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The vascular plant pathogenic fungus Verticillium dahliae has to adapt to environmental changes outside and inside its host. V.dahliae harbors homologs of Neurospora crassa clock genes. The molecular functions and interactions of Frequency (Frq) and Frq-interacting RNA helicase (Frh) in controlling conidia or microsclerotia development were investigated in V.dahliae JR2. Fungal mutant strains carrying clock gene deletions, an FRH point mutation, or GFP gene fusions were analyzed on transcript, protein, and phenotypic levels as well as in pathogenicity assays on tomato plants. Our results support that the Frq–Frh complex is formed and that it promotes conidiation, but also that it suppresses and therefore delays V.dahliae microsclerotia formation in response to light. We investigated a possible link between the negative element Frq and positive regulator Suppressor of flocculation 1 (Sfl1) in microsclerotia formation to elucidate the regulatory molecular mechanism. Both Frq and Sfl1 are mainly present during the onset of microsclerotia formation with decreasing protein levels during further development. Induction of microsclerotia formation requires Sfl1 and can be delayed at early time points in the light through the Frq–Frh complex. Gaining further molecular knowledge on V.dahliae development will improve control of fungal growth and Verticillium wilt disease.

Background and Hypothesis Cognitive impairment is a hallmark of schizophrenia, but no effective treatment is available to date. The underlying pathophysiology includes disconnectivity between hippocampal and prefrontal brain regions. Supporting evidence comes from diffusion-weighted imaging studies that suggest abnormal organization of frontotemporal white matter pathways in schizophrenia. Study Design Here, we hypothesize that in schizophrenia, deficient maturation of oligodendrocyte precursor cells (OPCs) into mature oligodendrocytes substantially contributes to abnormal frontotemporal macro- and micro-connectivity and subsequent cognitive deficits. Study Results Our postmortem studies indicate a reduced oligodendrocyte number in the cornu ammonis 4 (CA4) subregion of the hippocampus, and others have reported the same histopathological finding in the dorsolateral prefrontal cortex. Our series of studies on aerobic exercise training showed a volume increase in the hippocampus, specifically in the CA4 region, and improved cognition in individuals with schizophrenia. The cognitive effects were subsequently confirmed by meta-analyses. Cell-specific schizophrenia polygenic risk scores showed that exercise-induced CA4 volume increase significantly correlates with OPCs. From animal models, it is evident that early life stress and oligodendrocyte-related gene variants lead to schizophrenia-related behavior, cognitive deficits, impaired oligodendrocyte maturation, and reduced myelin thickness. Conclusions Based on these findings, we propose that pro-myelinating drugs (e.g., the histamine blocker clemastine) combined with aerobic exercise training may foster the regeneration of myelin plasticity as a basis for restoring frontotemporal connectivity and cognition in schizophrenia.

Vitamin deficiency syndromes and blood–brain barrier (BBB) dysfunction are frequent phenomena in psychiatric conditions. We analysed the largest available first-episode schizophrenia-spectrum psychosis (FEP) cohort to date regarding routine cerebrospinal fluid (CSF) and blood parameters to investigate the association between vitamin deficiencies (vitamin B12 and folate) and BBB impairments in FEP. We report a retrospective analysis of clinical data from all inpatients that were admitted to our tertiary care hospital with an ICD-10 diagnosis of a first-episode F2x (schizophrenia-spectrum) between January 1, 2008 and August 1, 2018 and underwent a lumbar puncture, blood-based vitamin status diagnostics and neuroimaging within the clinical routine. 222 FEP patients were included in our analyses. We report an increased CSF/serum albumin quotient (Qalb) as a sign of BBB dysfunction in 17.1% (38/222) of patients. White matter lesions (WML) were present in 29.3% of patients (62/212). 17.6% of patients (39/222) showed either decreased vitamin B12 levels or decreased folate levels. No statistically significant association was found between vitamin deficiencies and altered Qalb. This retrospective analysis contributes to the discussion on the impact of vitamin deficiency syndromes in FEP. Although decreased vitamin B12 or folate levels were found in approximately 17% of our cohort, we found no evidence for significant associations between BBB dysfunction and vitamin deficiencies. To strengthen the evidence regarding the clinical implications of vitamin deficiencies in FEP, prospective studies with standardized measurements of vitamin levels together with follow-up measurements and assessment of symptom severity in addition to CSF diagnostics are needed.

