Early onset of treatment effects with oral risperidone

BACKGROUND: The dogma of a delayed onset of antipsychotic treatment effects has been maintained over the past decades. However, recent studies have challenged this concept. We therefore performed an analysis of the onset of antipsychotic treatment effects in a sample of acutely decompensated patients with schizophrenia. METHODS: In this observational study, 48 inpatients with acutely decompensated schizophrenia were offered antipsychotic treatment with oral risperidone. PANSS-ratings were obtained on day 0, day 1, day 3, day 7 and day 14. RESULTS: Significant effects of treatment were already present on day 1 and continued throughout the study. The PANSS positive subscore and the PANSS total score improved significantly more than the PANSS negative subscore. CONCLUSION: Our results are consistent with the growing number of studies suggesting an early onset of antipsychotic treatment effects. However, non-pharmacological effects of treatment also need to be taken into consideration

Schizotypy and Behavioural Adjustment and the Role of Neuroticism

In the present study the relationship between behavioural adjustment following cognitive conflict and schizotypy was investigated using a Stroop colour naming paradigm. Previous research has found deficits with behavioural adjustment in schizophrenia patients. Based on these findings, we hypothesized that individual differences in schizotypy, a personality trait reflecting the subclinical expression of the schizophrenia phenotype, would be associated with behavioural adjustment. Additionally, we investigated whether such a relationship would be explained by individual differences in neuroticism, a non-specific measure of negative trait emotionality known to be correlated with schizotypy. 106 healthy volunteers (mean age: 25.1, 60% females) took part. Post-conflict adjustment was measured in a computer-based version of the Stroop paradigm. Schizotypy was assessed using the Schizotypal Personality Questionnaire (SPQ) and Neuroticism using the NEO-FFI. We found a negative correlation between schizotypy and post-conflict adjustment (r = -.30, p<.01); this relationship remained significant when controlling for effects of neuroticism. Regression analysis revealed that particularly the subscale No Close Friends drove the effect. Previous findings of deficits in cognitive control in schizophrenia patients were extended to the subclinical personality expression of the schizophrenia phenotype and found to be specific to schizotypal traits over and above the effects of negative emotionality

Degree correlations in directed scale-free networks

Scale-free networks, in which the distribution of the degrees obeys a power-law, are ubiquitous in the study of complex systems. One basic network property that relates to the structure of the links found is the degree assortativity, which is a measure of the correlation between the degrees of the nodes at the end of the links. Degree correlations are known to affect both the structure of a network and the dynamics of the processes supported thereon, including the resilience to damage, the spread of information and epidemics, and the efficiency of defence mechanisms. Nonetheless, while many studies focus on undirected scale-free networks, the interactions in real-world systems often have a directionality. Here, we investigate the dependence of the degree correlations on the power-law exponents in directed scale-free networks. To perform our study, we consider the problem of building directed networks with a prescribed degree distribution, providing a method for proper generation of power-law-distributed directed degree sequences. Applying this new method, we perform extensive numerical simulations, generating ensembles of directed scale-free networks with exponents between~2 and~3, and measuring ensemble averages of the Pearson correlation coefficients. Our results show that scale-free networks are on average uncorrelated across directed links for three of the four possible degree-degree correlations, namely in-degree to in-degree, in-degree to out-degree, and out-degree to out-degree. However, they exhibit anticorrelation between the number of outgoing connections and the number of incoming ones. The findings are consistent with an entropic origin for the observed disassortativity in biological and technological networks.Comment: 10 pages, 5 figure

Quetiapine in the treatment of schizophrenia and related disorders

Quetiapine was developed in 1985 by scientists at AstraZeneca (formerly Zeneca) Pharmaceuticals. It received official US Food and Drug Administration approval in September 1997 and approval in Germany in 2000. Since then, quetiapine has been used in the treatment of severe mental illness in approximately 70 countries including Canada, most Western European countries, and Japan. Quetiapine is a dibenzothiazepine derivative with a relatively broad receptor binding profile. It has major affinity to cerebral serotonergic (5HT2A), histaminergic (H1), and dopaminergic D1 and D2 receptors, moderate affinity to α1- und α2-adrenergic receptors, and minor affinity to muscarinergic M1 receptors; it demonstrates a substantial selectivity for the limbic system. This receptor occupancy profile with relatively higher affinity for the 5HT2A receptor compared with the D2 receptor is in part responsible for the antipsychotic characteristics and low incidence of extrapyramidal side-effects of quetiapine. The efficacy of quetiapine in reducing positive and negative symptoms of schizophrenia has been proven in several clinical trials with placebo-controlled comparators. Quetiapine has also demonstrated robust efficacy for treatment of cognitive, anxious-depressive, and aggressive symptoms in schizophrenia. Long-term trials show sustained tolerability for a broad spectrum of symptoms. Quetiapine has also proven efficacy and tolerability in the treatment of moderate to severe manic episodes, and in the treatment of juveniles with oppositional-defiant or conduct disorders, and in the geriatric dementia population. Recent data indicate that quetiapine may also be effective in the treatment of bipolar depressive symptoms without increasing the risk of triggering manic episodes, and in borderline personality disorder. In comparison with other antipsychotics, quetiapine has a favorable side-effect profile. In clinical trials only small insignificant prolongations of the QT interval were observed. Weight-gain liabilities and new-onset metabolic side-effects occupy a middle-ground among newer antipsychotics. As a result of its good efficacy and tolerability profile quetiapine has become well established in the treatment of schizophrenia and manic episodes

