Metabolic syndrome - a significant risk factor for cardiovascular morbidity and mortality - is twice as prevalent among psychiatric patients (21-63%) as general populations (20-24%). Although there is an inherent illness-associated metabolic risk, medications do contribute. Atypicals vary in metabolic risk from high (clozapine, olanzapine), moderate (risperidone, quetiapine) to low (aripiprazole, ziprasidone) (ADA, 2004). Few studies have comprehensively measured cardiovascular risk or directly compared antipsychotics. Limited controlled data show that antipsychotic-induced metabolic abnormalities may be reversible, rationalizing the switch to a lower-risk agent (DeNayer, 2004). Non-HDL-cholesterol encompasses all atherogenic cholesterols and provides a marker of CV risk: an increase of 29ng/dL in diabetics is associated with 50% increased risk (Jiang, 2004). Non-HDL-cholesterol is independently associated with increased risk of non-fatal myocardial infarction and angina.

This study will provide cross-European data from 13 countries on MS rates in schizophrenia and will assess antipsychotic metabolic profiles and benefits of antipsychotic switching.

In this ongoing, 16-week, open-label, European multicentre study, 258 schizophrenia patients treated for ≥3 months with olanzapine, risperidone or quetiapine and who have MS will be randomized to switch to aripiprazole (Week 1: 5mg/day; Week 2: 10mg/day; flexible 10-30mg/day after Week 2) or continue with previous antipsychotic. the primary objective is to demonstrate superiority of aripiprazole versus atypicals on mean percentage change of fasting non-HDL-cholesterol from baseline to Week 16.

This study will provide the first direct and comprehensive comparison of metabolic risk with various atypicals in Europe and should impact the future management of schizophrenia.

This study investigated the association between an enlarged set of SNPs at Heat shock proteins (HSPs) 70 gene and schizophrenia.

Two hundred and ninety four patients with schizophrenia and 287 controls were enrolled in the study. Genotypings of 5 SNPs of HSP70 were performed using pyrosequencing method.

Significant association was detected at rs2075799 (allele A, Chi suare =8.03, d.f.=1 p=0.0046), but not at rs2227956 (p=0.28), rs1043618 (p=0.88), rs562047 (p=0.47) or rs539689 (p=0.32). in fact, the rs2075799*G/A genotype was more represented in patients with schizophrenia than in controls (Chi-sq=8.23, d.f.=1, p=0.0041). Haplotype based associations were also detected (global p value 0.000003); the T-A-C-C-G haplotype was more prevalent among the patients (odds ratio, OR 5.95). Sliding windows analysis revealed a major contribution from rs2227956 and rs2075799 (global-p value 0.0075), with T-A haplotype significantly associated with schizophrenia. There was no evidence of an association between the clinical variables and schizophrenia across the genotypes.

Our results raise the possibility that HSP70 gene (i.e., haplotypes of rs2075799) might be implicated in the development of schizophrenia, although limited by rare haplotypic association with the disease. Hence further studies from different ethnics should be performed to confirm these results.

Life expectancy for individuals with schizophrenia is 20% lower than in general population. Medical illnesses, psychiatric comorbidities, less access to care, poverty and limited perception of illness are some of the most important factors associated with increased risk of morbidity. Cardiovascular death (CVD) is a major contributor to increased mortality in schizophrenia 2,3. Prevalence of obesity in patients with schizophrenia (40%-60%) is twice the rate of the general population (20%-30%). Obesity, high abdominal perimeter, serum lipid levels, and smoking are significant, Independent Risk Factors for CVD.

Metabolic syndrome is a cluster of metabolic disturbances, which is associated with an increased risk of CVD.

To estimate the prevalence of CVRF in schizophrenic outpatients treated at Granollers' CSM.

Cross-sectional descriptive study about 100 schizophrenic outpatients treated at CSM Granollers. Data on sociodemographics, physical examinations, blood test parameters, CVRF history and treatments are recorded. Each CVRF is established according to international criteria and/or pharmacological treatment.

Secondary objectives:

• • Prevalence of Metabolic Syndrome;

• • Antipsychotic drugs treatment.

• • Physical examination;

• • Lab parameters;

• • Other CV risk factors (smoking, alcohol intake…).