Background Schizophrenia is accompanied by widespread alterations in static functional connectivity associated with symptom severity and cognitive deficits. Improvements in aerobic fitness have been demonstrated to ameliorate symptomatology and cognition in people with schizophrenia, but the intermediary role of macroscale connectivity patterns remains unknown. Objective Therefore, we aim to explore the relation between aerobic fitness and the functional connectome in individuals with schizophrenia. Further, we investigate clinical and cognitive relevance of the identified fitness-connectivity links. Methods Patients diagnosed with schizophrenia were included in this cross-sectional resting-state fMRI analysis. Multilevel Bayesian partial correlations between aerobic fitness and functional connections across the whole brain as well as between static functional connectivity patterns and clinical and cognitive outcome were performed. Preliminary causal inferences were enabled based on mediation analyses. Results Static functional connectivity between the subcortical nuclei and the cerebellum as well as between temporal seeds mediated the attenuating relation between aerobic fitness and total symptom severity. Functional connections between cerebellar seeds affected the positive link between aerobic fitness and global cognition, while the functional interplay between central and limbic seeds drove the beneficial association between aerobic fitness and emotion recognition. Conclusion The current study provides first insights into the interactions between aerobic fitness, the functional connectome and clinical and cognitive outcome in people with schizophrenia, but causal interpretations are preliminary. Further interventional aerobic exercise studies are needed to replicate the current findings and to enable conclusive causal inferences. Trial registration The study which the manuscript is based on is registered in the International Clinical Trials Database (ClinicalTrials.gov identifier [NCT number]: NCT03466112) and in the German Clinical Trials Register (DRKS-ID: DRKS00009804).

Aerobic exercise is a promising add-on treatment to counteract structural and functional impairments of the hippocampal formation and associated clinical outcome in schizophrenia. However, current evidence regarding exercise effects on the hippocampal formation in schizophrenia is still limited and inconclusive. Therefore, we aim to assess the impact of aerobic exercise on the volume and functional connectivity of the hippocampal formation and explore the clinical relevance of potential exercise-induced adaptations in people with schizophrenia. In this multicenter randomized-controlled clinical trial, a total of 92 patients with schizophrenia underwent serial 3T-MRIs and were randomly assigned to either an aerobic exercise intervention or a flexibility, strengthening and balance training as a control group. Both groups exercised for six months and completed approximately one training session per week on average. Clinical assessments and structural and functional MRI scans were conducted at three consecutive timepoints. Linear mixed models, linear and logistic regressions and mediation analyses were computed to examine the effects of exercise on the volume and connectivity of the hippocampal formation and their potential clinical relevance. In the aerobic exercise group, but not in the control group, volumes within the hippocampal formation increased, especially in CA3. No effects of exercise on functional connectivity of the hippocampal formation were observed. The present study indicates that aerobic exercise in people with schizophrenia can lead to volumetric increases within the hippocampal formation with most robust effects on CA3. Hence, the current findings support previous evidence that aerobic exercise can prevent neurodegenerative processes in this key region.

Negative symptoms and cognitive deficits are common in individuals with schizophrenia, greatly affect their outcome, and have been associated with alterations in cerebral gray and white matter volume (GMV, WMV). In the last decade, aerobic endurance training has emerged as a promising intervention to alleviate these symptoms and improved aerobic fitness has been suggested as a key moderator variable. In the present study, we investigated, whether aerobic fitness is associated with fewer cognitive deficits and negative symptoms and with GMVs and WMVs in individuals with schizophrenia in a cross-sectional design. In the largest study to date on the implications of fitness in individuals with schizophrenia, 111 participants at two centers underwent assessments of negative symptoms, cognitive functioning, and aerobic fitness and 69 underwent additional structural magnetic resonance imaging. Multilevel Bayesian partial correlations were computed to quantify relationships between the variables of interest. The main finding was a positive association of aerobic fitness with right hippocampal GMV and WMVs in parahippocampal and several cerebellar regions. We found limited evidence for an association of aerobic fitness with cognitive functioning and negative symptoms. In summary, our results strengthen the notion that aerobic fitness and hippocampal plasticity are interrelated which holds implications for the design of exercise interventions in individuals with schizophrenia.

