A systems biology approach for discovering the cellular and molecular aspects of psychogenic non-epileptic seizure

ObjectivesPsychogenic non-epileptic seizure (PNES) is the most common non-epileptic disorder in patients referring to epilepsy centers. Contrary to common beliefs about the disease’s harmlessness, the death rate of PNES patients is similar to drug-resistant epilepsy. Meanwhile, the molecular pathome...

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Main Authors: Mahdi Malekpour, Aida Jafari, Mohammad Kashkooli, Seyed Reza Salarikia, Manica Negahdaripour
Format: Article
Language:English
Published: Frontiers Media S.A. 2023-05-01
Series:Frontiers in Psychiatry
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fpsyt.2023.1116892/full
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author Mahdi Malekpour
Aida Jafari
Mohammad Kashkooli
Seyed Reza Salarikia
Manica Negahdaripour
Manica Negahdaripour
author_facet Mahdi Malekpour
Aida Jafari
Mohammad Kashkooli
Seyed Reza Salarikia
Manica Negahdaripour
Manica Negahdaripour
author_sort Mahdi Malekpour
collection DOAJ
description ObjectivesPsychogenic non-epileptic seizure (PNES) is the most common non-epileptic disorder in patients referring to epilepsy centers. Contrary to common beliefs about the disease’s harmlessness, the death rate of PNES patients is similar to drug-resistant epilepsy. Meanwhile, the molecular pathomechanism of PNES is unknown with very limited related research. Thus, the aim of this in silico study was to find different proteins and hormones associated with PNES via a systems biology approach.MethodsDifferent bioinformatics databases and literature review were used to find proteins associated with PNES. The protein-hormone interaction network of PNES was constructed to discover its most influential compartments. The pathways associated with PNES pathomechanism were found by enrichment analysis of the identified proteins. Besides, the relationship between PNES-related molecules and psychiatric diseases was discovered, and the brain regions that could express altered levels of blood proteins were discovered.ResultsEight genes and three hormones were found associated with PNES through the review process. Proopiomelanocortin (POMC), neuropeptide Y (NPY), cortisol, norepinephrine, and brain-derived neurotrophic factor (BDNF) were identified to have a high impact on the disease pathogenesis network. Moreover, activation of Janus kinase-signaling transducer and activator of transcription (JAK–STAT) and JAK, as well as signaling of growth hormone receptor, phosphatidylinositol 3-kinase /protein kinase B (PI3K/AKT), and neurotrophin were found associated with PNES molecular mechanism. Several psychiatric diseases such as depression, schizophrenia, and alcohol-related disorders were shown to be associated with PNES predominantly through signaling molecules.SignificanceThis study was the first to gather the biochemicals associated with PNES. Multiple components and pathways and several psychiatric diseases associated with PNES, and some brain regions that could be altered during PNES were suggested, which should be confirmed in further studies. Altogether, these findings could be used in future molecular research on PNES patients.
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spelling doaj.art-36dffdd604a344b6b8311e1d1a9fc7db2023-05-12T06:05:45ZengFrontiers Media S.A.Frontiers in Psychiatry1664-06402023-05-011410.3389/fpsyt.2023.11168921116892A systems biology approach for discovering the cellular and molecular aspects of psychogenic non-epileptic seizureMahdi Malekpour0Aida Jafari1Mohammad Kashkooli2Seyed Reza Salarikia3Manica Negahdaripour4Manica Negahdaripour5Student Research Committee, Shiraz University of Medical Sciences, Shiraz, IranStudent Research Committee, Shiraz University of Medical Sciences, Shiraz, IranStudent Research Committee, Shiraz University of Medical Sciences, Shiraz, IranStudent Research Committee, Shiraz University of Medical Sciences, Shiraz, IranPharmaceutical Sciences Research Center, Shiraz University of Medical Science, Shiraz, IranDepartment of Pharmaceutical Biotechnology, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, IranObjectivesPsychogenic non-epileptic seizure (PNES) is the most common non-epileptic disorder in patients referring to epilepsy centers. Contrary to common beliefs about the disease’s harmlessness, the death rate of PNES patients is similar to drug-resistant epilepsy. Meanwhile, the molecular pathomechanism of PNES is unknown with very limited related research. Thus, the aim of this in silico study was to find different proteins and hormones associated with PNES via a systems biology approach.MethodsDifferent bioinformatics databases and literature review were used to find proteins associated with PNES. The protein-hormone interaction network of PNES was constructed to discover its most influential compartments. The pathways associated with PNES pathomechanism were found by enrichment analysis of the identified proteins. Besides, the relationship between PNES-related molecules and psychiatric diseases was discovered, and the brain regions that could express altered levels of blood proteins were discovered.ResultsEight genes and three hormones were found associated with PNES through the review process. Proopiomelanocortin (POMC), neuropeptide Y (NPY), cortisol, norepinephrine, and brain-derived neurotrophic factor (BDNF) were identified to have a high impact on the disease pathogenesis network. Moreover, activation of Janus kinase-signaling transducer and activator of transcription (JAK–STAT) and JAK, as well as signaling of growth hormone receptor, phosphatidylinositol 3-kinase /protein kinase B (PI3K/AKT), and neurotrophin were found associated with PNES molecular mechanism. Several psychiatric diseases such as depression, schizophrenia, and alcohol-related disorders were shown to be associated with PNES predominantly through signaling molecules.SignificanceThis study was the first to gather the biochemicals associated with PNES. Multiple components and pathways and several psychiatric diseases associated with PNES, and some brain regions that could be altered during PNES were suggested, which should be confirmed in further studies. Altogether, these findings could be used in future molecular research on PNES patients.https://www.frontiersin.org/articles/10.3389/fpsyt.2023.1116892/fullPNESpsychogenic non-epileptic seizuresystems biologymolecular pathogenesisepilepsyfunctional seizure
spellingShingle Mahdi Malekpour
Aida Jafari
Mohammad Kashkooli
Seyed Reza Salarikia
Manica Negahdaripour
Manica Negahdaripour
A systems biology approach for discovering the cellular and molecular aspects of psychogenic non-epileptic seizure
Frontiers in Psychiatry
PNES
psychogenic non-epileptic seizure
systems biology
molecular pathogenesis
epilepsy
functional seizure
title A systems biology approach for discovering the cellular and molecular aspects of psychogenic non-epileptic seizure
title_full A systems biology approach for discovering the cellular and molecular aspects of psychogenic non-epileptic seizure
title_fullStr A systems biology approach for discovering the cellular and molecular aspects of psychogenic non-epileptic seizure
title_full_unstemmed A systems biology approach for discovering the cellular and molecular aspects of psychogenic non-epileptic seizure
title_short A systems biology approach for discovering the cellular and molecular aspects of psychogenic non-epileptic seizure
title_sort systems biology approach for discovering the cellular and molecular aspects of psychogenic non epileptic seizure
topic PNES
psychogenic non-epileptic seizure
systems biology
molecular pathogenesis
epilepsy
functional seizure
url https://www.frontiersin.org/articles/10.3389/fpsyt.2023.1116892/full
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