Estimated prevalences for most of the CVRF in schizophrenic outpatients are, in general, higher than those expected of the same age group in the general population. Data presented can support therapeutic decision-making and suggests a need of new prevention and monitoring strategies. New guidelines for monitoring and intervention will be needed for monitoring and intervention.

Unemployment is a factor that negatively affects the health of the entire population and is an important cause of exclusion, affecting persons with severe mental health problems. the rise of unemployment rates for these persons contrasts with the dropping of unemployment rate for the general population. Schizophrenia is associated with long-term unemployment. Cognitive dysfunction, rather than clinical symptoms, may be the most important factor in the ability to work for patients with this disorder.

This study aims to evaluate the relationship between clinical symptoms, cognitive functioning and employment status in patients with schizophrenia.

40 patients with schizophrenia were evaluated with PANSS, CANTAB (Cambridge Neuropsychological Test Automated Battery) and with an interview regarding work experience.

The results suggest that poor premorbid function, negative symptoms and cognitive dysfunction are significantly associated with unemployment in schizophrenia.

The results of this study confirm the importance of cognitive functioning as a predictor of work function in patients with schizophrenia and the need of cognitive rehabilitation programs.

To examine the efficacy of second-generation-antipsychotics (SGAs) in the treatment of negative symptoms in Schizophrenia.

Two meta-analyses were carried out using placebo or haloperidol as comparators. Studies were identified by searching for randomized, double-blind, placebo and/or haloperidol -controlled trials reporting data on efficacy of SGAs. Search was extended to the following databases: Pubmed, the Cochrane Central Register of Controlled Trials, Proquest Health and Medical Complete, Science Citation Index Expanded, and Current Contents Connect. the outcome measure used was the change in negative symptoms, choosing a standardized statistic (Cohen's d) to synthesize data.

A total of 46 homogeneous trials (Q=45.18, df=50, p=0.667, I2=0%) were included. in the placebo-controlled meta-analysis, the effect sizes (Cohen's d) obtained for amisulpride, haloperidol, olanzapine, quetiapine, risperidone and ziprasidone were 0.52, 0.34, 0.43, 0.36, 0.40 and 0.46, respectively, favoring active treatment against placebo (p< 0.001 in all cases). Comparing SGAs against haloperidol, showed just a statistically significant trend favoring SGA's in treatment of negative symptoms (Cohen's d = 0.15, p=0.008). Comparisons by drug showed a significant low and low-to-moderate standardized mean favoring SGA: Cohen's d = 0.34, p< 0.001; Cohen's d = 0.27, p< 0.001 and Cohen's d = 0.19, p=0.030, respectively for ziprasidone, risperidone and olanzapine.

Most antipsychotics (aminosulpride, haloperidol, olanzapine. quetiapine, risperidone, ziprasidone) are effective in treatment of negative symptoms, showing moderate effect sizes. Amisulpride and ziprasidone were slightly better than the rest of drugs when compared with placebo. Compared with haloperidol, SGA showed controversial results.

The DSM-IV-TR category “brief psychotic disorder” includes different concepts that have been defined before like bouffée délirante, cycloid psychosis and “acute and transient psychosis” in the last ICD-10. Limited prospective studies have been done, and they all show a marked diagnostic instability during follow-up. According to that, its independent nosologic entity is still uncertain.

To determine the diagnostic stability of the brief psychotic disorders as well as their distinct clinical features.

Observational, retrospective, longitudinal study of 80 consecutive patients admitted at the acute psychiatric inpatient service of a general hospital between 2000 and 2006. at discharge, all of them fulfilled diagnostic criteria for “brief psychotic disorder” according to DSM-IV. Demographic and psychopathological data were analysed.

Mean age (SD) was 31.3 (9.5), most of them women (63%). the most frequent previous stressor was related to labour, while up to 45% didn't report any. 51% had no psychiatric family history. 15 (19%) patients previously had a brief psychotic episode. Psychopathological disturbances identified were: thought disorder 69%, anxiety 66.6%, insomnia 57.7%, suspiciousness 53.5%, rapidly changing delusions 53.3% (paranoid contents 75.3%), perplexity 46.5%, auditory hallucinations 45.1%, mood lability 36.6%, elation 23.9%, depressed mood 22.5% and irritability 12.7%. in the 24 month follow-up, 32.5% changed diagnosis to schizophrenia, 3"9% to schizoaffective, 10% to bipolar disorder and 16.9% achieved clinical remission. 28.5% were lost to follow-up.