Background: Vitamin deficiency syndromes and blood-brain-barrier (BBB) dysfunction are frequent phenomena in psychiatric conditions. We analysed the largest available first-episode psychosis (FEP) cohort to date regarding routine cerebrospinal fluid (CSF) and blood parameters to investigate the association between vitamin deficiencies (vitamin B12 and folate) and BBB impairments in FEP. Methods: We report a retrospective analysis of clinical data from all inpatients that were admitted to our tertiary care hospital with an ICD-10 diagnosis of a first-episode F2x (schizophrenia-spectrum) between January 1, 2008 and August 1, 2018 and underwent a lumbar puncture and blood-based vitamin status diagnostics within the clinical routine. Results: 222 FEP patients were included in our analyses. We report an increased CSF/serum albumin quotient (Qalb) as a sign of BBB dysfunction in 17.1% (38/222) of patients. White matter lesions (WML) were present in 29.3% of patients (62/212). 17.6% of patients (39/222) showed either decreased vitamin B12 levels or decreased folate levels. No statistically significant association was found between impairments in vitamin levels and an altered Qalb.Conclusions: This retrospective analysis contributes to the discussion on the impact of vitamin deficiency syndromes in FEP. Although decreased vitamin B12 or folate levels were found in approximately 17% of our cohort, we found no evidence for significant associations between BBB dysfunction and vitamin deficiencies. To strengthen the evidence regarding the clinical implications of vitamin deficiencies in FEP, prospective studies with standardized measurements of vitamin levels together with follow-up measurements and assessment of symptom severity in addition to CSF diagnostics are needed.

Even today, patients with schizophrenia often have an unfavorable outcome. Negative symptoms and cognitive deficits are common features in many patients and prevent recovery. In recent years, aerobic endurance training has emerged as a therapeutic approach with positive effects on several domains of patients’ health. However, appropriately sized, multicenter randomized controlled trials that would allow better generalization of results are lacking. The exercise study presented here is a multicenter, rater-blind, two-armed, parallel-group randomized clinical trial in patients with clinically stable schizophrenia being conducted at five German tertiary hospitals. The intervention group performs aerobic endurance training on bicycle ergometers three times per week for 40–50 min/session (depending on the intervention week) for a total of 26 weeks, and the control group performs balance and tone training for the same amount of time. Participants are subsequently followed up for 26 weeks. The primary endpoint is all-cause discontinuation; secondary endpoints include psychopathology, cognition, daily functioning, cardiovascular risk factors, and explorative biological measures regarding the underlying mechanisms of exercise. A total of 180 patients will be randomized. With currently 162 randomized participants, our study is the largest trial to date to investigate endurance training in patients with schizophrenia. We hypothesize that aerobic endurance training has beneficial effects on patients’ mental and physical health, leading to lower treatment discontinuation rates and improving disease outcomes. The study results will provide a basis for recommending exercise interventions as an add-on therapy in patients with schizophrenia.The study is registered in the International Clinical Trials Database (ClinicalTrials.gov identifier [NCT number]: NCT03466112) and in the German Clinical Trials Register (DRKS-ID: DRKS00009804).

grant Klinische Forschergruppe (KFO) from the Deutsche Forschungsgemeinschaft (DFG)German Research Foundation (DFG) [241]

Major depression, bipolar disorder, and schizophrenia are severe mental illnesses. Despite receiving psychopharmacological and psychosocial treatments, about half of patients develop a chronic course with residual cognitive and negative symptoms and have a high risk for cardiovascular disease and reduced life expectancy. Therefore, add-on innovative treatment approaches are needed to improve outcome. Aerobic exercise interventions have been shown to improve global functioning, cognition, and negative and depressive symptoms in these patients. The basic mechanism of these exercise-related changes has been reported to be improved brain plasticity, e.g., increased volume of disease-related brain regions such as the hippocampus. The optimal type, duration, and frequency of exercise have not yet been determined and need to be addressed in supervised physical exercise studies. Because of the low physical activity levels, lack of drive related to negative and depressive symptoms, and high prevalence of cardiovascular comorbidities in patients with severe mental illness, besides aiming to improve symptoms of mental illness, exercise interventions should also aim to increase cardiorespiratory fitness, which they should comprehensively assess by direct measurements of maximal oxygen uptake. Based on the recommendations for developing cardiorespiratory fitness by the American College of Sports Medicine, 150 min moderate-intensity training per week or vigorous-intensity exercise training for 75 min per week are appropriate. Most studies have had relatively short intervention periods, so future studies should focus on long-term adherence to exercise by implementing motivational strategies supported by telemedicine and by identifying and targeting typical barriers to exercise in this patient population.

