Exploring gene-drug interactions for personalized treatment of post-traumatic stress disorder
IntroductionPost-Traumatic Stress Disorder (PTSD) is a mental disorder that can develop after experiencing traumatic events. The aim of this work is to explore the role of genes and genetic variations in the development and progression of PTSD.MethodsThrough three methodological approaches, 122 gene...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2024-01-01
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| Series: | Frontiers in Computational Neuroscience |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fncom.2023.1307523/full |
| _version_ | 1797357633526562816 |
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| author | Konstantina Skolariki Panagiotis Vlamos |
| author_facet | Konstantina Skolariki Panagiotis Vlamos |
| author_sort | Konstantina Skolariki |
| collection | DOAJ |
| description | IntroductionPost-Traumatic Stress Disorder (PTSD) is a mental disorder that can develop after experiencing traumatic events. The aim of this work is to explore the role of genes and genetic variations in the development and progression of PTSD.MethodsThrough three methodological approaches, 122 genes and 184 Single Nucleotide Polymorphisms (SNPs) associated with PTSD were compiled into a single gene repository for PTSD. Using PharmGKB and DrugTargetor, 323 drug candidates were identified to target these 122 genes. The top 17 drug candidates were selected based on the statistical significance of the genetic associations, and their promiscuity (number of associated genestargets) and were further assessed for their suitability in terms of bioavailability and drug-like characteristics. Through functional analysis, insights were gained into the biological processes, cellular components, and molecular functions involved in PTSD. This formed the foundation for the next aspect of this study which was to propose an efficient treatment for PTSD by exploring drug repurposing methods.ResultsThe main aim was to identify the drugs with the most favorable profile that can be used as a pharmacological approach for PTSD treatment. More in particular, according to the genetic variations present in each individual, the relevant biological pathway can be identified, and the drug candidate proposed will specifically target said pathway, accounting for the personalized aspect of this work. The results showed that the drugs used as off-label treatment for PTSD have favorable pharmacokinetic profiles and the potential drug candidates that arose from DrugTargetor were not very promising. Clozapine showed a promising pharmacokinetic profile and has been linked with decreased psychiatric symptoms. Ambrucin also showed a promising pharmacokinetic profile but has been mostly linked with cancer treatment. |
| first_indexed | 2024-03-08T14:48:03Z |
| format | Article |
| id | doaj.art-7b0e9903777142a49e519adb02a10592 |
| institution | Directory Open Access Journal |
| issn | 1662-5188 |
| language | English |
| last_indexed | 2024-03-08T14:48:03Z |
| publishDate | 2024-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Computational Neuroscience |
| spelling | doaj.art-7b0e9903777142a49e519adb02a105922024-01-11T05:26:40ZengFrontiers Media S.A.Frontiers in Computational Neuroscience1662-51882024-01-011710.3389/fncom.2023.13075231307523Exploring gene-drug interactions for personalized treatment of post-traumatic stress disorderKonstantina SkolarikiPanagiotis VlamosIntroductionPost-Traumatic Stress Disorder (PTSD) is a mental disorder that can develop after experiencing traumatic events. The aim of this work is to explore the role of genes and genetic variations in the development and progression of PTSD.MethodsThrough three methodological approaches, 122 genes and 184 Single Nucleotide Polymorphisms (SNPs) associated with PTSD were compiled into a single gene repository for PTSD. Using PharmGKB and DrugTargetor, 323 drug candidates were identified to target these 122 genes. The top 17 drug candidates were selected based on the statistical significance of the genetic associations, and their promiscuity (number of associated genestargets) and were further assessed for their suitability in terms of bioavailability and drug-like characteristics. Through functional analysis, insights were gained into the biological processes, cellular components, and molecular functions involved in PTSD. This formed the foundation for the next aspect of this study which was to propose an efficient treatment for PTSD by exploring drug repurposing methods.ResultsThe main aim was to identify the drugs with the most favorable profile that can be used as a pharmacological approach for PTSD treatment. More in particular, according to the genetic variations present in each individual, the relevant biological pathway can be identified, and the drug candidate proposed will specifically target said pathway, accounting for the personalized aspect of this work. The results showed that the drugs used as off-label treatment for PTSD have favorable pharmacokinetic profiles and the potential drug candidates that arose from DrugTargetor were not very promising. Clozapine showed a promising pharmacokinetic profile and has been linked with decreased psychiatric symptoms. Ambrucin also showed a promising pharmacokinetic profile but has been mostly linked with cancer treatment.https://www.frontiersin.org/articles/10.3389/fncom.2023.1307523/fullpost-traumatic stress disordergenetic biomarkersmathematical modelingsystem pharmacologyfunctional analysis |
| spellingShingle | Konstantina Skolariki Panagiotis Vlamos Exploring gene-drug interactions for personalized treatment of post-traumatic stress disorder Frontiers in Computational Neuroscience post-traumatic stress disorder genetic biomarkers mathematical modeling system pharmacology functional analysis |
| title | Exploring gene-drug interactions for personalized treatment of post-traumatic stress disorder |
| title_full | Exploring gene-drug interactions for personalized treatment of post-traumatic stress disorder |
| title_fullStr | Exploring gene-drug interactions for personalized treatment of post-traumatic stress disorder |
| title_full_unstemmed | Exploring gene-drug interactions for personalized treatment of post-traumatic stress disorder |
| title_short | Exploring gene-drug interactions for personalized treatment of post-traumatic stress disorder |
| title_sort | exploring gene drug interactions for personalized treatment of post traumatic stress disorder |
| topic | post-traumatic stress disorder genetic biomarkers mathematical modeling system pharmacology functional analysis |
| url | https://www.frontiersin.org/articles/10.3389/fncom.2023.1307523/full |
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