“Brief psychotic disorder” category is still uncertain and more data may be necessary to clarify if it should remain as a distinct nosologic entity.

Research in social cognition has shown that subjects affected by schizophrenia are impaired in understanding other people mental state named “Theory of Mind” and in many other social cognition tasks. It is possible to apply qualitative analysis to examine their errors in different social cognition tasks. Typically they fail in perspective taking, in adherence to the context and in emotional contagion (the tendency to express and feel emotions that are similar to and influenced by those of others). the aim of our study was to examine the different answers of schizophrenic subjects in social cognition tasks and apply a model of path analysis on their errors in these tasks.

We assessed multiple dimension of social cognition in 210 schizophrenic patients and 200 healthy controls, matched for age and gender, with emotion recognition task, false beliefs task and social knowledge task. to control for modulating effects of symptoms and cognitive deficits, clinical scales and a neuropsychological test battery were employed. All patients were recruited from the psychiatric service San Salvator Hospital in L'Aquila (Italy).

Schizophrenic patients showed significantly lower scores, errors in perspective taking (p< 0.001), in emotional contagion (p=0.001) and adherence to the context (p=0.001). Results in the domains of perspective taking and emotion contagion were not explained by symptoms, duration of illness or neurocognition deficits.

Our findings are in line with previous reports on theory of mind deficits in schizophrenia, as measured by a variety of paradigms, and may suggest deficits in all social cognition domains.

Patients who seek treatment often suffer from negative auditory vocal hallucinations (‘voices’). However, some of these patients also report positive or useful voices, that they wish to preserve. When this wish is neglected by their therapist, this may lead to rejection of therapy or low compliance. This study describes prevalence, characteristics, course of and attributions to these voices in psychotic and non-psychotic patients.

One hundred and thirty one patients of a Voices Clinic and 65 members of the Dutch Resonance Foundation were assessed with the Positive and Useful Voices Inquiry. Data were analyzed using Pearson's chi-square, one-way ANOVA, Student's T-test and Crohnbach's alpha statistics.

First voices are most often reported as negative. the lifetime prevalence of positive voices ranged from 50 to 75%, useful voices were reported by 40 to 60% of respondents, with higher prevalences among the members of the Resonance Foundation. Positive voices occur more among non-psychotic patients. No significant association was found between voice characteristics and diagnosis. Attributions of protective power to positive voices has the strongest association with positive experience. Useful voices that are advising are experienced as most useful. Over 30% of respondents want to keep their positive and/or useful hallucinations. This wish is significantly associated with perceived control over the voices.

The prevalence of positive and useful voices is considerable and therefore clinically relevant. A substantial part of patients want to preserve these voices.

We aimed to identify best predictors of cognitive and functional disability in chronic schizophrenia over time.

We examined 95 hospitalised patients with schizophrenia (DSM-IV criteria) in a long stage unit and 53 healthy controls (matched for age, gender, and years of education). Neuropsychological assessment included tests for Verbal Memory, Working Memory, Executive Functioning and Processing Speed. Functional Disability was assessed with the Disability Assessment Schedule (DAS-WHO) both at baseline and 6 months after.

As expected, patients" performance was significantly lower than healthy comparison subjects on all neurocognitive variables at baseline. Most, but not all, neurocognitive measures were positively correlated with the Functional Disability domains at follow up, including Self Care Management, Vocational Outcome, Family Contact and Social Competence. Results of mediation analyses suggest that all significant relationships identified between cognitive measures and functional outcome were significantly mediated by the Index Processing Speed (PS) with various effects ((between p < 0.05 for PS (z = -2.06) and p < 0.01 for PS (z = -3.01)).

Our data show that Processing Speed plays a determinant role in the relationship among neurocognitive symptoms and Self Care, Vocational Outcome and Social Competence. the model emphasizes the role of PS as the best longitudinal predictor of the level of autonomy in chronic patients with schizophrenia. PS acts as a pathway through which VM, EF and WM predict the course of patients’ functional ability over time.

To examine the relative contributions of psychiatric symptoms, functional disability, neuropsychological functioning and sociodemographic variables to quality of life (QOL) in patients with chronic schizophrenia.