Verticillia cause a vascular wilt disease affecting a broad range of economically valuable crops. The fungus enters its host plants through the roots and colonizes the vascular system. It requires extracellular proteins for a successful plant colonization. The exoproteome of the allodiploidVerticillium longisporumwas analyzed upon cultivation in different media. Secreted fungal proteins were identified by label free LC-MS/MS screening.V. longisporuminduced two main secretion patterns. One response pattern was elicited in various non-plant related environments. The second pattern includes the exoprotein responses to the plant-related media, pectin-rich simulated xylem medium and pure xylem sap, which exhibited similar but additional distinct features. These exoproteomes include a shared core set of 223 secreted and similarly enriched fungal proteins. The pectin-rich medium significantly induced the secretion of 144 proteins including a number of pectin degrading enzymes, whereas xylem sap triggered a smaller but unique fungal exoproteome pattern with 32 enriched proteins. The latter pattern included proteins with domains of known effectors, metallopeptidases and carbohydrate-active enzymes. The most abundant and uniquely enriched proteins of these different groups are the necrosis and ethylene inducing-like proteins Nlp2 and Nlp3, the cerato-platanin proteins Cp1 and Cp2, the metallopeptidases Mep1 and Mep2 and the CAZys Gla1, Amy1 and Cbd1. Deletion of the majority of the corresponding genes caused no phenotypic changes duringex plantagrowth or invasion and colonization of tomato plants. However, we discovered that theNLP2andNLP3deletion strains were compromised in plant infections. Overall, our exoproteome approach revealed that the fungus induces specific secretion responses in different environments. The fungus has a general response to non-plant related media whereas it is able to fine-tune its exoproteome in the presence of plant material. Importantly, the xylem sap-specific exoproteome pinpointed Nlp2 and Nlp3 as single effectors required for successfulV. dahliaecolonization.Author SummaryVerticilliumspp. infect hundreds of different plants world-wide leading to enormous economic losses. Verticillium wilt is a disease of the vasculature. The fungus colonizes the xylem of its host plant where it exploits the vascular system to colonize the whole plant. Therefore, the fungus spends part of its lifetime in this nutrient-low and imbalanced environment where it is inaccessible for disease control treatments. This lifestyle as well requires the fungus to react to plant defense responses by secreting specific effector molecules to establish a successful infection. We addressed the differences in media-dependent secretion responses ofVerticillium longisporum. We identified a broad response pattern induced by several media, and a similar response (but with some distinct differences) for the plant-related environments: the pectin-rich medium SXM and xylem sap from the host rapeseed. Importantly, we show that the necrosis and ethylene inducing-like proteins Nlp2 and Nlp3 are xylem sap-specific proteins that are required for fullV. dahliaepathogenicity on tomato. These factors play a role during the colonization phase and represent potential targets for new control strategies for Verticillium wilt.

SummaryDevelopment and virulence of the vascular plant pathogen Verticillium dahliae are connected and depend on a complex interplay between the unfolded protein response, a Ham5 independent pheromone MAP kinase module and formation of precursors for oxylipin signal molecules.Genes coding for the unfolded protein response regulator Hac1, the Ham5 MAPK scaffold protein, and the oleate Δ12-fatty acid desaturase Ode1 were deleted and their functions in growth, differentiation, and virulence on plants were studied using genetic, cell biology, and plant infection experiments.The unfolded protein response transcription factor Hac1 is required for initial root colonization, fungal conidiation and propagation inside the host and is essential for resting structure formation. Microsclerotia development, growth and virulence require the pheromone response MAPK pathway, but without the Ham5 scaffold function. Single ER-associated enzymes for linoleic acid production make important contributions to fungal growth but have only a minor impact on the pathogenicity of V. dahliae.Fungal growth, sporulation, dormant structure formation and plant infection require a network of the Hac1-regulated unfolded protein response, a scaffold-independent pheromone response MAPK pathway and formation of precursors for signalling. This network includes interesting targets for disease management of the vascular pathogen V. dahliae.

