Browsing by Subject "Schizophrenia"
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(2020)It is challenging to identify causal genes and pathways explaining the associations with diseases and traits found by genome-wide association studies (GWASs). To solve this problem, a variety of methods that prioritize genes based on the variants identified by GWASs have been developed. In this thesis, the methods Data-driven Expression Prioritized Integration for Complex Traits (DEPICT) and Multi-marker Analysis of GenoMic Annotation (MAGMA) are used to prioritize causal genes based on the most recently published publicly available schizophrenia GWAS summary statistics. The two methods are compared using the Benchmarker framework, which allows an unbiased comparison of gene prioritization methods. The study has four aims. Firstly, to explain what are the differences between the gene prioritization methods DEPICT and MAGMA and how the two methods work. Secondly, to explain how the Benchmarker framework can be used to compare gene prioritization methods in an unbiased way. Thirdly, to compare the performance of DEPICT and MAGMA in prioritizing genes based on the latest schizophrenia summary statistics from 2018 using the Benchmarker framework. Lastly, to compare the performance of DEPICT and MAGMA on a schizophrenia GWAS with a smaller sample size by using Benchmarker. Firstly, the published results of the Benchmarker analyses using schizophrenia GWAS from 2014 were replicated to make sure that the framework is run correctly. The results were very similar and both the original and the replicated results show that DEPICT and MAGMA do not perform significantly differently. Furthermore, they show that the intersection of genes prioritized by DEPICT and MAGMA outperforms the outersection, which is defined as genes prioritized by only one of these methods. Secondly, Benchmarker was used to compare the performance of DEPICT and MAGMA on prioritizing genes using the schizophrenia GWAS from 2018. The results of the Benchmarker analyses suggest that DEPICT and MAGMA perform similarly with the GWAS from 2018 compared to the GWAS from 2014. Furthermore, an earlier schizophrenia GWAS from 2011 was used to check if the performance of DEPICT and MAGMA differs when a GWAS with lower statistical power is used. The results of the Benchmarker analyses make clear that MAGMA performs better than DEPICT in prioritizing genes using this smaller data set. Furthermore, for the schizophrenia GWAS from 2011 the outersection of genes prioritized by DEPICT and MAGMA outperforms the intersection. To conclude, the Benchmarker framework is a useful tool for comparing gene prioritization methods in an unbiased way. For the most recently published schizophrenia GWAS from 2018 there is no significant difference between the performance of DEPICT and MAGMA in prioritizing genes according to Benchmarker. For the smaller schizophrenia GWAS from 2011, however, MAGMA outperformed DEPICT.
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(2016)Background Constipation and dyspepsia are disturbing gastrointestinal symptoms that are often ignored in research on physical comorbidities of schizophrenia. Aims Our aim was to assess dyspepsia and constipation in a sample of outpatients with schizophrenia spectrum psychoses. Methods A general practitioner performed a thorough physical health check for 275 outpatients and diagnosed constipation and dyspepsia. We assessed the possible contribution of several sociodemographic, lifestyle, and clinical variables to constipation and dyspepsia using logistic regression analysis. We also assessed whether these symptoms were associated with abnormal laboratory findings. Results The prevalence of constipation was 31.3%, and of dyspepsia 23.6%. Paracetamol (OR=3.07, 95% CI 1.34–7.02) and clozapine use (OR=5.48, 95% CI 2.75–10.90), older age (OR=1.04, 95% CI 1.01–1.06), and living in sheltered housing (OR=2.49, 95% CI 1.16–5.33) were risk factors for constipation. For dyspepsia the risk factors were female sex (OR=2.10, 95% CI 1.15–3.83), non-steroidal anti-inflammatory drugs (OR=2.47, 95% CI 1.13–5.39), and diabetes medication (OR=2.42, 95% CI 1.12–5.25). Patients with dyspepsia had lower hemoglobin and hematocrit and higher glucose values than those without dyspepsia. Patients with constipation had lower thrombocyte values than patients without constipation. However, these findings were explained by factors predisposing to constipation and dyspepsia. Conclusions Clozapine use markedly increases the risk of constipation and may lead to life-threatening complications. In addition, analgesics and diabetes medication were related to gastrointestinal symptoms. These medications and their association to gastrointestinal symptoms should be kept in mind when treating patients with schizophrenia.
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(2020)Goals. Schizophrenia is a neuropsychiatric disorder characterized with cognitive symptoms such as memory deficits and sleep disturbances. Sleep spindle (slow ~10Hz, fast ~13Hz) activity has been found to correlate with declarative and procedural memory performance. Having enough of spindles might not guarantee intact sleep-dependent memory consolidation, but their temporal coordination with neocortical slow oscillations (SOs) and hippocampal ripples (100-250Hz) needs to be considered. SOs temporally group thalamic spindle and hippocampal ripple activity thus creating coordinated brain activity that has been proposed to be responsible for the redistribution of recently encoded memories from temporary dependence on the hippocampus to longer term representation in the cortex. Synchronized SO-spindle activity has been observed to predict overnight memory consolidation. Abnormalities in sleep spindle parameters and synchronized SO-spindle activity have been proposed to explain memory performance deficits present in schizophrenia. The purpose of this review is to familiarize the reader with the current research on the relationship between sleep spindles and memory performance in schizophrenia, and to provide an understanding of the possible role of coordinated SO-spindle activity in this relationship. Methods. This integrated literature review was constituted of articles that build up an understanding of the basic mechanisms of sleep spindles and memory consolidation. The scope was then extended to cover articles concerning the synchronization of sleep spindles and slow oscillations, and its relation to memory performance in schizophrenia patients. Results and conclusions. Some studies observed reduced sleep spindle parameters such as sleep spindle number and density predicting less overnight improvement in memory performance in schizophrenia patients. Cortex-wide synchronized SO-spindle activity was found to predict overnight improvement in healthy controls but not in schizophrenia patients, whereas synchronized SO-spindle activity measured from local brain areas was observed to predict overnight improvement in patients. The result indicates that distributed SO-spindle synchrony could present a hallmark of impaired memory performance in schizophrenia patients.
Now showing items 1-3 of 3