Disfunção pré-frontoparietal durante o processamento de informação visuoauditiva em pacientes idosos com esquizofrenia crônica e efeitos da medicação

OBJECTIVES: In first-episode schizophrenia patients, functional magnetic resonance imaging (fMRI) has shown prefronto-parietal dysfunction during acoustic and visual stimulation. The aim of this study was to investigate the prefronto-parietal network in elderly schizophrenia patients using the same paradigm. Additionally, we hypothesized favourable effects on brain activation by the atypical antipsychotic clozapine compared to typical neuroleptics. METHODS: We investigated 18 elderly, chronic schizophrenia patients and 21 elderly healthy controls. Nine schizophrenia patients had been medicated with clozapine and 9 had been receiving typical neuroleptics over decades. In addition to assessments with psychopathological and neuropsychological rating scales we used an acoustic and visual stimulation paradigm in a 1.5 Tesla MRI scanner to investigate BOLD-response in different brain areas. RESULTS: Compared to healthy controls schizophrenia patients showed decreased brain activation in the prefrontal and parietal cortex as well as medial anterior cingulate gyrus compared to healthy controls. In these regions, patients medicated with clozapine showed increased BOLD-response compared to patients treated with typical neuroleptics. DISCUSSION: Our study confirmed prefronto-parietal network disturbances in elderly schizophrenia patients thus pointing to the preservation of brain activation deficits and the influence of neurodevelopmental disturbances in chronic schizophrenia until old-age. CONCLUSION: The atypical antipsychotic clozapine seems to facilitate brain activation even in elderly, chronic schizophrenia patients.OBJETIVOS: Em pacientes com primeiro episódio de esquizofrenia, estudos com ressonância magnética funcional (RMf) têm demonstrado disfunção pré-frontoparietal durante estimulação acústica e visual. O objetivo do presente estudo foi investigar a rede pré-frontoparietal em pacientes idosos com esquizofrenia utilizando o mesmo paradigma. Adicionalmente, foram presumidos efeitos favoráveis na ativação cerebral pelo antipsicótico atípico clozapina em comparação a neurolépticos típicos. MÉTODOS: Foram investigados 18 pacientes com esquizofrenia crônica e 21 controles saudáveis idosos. Nove pacientes com esquizofrenia haviam sido medicados com clozapina e nove haviam recebido neurolépticos típicos por décadas. Concomitantemente às avaliações com escalas psicopatológicas e neuropsicológicas foi utilizado um paradigma de estimulação auditiva e visual em um aparelho de ressonância magnética de 1,5 Tesla para investigar a resposta BOLD em diferentes áreas cerebrais. RESULTADOS: Comparados a controles saudáveis, os pacientes com esquizofrenia apresentaram diminuição na ativação cerebral nos córtices pré-frontal e parietal, assim como no giro do cíngulo anterior medial. Nessas regiões, os pacientes medicados com clozapina apresentaram resposta BOLD aumentada em comparação aos pacientes tratados com neurolépticos típicos. DISCUSSÃO: O presente estudo confirmou a presença de distúrbios na rede pré-frontoparietal em pacientes idosos com esquizofrenia, apontando assim para a preservação de déficits de ativação cerebrais e a influência de distúrbios do desenvolvimento neural em esquizofrenia crônica até a velhice. CONCLUSÃO: O antipsicótico atípico clozapina parece facilitar a ativação de áreas cerebrais mesmo em pacientes idosos com esquizofrenia crônica

Assessment of the anionic composition of the soil with the influence of eartworms activity

We established by capillary electrophoresis method that earthworms increase the chloride ion content and reduce the content of sulfate, nitrate and phosphate ions in experimental mesocosm soils. With increasing depth, the concentration of all anions decreases

Rationale and design of the randomised clinical trial comparing early medication change (EMC) strategy with treatment as usual (TAU) in patients with Major Depressive Disorder - the EMC trial

<p>Abstract</p> <p>Background</p> <p>In Major Depressive Disorder (MDD), the traditional belief of a delayed onset of antidepressants' effects has lead to the concept of current guidelines that treatment durations should be between 3-8 weeks before medication change in case of insufficient outcome. Post hoc analyses of clinical trials, however, have shown that improvement usually occurs within the first 10-14 days of treatment and that such early improvement (Hamilton Depression Rating Scale [HAMD] decrease ≥20%) has a substantial predictive value for final treatment outcome. Even more important, non-improvement (HAMD decrease <20%) after 14 days of treatment was found to be highly predictive for a poor final treatment outcome.</p> <p>Methods/Design</p> <p>The EMC trial is a phase IV, multi-centre, multi-step, randomized, observer-blinded, actively controlled parallel-group clinical trial to investigate for the first time prospectively, whether non-improvers after 14 days of antidepressant treatment with an early medication change (EMC) are more likely to attain remission (HAMD-17 ≤7) on treatment day 56 compared to patients treated according to current guideline recommendation (treatment as usual; TAU). In level 1 of the EMC trial, non-improvers after 14 days of antidepressant treatment will be randomised to an EMC strategy or TAU. The EMC strategy for this study schedules a first medication change on day 15; in case of non-improvement between days 15-28, a second medication change will be performed. TAU schedules the first medication change after 28 days in case of non-response (HAMD-17 decrease <50%). Both interventions will last 42 days. In levels 2 and 3, EMC strategies will be compared with TAU strategies in improvers on day 14, who experience a stagnation of improvement during the course of treatment. The trial is supported by the German Federal Ministry of Education and Research (BMBF) and will be conducted in cooperation with the BMBF funded Interdisciplinary Centre Clinical Trials (IZKS) at the University Medical Centre Mainz and at six clinical trial sites in Germany.</p> <p>Discussion</p> <p>If the EMC strategies lead to significantly more remitters, changes of clinical practice, guidelines for the treatment of MDD as well as research settings can be expected.</p> <p>Trial Registration</p> <p><b>Clincaltrials.gov Identifier</b>: NCT00974155; <b>EudraCT</b>: 2008-008280-96.</p

