symptoms, working status, age, and number of previous episodes. The majority of all patients starting OLAI treatment maintained or improved (62% at 6 months and 52% at 12 months) their symptom and functioning levels on OLAI maintenance treatment. Less than 8% of the patients showed worsening of symptoms or functioning. An improvement in category was associated with high PANSS positive and low CGI-S scores at baseline. CONCLUSIONS: We present evidence that a composite assessment of schizophrenic patients including symptom severity and functioning is helpful in the evaluation of maintenance treatment outcomes. This approach could also be useful for the assessment of treatment options in clinical practice.The trials from which data are reported here were registered on clinicaltrials.gov as NCT00088491, NCT00088465, and NCT00320489.

Fighting stigma of mental illness in midsize European countries.

PURPOSE: Stigma is the most powerful obstacle to the development of mental health care. Numerous activities aiming to reduce the stigma of mental illness and the consequent negative discrimination of the mentally ill and their families have been conducted in Europe. Descriptions of many of these activities are not easily available, either because there are no publications that describe them, or because descriptions exist only in local languages. This supplement aims to help in overcoming this imbalance by providing a description of anti-stigma activities in 14 countries in Europe regardless of the language in which they were published and regardless whether they were previously published. METHODS: The review was undertaken by experts who were invited to describe anti-stigma activities in the countries in which they reside. It was suggested that they use all the available evidence and that they consult others in their country to obtain a description of anti-stigma activities that is as complete as possible. RESULTS: The anti-stigma activities undertaken in the countries involved are presented in a tabular form. The texts contributed by the authors focus on their perception of the stigma of mental illness and of activities undertaken to combat it in their country. CONCLUSIONS: Although much has been done against the stigmatization and discrimination of the mentally ill, fighting stigma remains an essential task for mental health programs and for society. The descriptions summarized in this volume might serve as an inspiration for anti-stigma work and as an indication of potential collaborators in anti-stigma programs.

Analysis of Motives and Factors Connected to Suicidal Behavior in Patients Hospitalized in a Psychiatric Department.

(1) Background: This study aimed to investigate the motives and factors connected to suicidal behavior in 121 hospitalized patients with intentional self-harm (diagnosis X 60-81 according to the ICD-10); (2) Methods: Suicidal behavior of the patient was assessed from data obtained by psychiatric examinations and by the Columbia Suicide Severity Rating Scale. Analysis of data to identify the patients' reason and motives behind suicidal behavior in a group of patients with a suicide attempt (SA, n = 80) and patients with Non-Suicidal Self-Injurious Behavior (NSSIB, n = 41) was carried out; (3) Results: Results showed that patients with affective disorder have a 19-times higher rate of SA against other diagnoses. Patients with personality disorders have a 32-times higher rate of NSSIB than patients with other diagnoses. Living alone and the absence of social support increased the likelihood of SA. Qualitative data analysis of patients' statements showed different themes in the justification of motives for suicidal behavior between SA and NSSIB cases. Significant differences were shown for non-communicated reasons, loneliness, social problems, extortion, and distress; (4) Conclusions: The evaluation of patients' verbal statements by qualitative analysis during the psychiatric examination should be considered in clinical practice. It should be considered to include self-poisoning in the criteria of the Non-suicidal Self-Injury diagnostic categories.

The role of the vagus nerve in depression.

The etiopathogenesis of depression is a highly complex process characterized by several neurobiological alterations including decreased monoamine neurotransmission in the brain, dysregulated hypothalamic-pituitary-adrenal axis activity, decreased neuronal plasticity, and chronic inflammation in the brain and peripheral tissues. Experimental and clinical studies indicate that the vagus nerve may influence these processes. The importance of the vagus nerve in the etiopathogenesis of depression is further supported by its involvement in the induction of sickness behavior, as well as by clinical studies confirming a beneficial effect of vagus nerve stimulation in depressed patients. The aim of this article is to describe current knowledge of afferent and efferent vagal pathways role in the development and progression of depression.

The vagus nerve role in antidepressants action: Efferent vagal pathways participate in peripheral anti-inflammatory effect of fluoxetine.