We examined 165 hospitalised patients with long term schizophrenia (DSM-IV). Measures of psychiatric symptoms included depression (Calgary depression Scale), insight (David Insight Scale), symptom severity (BPRS) and PANSS (Positive and Negative Symptom Scale). Neuropsychological battery included tests for verbal memory, executive functioning, verbal fluency, working memory, motor speed and processing speed. Functional disability was assessed with the Disability Assessment Schedule (DAS-WHO) and Quality of life was assessed with the Quality of Life Scale.

Age, years of evolution, negative symptoms, insight and neuropsychological variables (except motor speed) all were significantly related to level of quality of life. in a multiple regression analysis, entering the neuropsychological functioning, functional disability and negative symptoms generated a model which accounted for a 74.9% of the variance in QOL. Functional disability, as expected, accounted for 56% of the variance, whereas Processing Speed explained an additional 6.2%. Symptom Severity and Verbal Fluency predicted 3.7% and 3.5% of the variance, respectively. Negative symptoms, Verbal Memory and Vocabulary, were also significant predictors in the model, but had less predictive value. However, Positive Symptoms and Sociodemographic Variables did not significantly contribute to predict quality of life.

Our findings support the predictive value of neuropsychological functioning, functional disability and severity of negative symptoms in long term quality of life in schizophrenia.

To explore tolerability, safety and efficacy of flexible doses of oral paliperidone ER in adult non-acute patients with schizophrenia requiring a change in their medication due to lack of efficacy with their previous oral antipsychotic.

Interim analysis of a prospective 6-month, open-label, international study. Patients completing the first 3 months of this study were analyzed. Endpoints were the change in the Positive and Negative Syndrome Scale (PANSS) from baseline to endpoint, Clinical Global Impression-Severity Scale (CGI-S), weight change and adverse events (AEs).

81 patients were included (57% male, mean age 41.3±13.6 years, 85% paranoid schizophrenia). 89% of the 81 patients completed the first 3 months of the study. Reasons for early discontinuation were lack of efficacy (3.7%), subject choice (2.5%), loss to follow-up (2.5%) and AE (1.2%). the mean mode dose of paliperidone ER was 6 mg/day. Mean total PANSS decreased from 82.8±16.0 at baseline to 69.2±19.1 at endpoint (mean change -13.6±15.6; 95% confidence interval [CI]-17.0;-10.1, p< 0.0001). the percentage of patients rated mildly ill or less in CGI-S increased from 19.8% to 49.4%. AEs reported in ≥3% were insomnia (4.9%), somnolence (4.9%), extrapyramidal disorder (3.7%), restlessness (3.7%) and psychotic disorder (3.7%). Mean weight change from baseline to endpoint was 0.34 kg (95%CI -0.35;1.03, p=0.71).

These interim open-label data support results from recent randomized controlled studies that flexibly dosed paliperidone ER is safe, well tolerated and effective in patients with schizophrenia requiring a change in medication due to lack of efficacy with their previous oral antipsychotic treatment.

To explore tolerability, safety and treatment response of flexible doses of oral paliperidone ER in patients with schizophrenia suffering from an acute episode.

Interim analysis of a 6-week prospective, open-label, international study. Endpoints were the rate of responders defined as a ≥30% improvement in the Positive and Negative Syndrome Scale (PANSS) from baseline to endpoint, the Clinical Global Impression-Severity Scale (CGI-S), weight change and adverse events (AEs).

100 patients were analyzed (51% male, mean age 39.0±11.6 years). 82% of patients completed the study. Most frequent reasons for early discontinuation were subject choice (10%) and lack of efficacy (7%). the mean dose of paliperidone ER was 5.9 mg/day at baseline and 7.9 mg/day at endpoint. an improvement of ≥30% in total PANSS was observed in 68% of patients (95% confidence interval [CI]58%;77%], with a decrease in mean total PANSS scores from 98.2±16.2 at baseline to 71.1±20.3 at endpoint (mean change -27.1±19.9; 95%CI -31.1;-23.2, p< 0.0001) and onset of efficacy as of day 2. the percentage of patients rated as at least markedly ill in CGI-S decreased from 69% to 20.3%. AEs reported in ≥5% were insomnia (14%), tachycardia (10%), akathisia (6%), extrapyramidal disorder (6%), headache (5%) and schizophrenia (5%). Median weight gain was 0.7 kg (95% CI 0.19;1.96) from baseline to endpoint.

