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Summary Background Many people with schizophrenia experience stigma caused by other people's knowledge, attitudes, and behaviour; this can lead to impoverishment, social marginalisation, and low quality of life. We aimed to describe the nature, direction, and severity of anticipated and experienced discrimination reported by people with schizophrenia. Methods We did a cross-sectional survey in 27 countries, in centres affiliated to the INDIGO Research Network, by use of face-to-face interviews with 732 participants with schizophrenia. Discrimination was measured with the newly validated discrimination and stigma scale (DISC), which produces three subscores: positive experienced discrimination; negative experienced discrimination; and anticipated discrimination. Findings Negative discrimination was experienced by 344 (47%) of 729 participants in making or keeping friends, by 315 (43%) of 728 from family members, by 209 (29%) of 724 in finding a job, 215 (29%) of 730 in keeping a job, and by 196 (27%) of 724 in intimate or sexual relationships. Positive experienced discrimination was rare. Anticipated discrimination affected 469 (64%) in applying for work, training, or education and 402 (55%) looking for a close relationship; 526 (72%) felt the need to conceal their diagnosis. Over a third of participants anticipated discrimination for job seeking and close personal relationships when no discrimination was experienced. Interpretation Rates of both anticipated and experienced discrimination are consistently high across countries among people with mental illness. Measures such as disability discrimination laws might, therefore, not be effective without interventions to improve self-esteem of people with mental illness. Funding South London and Maudsley NHS Foundation Trustees, UK Department of Health SHiFT programme, German Ministry of Education and Research.

Medical decisions have to rely on evidence-based medicine. However, evidence is not a clearly defined term. Several evidence criteria have been proposed, yet statistical meta-analyses are considered to be core criterion of empirical studies in that they combine single evidence from different studies into an encompassing conclusion. We argue however that meta-analyses have major limitations in this context. Five arguments are presented: (1) the nature of a study design affects the results and thus comprehensive meta-analyses covering studies with different designs are not informative; (2) combining different studies into a meta-analysis is methodologically not informative; (3) meta-analyses consider the variance between studies not as informative but as random noise; (4) the strategy to identify informative studies is a decisive determinant of meta-analyses; and (5) the value of conclusions from meta-analyses depends on the choice of statistics chosen as combined results from the various single studies. Instead, meta-analyses are useful tools for generating hypotheses in a posteriori analysis.

Objective: To assess the efficacy of the new atypical antipsychotic drug, amisulpride. Method: Studies comparing the efficacy of amisulpride with that of haloperidol and risperidone, respectively, are reviewed. Outcome measures were Clinical Global Impression, Brief Psychiatric Rating Scale (BPRS), and Positive And Negative Symptom Scale (PANSS) scores. Results: Amisulpride was at least as effective as haloperidol and risperidone in the improvement of positive symptoms, and significantly more efficacious than haloperidol in reducing PANSS negative subscores (P=0.038) in patients with acute exacerbations. Amisulpride demonstrated a greater improvement in BPRS total scores (P

Nowadays, Selective Serotonin Reuptake Inhibitors (SSRI) are well established in psychopharmacological therapy. They have been shown to be very effective and having a favourable side effect profile. However, bleeding events are rare but there may be potentially severe complications under treatment with SSRI. These complications can occur under SSRI alone and in combination with anticoagulative drugs, whereas the coagulation parameters can remain unchanged. Pathophysiologically these bleeding complications are related to a reduced concentration of serotonin in the blood and platelets. Reduction of serotonin, which occurs under treatment with SSRI, can lead to disturbances of platelet function and may also activate the fibrinolytic system. Both effects increase the risk of bleeding complications. In combination with anticoagulants, besides the serotonin-related bleeding events, additionally influences of SSRI on metabolism of the anticoagulative drugs due to their interactions with the Zytochrom-P450 system and changes of free plasma levels of the anticoagulative drugs, caused by a displacement from the plasma proteins through the SSRI, must be taken into consideration.