Background Even though clozapine is the recommended last-resort antipsychotic, many patients fail to respond and show treatment-refractory psychotic symptoms. Smoking has been suggested as a possible risk factor for poor clozapine response, hampering remission and negatively impacting somatic outcomes. Methods Our aim was to test whether smoking status is associated with remission rates and other symptomatic and somatic outcomes. We therefore assessed remission rates according to The Remission in Schizophrenia Working Group (RSWG) criteria, and metabolic and cognitive outcomes among patients with schizophrenia-spectrum disorders treated with clozapine for at least 6 months. For analyses, we grouped our cohort into 3 groups according to clozapine treatment duration (6 months, 2 years, 5 years). Results One hundred five patients were included in our analyses and grouped according to their clozapine treatment duration. In the 6-months analyses, patients who smoked were significantly more likely to be younger of age (p=0.002) despite on average shorter duration of clozapine treatment (p=0.041) and significantly more likely to be treated with mood-stabilizing co-medication (p=0.030) compared to nonsmokers. Remission rates (p=0.490), as well as a set of metabolic and cognitive variables did not differ between the 2 groups. A related pattern could be observed for the 2- and 5-years analyses. Conclusions Smoking behavior among clozapine-treated schizophrenia patients might delineate a cohort with an earlier onset of the disease. Nevertheless, most findings comparing disease-specific and clinical outcomes among smokers and nonsmokers were negative. Further research is needed to identify strategies to overcome insufficient remission rates in this patient group.

Item does not contain fulltext Aerobic exercise is a promising intervention for patients with schizophrenia, but structural neuroplastic effects on brain regions relevant to the pathophysiology of the disease remain unclear. This study aimed to elucidate longitudinal changes in cortical thickness after aerobic exercise intervention in schizophrenia patients and the relationship of these changes to clinical correlates. We investigated 21 schizophrenia patients and 23 healthy controls who performed aerobic exercise and 21 schizophrenia patients who played table soccer. The 12-week exercise intervention was combined with computer-assisted cognitive remediation training from week 6 to week 12. Magnetic resonance imaging (MRI) scans were acquired at baseline and weeks 6,12, and 24. The thickness of the entorhinal, parahippocampal, and lateral and medial prefrontal cortices was assessed with FreeSurfer 6.0. The schizophrenia aerobic exercise group showed a significant increase of cortical thickness in the right entorhinal cortex at week 6, and we found a significant correlation between the cortical thickness of the right lateral prefrontal cortex at baseline and improvement of social adaptation at week 12. In the schizophrenia table soccer and healthy control groups, we found no significant longitudinal change in cortical thickness through the intervention and follow-up period and no correlation of cortical thickness at baseline with clinical measures. Our results suggest that aerobic exercise in schizophrenia modulates the thickness of the entorhinal cortex, a structure adjacent to the hippocampus. Greater cortical thickness of the right lateral prefrontal cortex appears to predict better clinical response to an aerobic exercise intervention in patients with schizophrenia. 11 p.

Background Cortical plasticity – the ability to reorganize synaptic connections and adapt to environmental changes – appears to be impaired in schizophrenia patients. Results suggest the dysfunctional plasticity to be a key pathophysiological mechanism. Different non-invasive brain stimulation (NIBS) techniques have been used to modulate and induce cortical plasticity. In healthy subjects, nicotine was shown to play an important role in plasticity induction and is capable to alter cortical excitability and plasticity, induced by NIBS techniques. Our goal was to investigate the promising effects of a nicotine receptor activation done by Varenicline and the combination with anodal transcranial direct current stimulation (a-tDCS) on neuroplastic changes in schizophrenia patients. Methods Our sample consisted out of twenty-four individuals with schizophrenia, twelve smokers and twelve non-smokers. Every participant received Varenicline and Placebo, combined with anodal transcranial direct current stimulation (a-tDCS), to induce non-focal plasticity. We inferred plasticity changes by monitoring changes in cortical excitability. This was done via motor-evoked potentials (MEPs) elicited by transcranial magnetic stimulation (TMS). The MEPs were recorded before and three hours after Varenicline/Placebo intake. Following the direct current stimulation, we monitored excitability changes for up to one hour. Results Significant effects through the mere Varenicline consumption or withdrawal effects could not be found in any group. However, we observed a numeric temporary decrease of excitability after a-tDCS in non-smokers following Varenicline intake. This decrease compared to the placebo condition was visible 20 minutes after a-tDCS but vanished over time. Smokers did not show any excitability changes after a-tDCS and the nicotinic receptor stimulation did not show any influence. Excitability changes after stimulation in contrast to the baseline measurement were not evident. Discussion Our results show that an activation of nicotinic receptors in schizophrenia patients does not induce excitability changes. The modulating effect of nicotine in plasticity induction via anodal transcranial direct current stimulation could not be confirmed for patients with schizophrenia. We could show that chronic nicotine consumption in patients with schizophrenia or nicotine withdrawal does not lead to fundamental excitability changes. Acute nicotine consumption has only small effects on cortical excitability in non-smokers.

