Dataset Information

Epilepsy as a Network Disorder (2): What can we learn from other network disorders such as dementia and schizophrenia, and what are the implications for translational research?

ABSTRACT: There is common agreement that many disorders of the central nervous system are 'complex', that is, there are many potential factors that influence the development of the disease, underlying mechanisms, and successful treatment. Most of these disorders, unfortunately, have no cure at the present time, and therapeutic strategies often have debilitating side effects. Interestingly, some of the 'complexities' of one disorder are found in another, and the similarities are often network defects. It seems likely that more discussions of these commonalities could advance our understanding and, therefore, have clinical implications or translational impact. With this in mind, the Fourth International Halifax Epilepsy Conference and Retreat was held as described in the prior paper, and this companion paper focuses on the second half of the meeting. Leaders in various subspecialties of epilepsy research were asked to address aging and dementia or psychosis in people with epilepsy (PWE). Commonalities between autism, depression, aging and dementia, psychosis, and epilepsy were the focus of the presentations and discussion. In the last session, additional experts commented on new conceptualization of translational epilepsy research efforts. Here, the presentations are reviewed, and salient points are highlighted.

SUBMITTER: Scharfman HE

PROVIDER: S-EPMC5756681 | biostudies-other | 2018 Jan

REPOSITORIES: biostudies-other

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Epilepsy as a Network Disorder (2): What can we learn from other network disorders such as dementia and schizophrenia, and what are the implications for translational research?

Scharfman Helen E HE Kanner Andres M AM Friedman Alon A Blümcke Ingmar I Crocker Candice E CE Cendes Fernando F Diaz-Arrastia Ramon R Förstl Hans H Fenton André A AA Grace Anthony A AA Palop Jorge J Morrison Jason J Nehlig Astrid A Prasad Asuri A Wilcox Karen S KS Jette Nathalie N Pohlmann-Eden Bernd B

Epilepsy & behavior : E&B 20171031

There is common agreement that many disorders of the central nervous system are 'complex', that is, there are many potential factors that influence the development of the disease, underlying mechanisms, and successful treatment. Most of these disorders, unfortunately, have no cure at the present time, and therapeutic strategies often have debilitating side effects. Interestingly, some of the 'complexities' of one disorder are found in another, and the similarities are often network defects. It s ...[more]

PMID: 29097123

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Project description:Despite of multiple systematic studies of schizophrenia pathogenesis, reconstruction of the mechanism established on proteomics, metabolomics, and genome-wide significant loci is still a challenging task. We suggested that advanced data for quantitative proteomics, metabolomics, and genome-wide association study (GWAS) may enhance the current evidence and fundamental knowledge about molecular pathogenesis of schizophrenia. Liquide chromatography and ultra-high-resolution mass-spectrometry were utilized for proteomic and metabolomic assay, and high throughput genotyping for the GWAS study. Proteomic and metabolomic results were quantitatively evaluated and overlayed on the GWAS data. After statistical analysis using R-package, the resulting features were associated in a multilayer mode with adjusted biological processes in a reconstructed unified map of molecular events. We have identified 20 DFE proteins that were validated on an independent cohort of patients that are significant for schizophrenia, including ALS, A1AG1, PEDF, VTDB, CERU, APOB, APOH, FASN, GPX3, etc. Almost half of them are new for schizophrenia. The metabolomic survey revealed 18 compounds most of which were the part transformation of tyrosine and steroids with the incline to androgens (androsterone sulfate, thyroliberin, thyroxine, dihydrotestosterone, androstenedione, cholesterol sulfate, metanephrine, dopaquinone, etc.) which were extracted as group-specific determinants that permits to isolate patients with schizophrenia. The GWAS assay revealed 52 loci were integrated into proteome-metabolome data as significantly implicated in schizophrenia. We integrated three layers of omics science (proteomics, metabolomics and GWAS) and quantitative analysis utilized systematic approach to reconstruct the proposed map of molecular events associated with the considered psychopathology. The resulting interplay between different layers emphasized strict implication of lipids metabolism, oxidative stress, imbalance in steroidogenesis and associated impartments of thyroid hormones and sex hormones interconnection. The proposed interplay map can give opportunity in the understanding how the regulation of distinct metabolic axis is achieved and what happens in proteome arrangements to produce a schizophrenia-specific pattern of pathology condition.

Dataset Information

Epilepsy as a Network Disorder (2): What can we learn from other network disorders such as dementia and schizophrenia, and what are the implications for translational research?

Publications

Epilepsy as a Network Disorder (2): What can we learn from other network disorders such as dementia and schizophrenia, and what are the implications for translational research?

Similar Datasets

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