Analysis of eight genes modulating interferon gamma and human genetic susceptibility to tuberculosis: a case-control association study

<p>Abstract</p> <p>Background</p> <p>Interferon gamma is a major macrophage-activating cytokine during infection with <it>Mycobacterium tuberculosis</it>, the causative pathogen of tuberculosis, and its role has been well established in animal models and in humans. This cytokine is produced by activated T helper 1 cells, which can best deal with intracellular pathogens such as <it>M. tuberculosis</it>. Based on the hypothesis that genes which regulate interferon gamma may influence tuberculosis susceptibility, we investigated polymorphisms in eight candidate genes.</p> <p>Methods</p> <p>Fifty-four polymorphisms in eight candidate genes were genotyped in over 800 tuberculosis cases and healthy controls in a population-based case-control association study in a South African population. Genotyping methods used included the SNPlex Genotyping System™, capillary electrophoresis of fluorescently labelled PCR products, TaqMan^®SNP genotyping assays or the amplification mutation refraction system. Single polymorphisms as well as haplotypes of the variants were tested for association with TB using statistical analyses.</p> <p>Results</p> <p>A haplotype in interleukin 12B was nominally associated with tuberculosis (p = 0.02), but after permutation testing, done to assess the significance for the entire analysis, this was not globally significant. In addition a novel allele was found for the interleukin 12B D5S2941 microsatellite.</p> <p>Conclusions</p> <p>This study highlights the importance of using larger sample sizes when attempting validation of previously reported genetic associations. Initial studies may be false positives or may propose a stronger genetic effect than subsequently found to be the case.</p

Nobody Is Perfect: ERP Effects Prior to Performance Errors in Musicians Indicate Fast Monitoring Processes

Background: One central question in the context of motor control and action monitoring is at what point in time errors can be detected. Previous electrophysiological studies investigating this issue focused on brain potentials elicited after erroneous responses, mainly in simple speeded response tasks. In the present study, we investigated brain potentials before the commission of errors in a natural and complex situation. Methodology/Principal Findings: Expert pianists bimanually played scales and patterns while the electroencephalogram (EEG) was recorded. Event-related potentials (ERPs) were computed for correct and incorrect performances. Results revealed differences already 100 ms prior to the onset of a note (i.e., prior to auditory feedback). We further observed that erroneous keystrokes were delayed in time and pressed more slowly. Conclusions: Our data reveal neural mechanisms in musicians that are able to detect errors prior to the execution of erroneous movements. The underlying mechanism probably relies on predictive control processes that compare the predicted outcome of an action with the action goal

Publication Bias in Antipsychotic Trials: An Analysis of Efficacy Comparing the Published Literature to the US Food and Drug Administration Database

A comparison of data held by the U.S. Food and Drug Administration (FDA) against data from journal reports of clinical trials enables estimation of the extent of publication bias for antipsychotics

Future response of global coastal wetlands to sea-level rise.

The response of coastal wetlands to sea-level rise during the twenty-first century remains uncertain. Global-scale projections suggest that between 20 and 90 per cent (for low and high sea-level rise scenarios, respectively) of the present-day coastal wetland area will be lost, which will in turn result in the loss of biodiversity and highly valued ecosystem services1-3. These projections do not necessarily take into account all essential geomorphological4-7 and socio-economic system feedbacks8. Here we present an integrated global modelling approach that considers both the ability of coastal wetlands to build up vertically by sediment accretion, and the accommodation space, namely, the vertical and lateral space available for fine sediments to accumulate and be colonized by wetland vegetation. We use this approach to assess global-scale changes in coastal wetland area in response to global sea-level rise and anthropogenic coastal occupation during the twenty-first century. On the basis of our simulations, we find that, globally, rather than losses, wetland gains of up to 60 per cent of the current area are possible, if more than 37 per cent (our upper estimate for current accommodation space) of coastal wetlands have sufficient accommodation space, and sediment supply remains at present levels. In contrast to previous studies1-3, we project that until 2100, the loss of global coastal wetland area will range between 0 and 30 per cent, assuming no further accommodation space in addition to current levels. Our simulations suggest that the resilience of global wetlands is primarily driven by the availability of accommodation space, which is strongly influenced by the building of anthropogenic infrastructure in the coastal zone and such infrastructure is expected to change over the twenty-first century. Rather than being an inevitable consequence of global sea-level rise, our findings indicate that large-scale loss of coastal wetlands might be avoidable, if sufficient additional accommodation space can be created through careful nature-based adaptation solutions to coastal management.Personal research fellowship of Mark Schuerch (Project Number 272052902) and by the Cambridge Coastal Research Unit (Visiting Scholar Programme). Furthermore, this work has partly been supported by the EU research project RISES-AM- (FP7-ENV-693396)