Higher glutamate and glutamine (together: Glx) and lower N-acetyl-aspartate (NAA) levels were reported in schizophrenia. Endurance training normalizes NAA in the hippocampus, but its effects on other metabolites in the brain and the relationship of metabolites to clinical symptoms remain unknown. For 12 weeks, 20 schizophrenia inpatients (14 men, 6 women) and 23 healthy controls (16 men, 7 women) performed endurance training and a control group of 21 schizophrenia inpatients (15 men, 6 women) played table soccer. A computer-assisted cognitive performance training program was introduced after 6 weeks. We assessed cognitive performance, psychopathological symptoms, and everyday functioning at baseline and after 6 and 12 weeks and performed single voxel magnetic resonance spectroscopy of the hippocampus, left dorsolateral prefrontal cortex (DLPFC), and thalamus. We quantified NAA, Glx, total creatine (tCr), calculated NAA/tCr and Glx/tCr and correlated these ratios with physical fitness, clinical and neurocognitive scores, and everyday functioning. At baseline, in both schizophrenia groups NAA/tCr was lower in the left DLPFC and left hippocampus and Glx/tCr was lower in the hippocampus than in the healthy controls. After 6 weeks, NAA/tCr increased in the left DLPFC in both schizophrenia groups. Brain metabolites did not change significantly in the hippocampus or thalamus, but the correlation between NAA/tCr and Glx/tCr normalized in the left DLPFC. Global Assessment of Functioning improvements correlated with NAA/tCr changes in the left DLPFC. In our study, endurance training and table soccer induced normalization of brain metabolite ratios in the brain circuitry associated with neuronal and synaptic elements, including metabolites of the glutamatergic system.

Cognitive symptoms are a core feature of schizophrenia and are related to an unfavorable disease outcome. So far, there are no satisfactory pharmacological approaches to address cognitive symptoms. For some time now, aerobic exercise has been demonstrated in various trials to be a promising candidate for this indication. The aim of this brief qualitative review was to present the most recent meta-analyses regarding the capacity of exercise to improve cognition in schizophrenia patients. Additionally, we give a short overview of the effects in other conditions, like healthy subjects and patients with major depression. We conducted a focused literature search using the PubMed database, concentrating on meta-analyses which are based on a systematic search. The most recent meta-analysis investigating the efficacy of aerobic exercise on cognitive impairments in schizophrenia patients provides evidence that exercise has positive effects on cognitive functioning in this population. However, the effect seems not to be specific; there were positive findings regarding healthy subjects and patients with depressive disorders as well, even if they were less consistent. As most available trials have a small to modest sample size and have no consensus with regard to the intervention regime, nor to the assessment of cognition, the findings are difficult to generalize. In the future, standardized clinical trials focusing on the long-term effects of exercise are needed to evaluate whether the improvements in cognition are sustainable. .Los síntomas cognitivos constituyen una característica central de la esquizofrenia y se relacionan con un resultado desfavorable de la enfermedad. Hasta la fecha, no hay enfoques farmacológicos efectivos para abordar los síntomas cognitivos. Desde hace algún tiempo, se ha demostrado en varios ensayos que el ejercicio aeróbico es un candidato prometedor para esta indicación. El objetivo de esta breve revisión cualitativa fue presentar los resultados de meta-análisis más recientes sobre la capacidad del ejercicio para mejorar la cognición en pacientes con esquizofrenia. Además, se ofrece una breve descripción de los efectos del ejercicio en sujetos sanos y en pacientes con depresión mayor. Se realizó una búsqueda bibliográfica dirigida en la base de datos PubMed, focalizada en estudios de meta-análisis basados en una revisión sistemática. El meta-análisis más reciente que investiga la eficacia del ejercicio aeróbico en el deterioro cognitivo en pacientes con esquizofrenia proporciona evidencia de que el ejercicio tiene efectos positivos sobre el funcionamiento cognitivo en esta población. Sin embargo, el efecto no parece ser específico; también hubo resultados positivos -aunque menos constantes- en sujetos sanos y en pacientes con trastornos depresivos. Los hallazgos son difíciles de generalizar ya que la mayoría de los ensayos disponibles tienen un tamaño muestral pequeño o moderado y no hay consenso con respecto al tipo de intervención, ni a la evaluación de la cognición. En el futuro, se requiere de ensayos clínicos estandarizados que se centren en los efectos a largo plazo del ejercicio para evaluar si las mejorías en la cognición son duraderas.Les symptômes cognitifs sont une caractéristique essentielle de la schizophrénie et sont liés à une évolution péjorative de la maladie. Il n’existe pas à ce jour de traitement pharmacologique satisfaisant pour les symptômes cognitifs. Différentes études ont montré depuis un certain temps maintenant, que l’exercice aérobie était prometteur dans cette indication. Cette brève mise au point qualitative a pour but de présenter les méta-analyses les plus récentes sur la capacité d’amélioration de la cognition des patients schizophrènes par l’exercice physique. Nous faisons en outre une revue rapide des effets dans d’autres circonstances comme les sujets sains et les patients souffrant de dépression majeure. Nous nous sommes concentrés sur des méta-analyses basées sur une recherche systématique dans la base de données PubMed pour réaliser une recherche ciblée de la littérature. Les méta-analyses les plus récentes à propos de l’efficacité de l’exercice aérobie sur les déficits cognitifs dans la schizophrénie montrent que l’exercice a des effets positifs sur le fonctionnement cognitif dans cette population. Cependant, ces effets ne semblent pas spécifiques ; les résultats sont également positifs pour les sujets sains et les patients atteints de troubles dépressifs même si ils sont moins constants. Il est difficile de généraliser les résultats car la taille des échantillons de la plupart des études disponibles est petite voire négligeable et il n’y a pas de consensus en ce qui concerne les traitements ni l’évaluation de la cognition. À l’avenir, des études cliniques standardisées sur les effets à long terme de l’exercice sont nécessaires pour évaluer la durabilité des améliorations de la cognition.