This analysis supports data from recent controlled studies that flexibly dosed paliperidone ER is safe, well tolerated and associated with a clinically meaningful treatment response in patients with an acute schizophrenic episode.

Outcome measures in schizophrenia are defining aspects for deciding the status of recovery based upon which people’ scientific body forms opinions. It is also important in dealing with stigma related to schizophrenia. Recently the concept of ‘recovery’ and ’ outcome’ has come under scientific scrutiny. Literature does not show a consistent pattern in outcome. both short term and long-term outcome show variability, which is often, explained by cultural factors. It has been generally considered that devolved countries have poor outcome than developing, non-industrialized countries. This view has also been challenged recently. the paper draws from the conceptual aspects if our outcome measure are capturing ‘real-life’ situation. We conducted two studies in Mumbai, India:

1. 1. Study of stigma & discrimination, which brought out the facts of families’ expectation and disappointments with level of recovery.

2. 2. A 10 years long term study, to determine recovery status of recovered patients.

80% patients and families felt that recovery is inadequate and short of social integration despite continued treatment in stigma study. in outcome study, 60% patients showed good recovery as per CGIS. These patients were reassessed on 13 outcome criteria's of Meltzer. It is observed tat half of the patients who recovered continue to live with symptoms, a quarter with varying suicidality and side effects, most of the patients were not socially integrated, majority have not returned to productivity, employment and education It is concluded that outcome criteria's need a thoughtful revision and a new perspective to capture ground reality.

Schizophrenia is highly familial neuropsychiatric disorder with heritability estimated at 60-90%. Even unaffected first-degree relatives of schizophrenia manifested some neuropsychological abnormalities as well as neurologic soft sign and morphologic anomalies. the aim of this study was to evaluate personality profile in first-degree relatives of schizophrenia compared to their schizophrenia probands and healthy controls and whether personality profile might be endophenotype of schizophrenia.

The subjects were 97 first-degree relatives of schizophrenia, 48 their schizophrenia probands, and 106 healthy controls, who completed Temperament and Character Inventory (TCI) scale. Relatives were further divided into presumed carriers and pesumed non-carriers by schizophrenia genetic loading. Group difference in TCI scores were compared by general linear model using age and gender as covariates.

1. 1. There were significant group differences in HA scores between healthy controls, relatives, and probands after controlling age and gender, in that HA scores were increased by healthy controls, relatives, and probands in order.

2. 2. Presumed carriers have higher HA scores than presumed non-carriers and healthy controls.

3. 3. Proband group showed significantly lower RD and lower P in temperament dimension and lower SD, lower C, and higher ST in character dimension compared to other groups.

We found that HA scores of first-degree relatives of schizophrenia is intermediate level between schizophrenia probands and healthy controls. Considering increase of HA with schizophrenia genetic loading, HA may be potential endophenotype of schizophrenia. Further research with longitudinal follow up is needed to elucidate the clinical implication of high HA observed in schizophrenia family.

Patients with schizophrenia have high rates of mortality, despite improvement in health care. Acute admission can be an excellent target for the screening of acute and chronic disorders in these patients. to our knowledge no study has been performed clarifying which blood analysis should be requested to patients with schizophrenia upon an acute admission. the aim of the present study is to clarify which blood analysis should be requested to these patients, when acutely admitted.

A case-control study was performed, comparing blood analyses in patients with schizophrenia and schizoaffective disorder upon their admission, with subjects without schizophrenia from the general population.

We found a significantly higher number of patients with changes on leukocytes, glucose, and AST values, and a significantly lower number with higher cholesterol (total and LDL), creatinine, ALP, and albumin. Many patients presented low values of hemoglobin, erythrocytes, platelets, glucose, vitamin B12, albumin, and HDL-cholesterol, and high values of CK, blood electrolytes, and CRP.

Present data clearly support the routine requisition of full blood count, CRP, CK, glucose and AST on admission. Although the evidence is less robust, it seems reasonable to request electrolytes, albumin and vitamin B12. NCEP laboratorial parameters may be should not be requested by routine in this context, as it tends to underestimate metabolic syndrome. the present work does not find evidence for routine requisition of urea, folic acid, and VDRL. Blood phosphorus, calcium and thyroid hormones need further investigation.