Evaluation of influence of psychopathological symptoms (AMDP System) and diagnosis (ICD-9) on the choice of drug therapy (neuroleptics or antidepressants) for psychiatric in-patients was the aim of this work. Statistical analysis of 3745 patients led to three different decision-making procedures. These procedures are based on symptoms or diagnoses alone or on both symptoms and diagnosis. CART-Analysis was used for statistical analysis. Reclassification errors for neuroleptics were always larger than reclassification errors for antidepressants. The results show that both symptoms (error neuroleptics 20.2%, respectively antidepressants 15.0%) and diagnosis (20.8%, resp. 11.9%) alone are not sufficient to explain the choice of drug therapy. Lowest error rates were gained in a hierarchical model for the choice of drug treatment where both diagnosis and symptoms were used (17.1%, resp. 10.1%).

PURPOSE To detect regional differences in accompanying metabolic changes, 1H-Magnetic Resonance Spectroscopic Imaging (MRSI) was performed in 16 patients with Alzheimer's disease (AD); the clinical diagnosis was based upon DSM-III-R and NINCDS-ADRDA guidelines. METHODS In the hippocampal region metabolic maps of the local distribution of N-acetylaspartate (NAA), choline (Cho), creatine compounds (P(Cr)) and lactate were determined. Ratios of Cho/NAA, (P)Cr/NAA and Cho/(P)Cr calculated from selected hippocampal spectra were compared to those from healthy volunteers (n = 17). RESULTS AD patients demonstrated an increase of Cho/NAA and (P)Cr/NAA ratios caused by increased choline compounds and decreased NAA. These alterations were observed in 11/12 cases in the hippocampal and in 7/12 in the temporo-occipital region. Hippocampal Cho/NAA ratios (0.56 +/- 0.19) were significantly elevated compared with controls (0.33 +/- 0.04; p < 0.0001). CONCLUSION The observed elevation of choline compounds in the hippocampus supports the hypothesis that alterations in the cholinergic system play an important role in Alzheimer's disease. The observed reduction of NAA is due to neuronal degeneration.

The aim of this study was to evaluate the level of anticipated discrimination in people with schizophrenia (n = 732) from 27 countries in the International Study of Discrimination and Stigma Outcomes (INDIGO).Anticipated discrimination was assessed through four questions of Discrimination and Stigma Scale. Twenty-five individuals were identified at each site who were reasonably representative of all such treated cases within the local area.Sixty-four per cent of the participants reported that they had stopped themselves from applying for work, training or education because of anticipated discrimination. Seventy-two per cent of them reported that they felt the need to conceal their diagnosis. Expecting to be avoided by others who know about their diagnosis was highly associated with decisions to conceal their diagnosis. Those who concealed their diagnosis were younger and more educated. The participants who perceived discrimination by others were more likely to stop themselves from looking for a close relationship. Anticipated discrimination in finding and keeping work was more common in the absence than in the presence of experienced discrimination, and the similar findings applied to intimate relationships.This study shows that anticipated discrimination among people with schizophrenia is common, but is not necessarily associated with experienced discrimination.

We report on the results of controlled clinical antidepressant trials with elderly depressed patients which meet certain methodological requirements and have been published since 1980. The safety, tolerability, and efficacy of the investigated compounds are reviewed. In the light of the diagnostic problems and the altered pharmacokinetic behavior in this special age group we conclude that the progress in scientific knowledge in the last 13 years has only been moderate.