The mechanisms responsible for the anti-inflammatory effects of antidepressants are only partially understood. Published data indicate that the vagal anti-inflammatory pathway could be involved in mediating this effect. Therefore, we investigated the influence of subdiaphragmatic vagotomy on the anti-inflammatory effect of fluoxetine in rats injected with lipopolysaccharide (LPS) to induce an inflammatory response. The extent of this response was determined by measurement of TNF-α, IL-1ß, and IL-6 plasma levels, along with gene expression of TNF-α, IL-1ß, and IL-6 in the spleen and selected structures of the brain. To evaluate possible central mechanisms, c-fos mRNA levels were determined in the nucleus of the solitary tract, dorsal motor nucleus of the vagus, paraventricular hypothalamic nucleus, basolateral amygdala, central nucleus of the amygdala, hippocampus, and frontal cortex. We found that pretreatment with fluoxetine substantially prevented LPS-induced increases of pro-inflammatory cytokines in plasma and gene expression in the spleen and brain in animals with an intact vagus nerve. However, in vagotomized animals, fluoxetine pretreatment only partially attenuated the LPS-induced increase in these markers of peripheral inflammation. Our data has shown that fluoxetine exerts potent anti-inflammatory effects in both the periphery and brain. Moreover, we found that the peripheral anti-inflammatory action of fluoxetine is mediated, at least partially, by activation of a vagal anti-inflammatory pathway. The role of the vagus nerve in mediating the anti-inflammatory effects of antidepressants has been marginally explored and our findings highlight its potential contribution to this mechanism of action of antidepressants.

c-Fos expression response to olanzapine, amisulpride, aripiprazole, and quetiapine single administration in the rat forebrain: Effect of a mild stress preconditioning.

Antipsychotics have been shown to stimulate different forebrain areas, whereas some of them are sensitive to stress. In the present study, effect of a single administration of olanzapine (OLA), amisulpride (AMI), aripiprazole (ARI), and quetiapine (QUE) on the activity of cells in the striatal dorsolateral (stDL) area, the periventricular zone (peVZ), the septal ventrolateral (seVL) nucleus, and the accumbens nucleus shell (shACC) and core (coACC) was investigated in male rats preconditioned with a mild stress complex (CMS) for 20 days. The objective of the study was to extend the anatomical-functional knowledge on the mechanism of selected antipsychotics with the goals: 1) to analyze the ability of the selected antipsychotics to induce c-Fos protein expression in the above mentioned forebrain structures and to map the pattern of their topography and 2) to find out whether longer-lasting mild stress preconditioning may modify the impact of the selected antipsychotics on the activity of cells in the forebrain areas in adult rats. Ten groups of rats were used. CMS complex contained five stressors: cage crowding, air-puff noising, wet bedding, predator stress, and forced swimming. AMI (20 mg/kg), OLA (5 mg/kg), QUE (15 mg/kg), and ARI (10 mg/kg/b.w.) were administered intraperitoneally and 90 min later the animals transcardially perfused by fixative. c-Fos was visualized by ABC complex. In unstressed animals, OLA and ARI elevated c-Fos expression in all areas studied, AMI and QUE in all areas except stDL, seVL and coACC, shACC FL-2 (shACC posterior level), respectively. CMS potentiated the effect of AMI in coACC, and QUE in shACC FL-2 and suppressed the effect of AMI in peVZ, and ARI in peVZ and seVL. The present data provide new insights into activity of cells in response to CMS challenge, which might be helpful in understanding the diverse clinical effects of atypical antipsychotics.

Relapse prevention in schizophrenia: evidence from longterm, randomized, double-blind clinical trials.

Fourteen long-term (duration at least 26 months) double-blind, randomized studies comparing second-generation antipsychotics (SGAs) with placebo, conventional antipsychotics, or two or more SGAs, published after 2002 have been reviewed and are summarized in this chapter. Methodological problems and factors influencing results such as patient populations involved, outcome criteria, and dosages of evaluated drugs are discussed.

Effects of atypical and typical antipsychotic treatments on sexual function in patients with schizophrenia: 12-month results from the Intercontinental Schizophrenia Outpatient Health Outcomes (IC-SOHO) study.

PURPOSE: Sexual dysfunction in patients with schizophrenia can reduce quality of life and treatment compliance. This report will compare the effects of selected atypical and typical antipsychotics on sexual function in a large, international population of outpatients with schizophrenia who were treated over 1 year. SUBJECTS AND METHODS: Outpatients with schizophrenia, who initiated or changed antipsychotic treatment, and entered this 3-year, prospective, observational study were classified according to the monotherapy prescribed at baseline: olanzapine (N=2638), risperidone (N=860), quetiapine (N=142) or haloperidol (N=188). RESULTS: Based on patient perception, the odds of experiencing sexual dysfunction during 1 year of therapy was significantly lower for patients treated with olanzapine and quetiapine when compared to patients who received risperidone or haloperidol (all P< or =0.001). Females on olanzapine (14%) or quetiapine (8%) experienced a lower rate of menstrual irregularities, compared to females on risperidone (23%) or haloperidol (29%). Significant discordance was evident between patient reports and psychiatrist perception of sexual dysfunction, with psychiatrists underestimating sexual dysfunction (P< or =0.001). CONCLUSION: These findings indicate clinically relevant differences exist in the sexual side effect profiles of these selected antipsychotics. These factors should be considered when selecting the most appropriate treatment for outpatients with schizophrenia.