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

Mahdi Malekpour; Aida Jafari; Mohammad Kashkooli; Seyed Reza Salarikia; Manica Negahdaripour

doi:10.3389/fpsyt.2023.1116892

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

Front Psychiatry. 2023 May 12:14:1116892. doi: 10.3389/fpsyt.2023.1116892. eCollection 2023.

Authors

Mahdi Malekpour¹, Aida Jafari¹, Mohammad Kashkooli¹, Seyed Reza Salarikia¹, Manica Negahdaripour^{2

3}

Affiliations

¹ Student Research Committee, Shiraz University of Medical Sciences, Shiraz, Iran.
² Pharmaceutical Sciences Research Center, Shiraz University of Medical Science, Shiraz, Iran.
³ Department of Pharmaceutical Biotechnology, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran.

Abstract

Objectives: Psychogenic 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.

Methods: Different 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.

Results: Eight 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.

Significance: This 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.

Keywords: PNES; epilepsy; functional seizure; molecular pathogenesis; psychogenic non-epileptic seizure; systems biology.