Schizophrenia is a severe neuropsychiatric disease that is associated with neurobiological alterations in multiple brain regions and peripheral organs. Negative symptoms and cognitive deficits are present in about half of patients and are difficult to treat, leading to an unfavorable functional outcome. To investigate the impact of aerobic exercise on various neurobiological parameters, we conducted a narrative review. Add-on aerobic exercise was shown to be effective in improving negative and general symptoms, cognition, global functioning, and quality of life in schizophrenia patients. Based on findings in healthy individuals and animal models, this qualitative review gives an overview of different lines of evidence on how aerobic exercise impacts brain structure and function and molecular mechanisms in patients with schizophrenia and how its effects could be related to clinical and functional outcomes. Structural magnetic resonance imaging studies showed a volume increase in the hippocampus and cortical regions in schizophrenia patients and healthy controls after endurance training. However, results are inconsistent and individual risk factors may influence neuroplastic processes. Animal studies indicate that alterations in epigenetic mechanisms and synaptic plasticity are possible underlying mechanisms, but that differentiation of glial cells, angiogenesis, and possibly neurogenesis may also be involved. Clinical and animal studies also revealed effects of aerobic exercise on the hypothalamus-pituitary-adrenal axis, growth factors, and immune-related mechanisms. Some findings indicate effects on neurotransmitters and the endocannabinoid system. Further research is required to clarify how individual risk factors in schizophrenia patients mediate or moderate the neurobiological effects of exercise on brain and cognition. Altogether, aerobic exercise is a promising candidate in the search for pathophysiology-based add-on interventions in schizophrenia.

Contains fulltext : 220348.pdf (Publisher’s version ) (Open Access) This is a data article from the original publication "Effect of aerobic exercise combined with cognitive remediation on cortical thickness and prediction of social adaptation in patients with schizophrenia"[1]. Twenty-one patients with schizophrenia and 23 healthy controls underwent aerobic exercise. Another 21 patients with schizophrenia played table soccer instead. The 12-week exercise intervention was combined with computer-assisted cognitive remediation training from week 6 to week 12. Clinical assessments were conducted at baseline and after the 12-week intervention. Magnetic resonance imaging (MRI) scans were acquired at baseline then in weeks 6, 12, and 24. The thickness of the entorhinal, parahippocampal, and lateral and medial prefrontal cortices was assessed with FreeSurfer 6.0. Data are publicy available via https://osf.io/sfgxk/. 6 p.