Peripheral blood and neuropsychological markers for the onset of action of antidepressant drugs in patients with Major Depressive Disorder

<p>Abstract</p> <p>Background</p> <p>In Major Depressive Disorder (MDD), treatment outcomes with currently available strategies are often disappointing. Therefore, it is sensible to develop new strategies to increase remission rates in acutely depressed patients. Many studies reported that true drug response can be observed within 14 days (early improvement) of antidepressant treatment. The identical time course of symptom amelioration after early improvement in patients treated with antidepressants of all classes or with placebo strongly suggests a common biological mechanism, which is not specific for a particular antidepressant medication. However, the biology underlying early improvement and final treatment response is not understood and there is no established biological marker as yet, which can predict treatment response for the individual patient before initiation or during the course of antidepressant treatment. Peripheral blood markers and executive functions are particularly promising candidates as markers for the onset of action and thus the prediction of final treatment outcome in MDD.</p> <p>Methods/Design</p> <p>The present paper presents the rationales, objectives and methods of a multi-centre study applying close-meshed repetitive measurements of peripheral blood and neuropsychological parameters in patients with MDD and healthy controls during a study period of eight weeks for the identification of biomarkers for the onset of antidepressants' action in patients with MDD. Peripheral blood parameters and depression severity are assessed in weekly intervals from baseline to week 8, executive performance in bi-weekly intervals. Patients are participating in a randomized controlled multi-level clinical trial, healthy controls are matched according to mean age, sex and general intelligence.</p> <p>Discussion</p> <p>This investigation will help to identify a biomarker or a set of biomarkers with decision-making quality in the treatment of MDD in order to increase the currently disappointing remission rates of antidepressant treatment.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov: <a href="http://www.clinicaltrials.gov/ct2/show/NCT00974155">NCT00974155</a></p

Real-Time direct volume rendering in functional magnetic resonance imaging

Direct volume rendering is a visualization method that allows display of all information hidden in three-dimensional data sets of, for example, computed tomography or magnetic resonance imaging (MRI). In contrast to commonly used surface rendering methods, these algorithms need no preprocessing but suffer from a high computational complexity. A real-time rendering system, VIRIM (Vitec: Visualization Technology GmbH, Mannheim, Germany), cuts down rendering times of minutes on normal workstations to an interactive rate of 1 second or less. The immediate visual feedback allows interactive steering of the visualization process to achieve insight into the internal three-dimensional structure of objects. Additional information is obtained by using an interactive gray-value segmentation tool that both allows segmentation of the data set according to bone, tissue, and liquor and display of multifunctional data sets (e.g., functional MRI [fMRI] data sets). Thus, real-time direct volume rendering allows segmentation and volume data processing of functional and anatomical MR data sets simultaneously. As this method can be integrated in the clinical routine, it is of great importance for real-time motion artifact detection and the interpretation of fMRI data acquired during cognitive experiments with normal subjects and psychiatric patients. Because of the free programmability of VIRIM, more complex matching procedures are currently being investigated for future implementation

Predictors of the effectiveness of an early medication change strategy in patients with major depressive disorder

Abstract Background Patients with Major Depressive Disorder (MDD) who are non-improvers after two weeks of antidepressant treatment have a high risk of treatment failure. Recently, we did not find differences in outcomes in non-improvers randomized to an early medication change (EMC) strategy compared to treatment as usual (TAU). This secondary analysis investigated possible predictors of higher remission rates in the EMC strategy. Methods Of 192 non-improvers (i.e. decrease of ≤20% on the HAMD-17 depression scale) after a two-week treatment with escitalopram, n = 97 were randomized to EMC (immediate switch to high doses of venlafaxine XR) and n = 95 to TAU (continued escitalopram until day 28 with non-responders switched to venlafaxine XR). We first analyzed patient characteristics, psychopathological features and subtypes of MDD by logistic regression analyses as possible predictors of remission rates. In a second investigation, we analyzed the predictors, which showed a significant association in the first analysis before Bonferroni-Holm correction by chi-squared tests separated for treatment groups. All analyses were corrected by Bonferroni-Holm method. Results The first analyses yielded no statistically significant results after correction for multiple testing. In the second analyses, however, patients with prior medication at study entry showed higher remission rates in EMC than in TAU (24.2% versus 8.6%, p = 0.017; Bonferroni-Holm corrected significance level: p = 0.025.). Furthermore, patients with a recurrent course of MDD benefited less from treatment as usual (p = 0.009; Bonferroni-Holm corrected significance level: p = 0.025). Age, sex, age of onset, psychiatric or somatic comorbidities, and other subtypes of MDD did not predict remission rates. Conclusions Although in our first analysis we found statistically non-significant results, the second analysis showed significant differences in remission rates between patients with or without previous medication and in patients with recurrent MDD or the first depressive episode. It would therefore be valuable to examine in larger and prospective studies whether remission rates can be increased by quick escalation of treatment in certain subgroups of patients. Promising subgroups to be tested are patients who were previously medicated, and who show a recurrent course of MDD. Trial registration clinicaltrials.gov Identifier: NCT00974155. Registered at the 10th of September 2009. Retrospectively registered