Deletions within the neurexin 1 gene (NRXN1; 2p16.3) are associated with autism and have also been reported in two families with schizophrenia. We examined NRXN1, and the closely related NRXN2 and NRXN3 genes, for copy number variants (CNVs) in 2977 schizophrenia patients and 33 746 controls from seven European populations (Iceland, Finland, Norway, Germany, The Netherlands, Italy and UK) using microarray data. We found 66 deletions and 5 duplications in NRXN1, including a de novo deletion: 12 deletions and 2 duplications occurred in schizophrenia cases (0.47%) compared to 49 and 3 (0.15%) in controls. There was no common breakpoint and the CNVs varied from 18 to 420 kb. No CNVs were found in NRXN2 or NRXN3. We performed a Cochran-Mantel-Haenszel exact test to estimate association between all CNVs and schizophrenia (P = 0.13; OR = 1.73; 95% CI 0.81-3.50). Because the penetrance of NRXN1 CNVs may vary according to the level of functional impact on the gene, we next restricted the association analysis to CNVs that disrupt exons (0.24% of cases and 0.015% of controls). These were significantly associated with a high odds ratio (P = 0.0027; OR 8.97, 95% CI 1.8-51.9). We conclude that NRXN1 deletions affecting exons confer risk of schizophrenia. © The Author 2008. Published by Oxford University Press. All rights reserved., link_to_OA_fulltext

Reduced fecundity, associated with severe mental disorders, places negative selection pressure on risk alleles and may explain, in part, why common variants have not been found that confer risk of disorders such as autism, schizophrenia and mental retardation. Thus, rare variants may account for a larger fraction of the overall genetic risk than previously assumed. In contrast to rare single nucleotide mutations, rare copy number variations (CNVs) can be detected using genome-wide single nucleotide polymorphism arrays. This has led to the identification of CNVs associated with mental retardation and autism. In a genome-wide search for CNVs associating with schizophrenia, we used a population-based sample to identify de novo CNVs by analysing 9,878 transmissions from parents to offspring. The 66 de novo CNVs identified were tested for association in a sample of 1,433 schizophrenia cases and 33,250 controls. Three deletions at 1q21.1, 15q11.2 and 15q13.3 showing nominal association with schizophrenia in the first sample (phase I) were followed up in a second sample of 3,285 cases and 7,951 controls (phase II). All three deletions significantly associate with schizophrenia and related psychoses in the combined sample. The identification of these rare, recurrent risk variants, having occurred independently in multiple founders and being subject to negative selection, is important in itself. CNV analysis may also point the way to the identification of additional and more prevalent risk variants in genes and pathways involved in schizophrenia. ©2008 Macmillan Publishers Limited. All rights reserved., link_to_OA_fulltext

Repetitive transcranial magnetic stimulation (rTMS) has been found to exert modest to substantial antidepressant effects in the majority of prior clinical studies. As effect sizes and stimulation conditions have varied greatly, controversy persists regarding effective stimulation parameters (e.g. intensity, frequency, localization). In the present controlled study, we investigated whether the antidepressant efficacy of rTMS may be related to the stimulation intensity applied. Thirty-one patients suffering from a pharmacotherapy-resistant major depressive episode were randomly assigned to three treatment groups receiving rTMS at different stimulation intensities: (1) intensity at the individual motor threshold (MT); (2) 90% subthreshold intensity; and (3) low intensity of standard sham rTMS. Each patient underwent 10 sessions of 10 Hz rTMS with 1500 stimuli/day over the left dorsolateral prefrontal cortex. Improvement of depressive symptoms after rTMS significantly increased with stimulation intensity across the three groups. A 30% to 33% reduction of baseline depression scores was observed after rTMS at MT intensity. Similarly, groups differed significantly regarding the clinical course after rTMS with the lowest number of antidepressant interventions and the shortest hospital stay in the MT intensity group. These findings support the hypothesis of a relationship between stimulation intensity of rTMS and its antidepressant efficacy.

The most prominent biochemical finding in schizophrenic patients with negative symptoms appears to be the reduction in central dopaminergic, serotoner-gic and noradrenergic activity. This decrease in amine activity tends to be associated with structural brain abnormalities, i.e., cortical atrophy or enlarged ventricles. There are indications that typical neuroleptics reduce those negative symptoms of schizophrenia that are secondary to positive symptoms when these are effectively treated. However, negative symptoms of schizophrenia that occur independently of positive symptoms may also be reduced with monoamine oxidase inhibitors and atypical antipsychotic drugs, such as clozapine. The latter’s efficacy seems to be related to their pharmacological profile, i.e., their interference with dopaminergic, noradrenergic and seroto-nergic receptor systems and metabolism.