Background: Preclinical studies recently showed that the mineralocorticoid antagonist spironolactone acts also as an antagonist of the NRG1-ERBB4 signaling pathway and improves schizophrenia-like behaviour in Nrg1 transgenic mouse model. As this signaling pathway is critically linked to the pathophysiology of schizophrenia, especially in the context of working-memory dysfunction, spironolactone may be a novel treatment option for patients with schizophrenia targeting cognitive impairments. Aims: To evaluate whether spironolactone added to an ongoing antipsychotic treatment improves cognitive functioning in schizophrenia. Methods: The add-on spironolactone for the treatment of schizophrenia trial (SPIRO-TREAT) is a multicenter randomized, placebo-controlled trial with three arms (spironolactone 100 mg, spironolactone 200 mg and placebo). Schizophrenia patients are treated for three weeks and then followed-up for additional nine weeks. As primary outcome, we investigate changes in working memory before and at the end of the intervention phase. We will randomize 90 patients. Eighty-one patients are intended to reach the primary endpoint measure at the end of the three-week intervention period. Secondary endpoints include other measures of cognition, psychopathology, safety measures and biological measures. Conclusions: SPIRO-TREAT is the first study evaluating the efficacy of the mineralocorticoid receptor antagonist spironolactone to improve cognitive impairments in schizophrenia patients targeting the NRG1-ERBB4 signaling pathway. With SPIRO-TREAT, we intend to investigate a novel treatment option for cognitive impairments in schizophrenia that goes beyond the established concepts of interfering with dopaminergic neurotransmission as key pathway in schizophrenia treatment. Clinical trial registration: International Clinical Trials Registry Platform: http://apps.who.int/trialsearch/Trial2.aspx?TrialID=EUCTR2014-001968-35-DE Keywords: Schizophrenia, Cognitive impairment, Spironolactone, NRG1-ERBB4, Drug repositioning, Drug repurposing

Oomycetes, also named Peronosporomycetes, are one of the most important and widespread groups of plant pathogens, leading to significant losses in the global agricultural productivity. They have been studied extensively in ground water, soil, and host plants, but their atmospheric transport vector is not well characterized. In this study, the occurrence of airborne Oomycetes was investigated by Sanger sequencing and quantitative PCR of coarse and fine aerosol particle samples (57 filter pairs) collected over a 1-year period (2006–2007) and full seasonal cycle in Mainz, Germany. In coarse particulate matter, we found 55 different hypothetical species (OTUs), of which 54 were plant pathogens and 29 belonged to the genus Peronospora (downy mildews). In fine particulate matter (

ZusammenfassungDie Schizophrenie geht häufig mit einer verminderten sozialen Funktion aufgrund kognitiver Defizite einher, die mit gehirnstrukturellen Veränderungen wie einer Verminderung des Hippocampusvolumens assoziiert sind. In einer ersten Studie haben wir eine Verbesserung des episodischen Gedächtnisses und eine Volumenvergrößerung des Hippocampus nach aerobem Sporttraining bei Menschen mit einer Mehrfacherkrankung einer Schizophrenie gefunden. In einer Folgestudie unter Kombination mit kognitivem Training konnten wir eine Vergrößerung des temporalen Kortex zeigen, allerdings fanden wir für die Gesamtgruppe keine signifikante Zunahme des Hippocampusvolumens. Bei diesen Patienten war jedoch ein erhöhter polygenetischer Risikofaktor (Polygenetic Risk Score, PRS) mit einer verminderten Volumenzunahme des Hippocampus assoziiert sowie verbesserter körperlicher Fitness und psychosozialen Funktionsniveau. In der Sportstudie (Clinical-Trials.gov ID: NCT03466112) des „Enhancing Schizophrenia Prevention and Recovery through Innovative Treatments” (ESPRIT) Forschungsnetzwerkes zu psychischen Erkrankungen erweitern wir die Dauer des Trainings nach den Richtlinien des American College of Sports Medicine. Langzeiteffekte des Ausdauertrainings auf Kognition, Symptome und funktionelle Genesung werden verglichen mit einer Kontrollgruppe, die Gleichgewichtsübungen und Muskeltonustraining durchführt.