Cargando…
Computational Analysis of Therapeutic Neuroadaptation to Chronic Antidepressant in a Model of the Monoaminergic Neurotransmitter and Stress Hormone Systems
The clinical practice of selective serotonin reuptake inhibitor (SSRI) augmentation relies heavily on trial-and-error. Unfortunately, the drug combinations prescribed today fail to provide relief for many depressed patients. In order to identify potentially more effective treatments, we developed a...
Autores principales: | , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2019
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6823241/ https://www.ncbi.nlm.nih.gov/pubmed/31708770 http://dx.doi.org/10.3389/fphar.2019.01215 |
_version_ | 1783464488928804864 |
---|---|
author | Camacho, Mariam B. Vijitbenjaronk, Warut D. Anastasio, Thomas J. |
author_facet | Camacho, Mariam B. Vijitbenjaronk, Warut D. Anastasio, Thomas J. |
author_sort | Camacho, Mariam B. |
collection | PubMed |
description | The clinical practice of selective serotonin reuptake inhibitor (SSRI) augmentation relies heavily on trial-and-error. Unfortunately, the drug combinations prescribed today fail to provide relief for many depressed patients. In order to identify potentially more effective treatments, we developed a computational model of the monoaminergic neurotransmitter and stress-steroid systems that neuroadapts to chronic administration of combinations of antidepressant drugs and hormones by adjusting the strengths of its transmitter-system components (TSCs). We used the model to screen 60 chronically administered drug/hormone pairs and triples, and identified as potentially therapeutic those combinations that raised the monoamines (serotonin, norepinephrine, and dopamine) but lowered cortisol following neuroadaptation in the model. We also evaluated the contributions of individual and pairs of TSCs to therapeutic neuroadaptation with chronic SSRI using sensitivity, correlation, and linear temporal-logic analyses. All three approaches revealed that therapeutic neuroadaptation to chronic SSRI is an overdetermined process that depends on multiple TSCs, providing a potential explanation for the clinical finding that no single antidepressant regimen alleviates depressive symptoms in all patients. |
format | Online Article Text |
id | pubmed-6823241 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-68232412019-11-08 Computational Analysis of Therapeutic Neuroadaptation to Chronic Antidepressant in a Model of the Monoaminergic Neurotransmitter and Stress Hormone Systems Camacho, Mariam B. Vijitbenjaronk, Warut D. Anastasio, Thomas J. Front Pharmacol Pharmacology The clinical practice of selective serotonin reuptake inhibitor (SSRI) augmentation relies heavily on trial-and-error. Unfortunately, the drug combinations prescribed today fail to provide relief for many depressed patients. In order to identify potentially more effective treatments, we developed a computational model of the monoaminergic neurotransmitter and stress-steroid systems that neuroadapts to chronic administration of combinations of antidepressant drugs and hormones by adjusting the strengths of its transmitter-system components (TSCs). We used the model to screen 60 chronically administered drug/hormone pairs and triples, and identified as potentially therapeutic those combinations that raised the monoamines (serotonin, norepinephrine, and dopamine) but lowered cortisol following neuroadaptation in the model. We also evaluated the contributions of individual and pairs of TSCs to therapeutic neuroadaptation with chronic SSRI using sensitivity, correlation, and linear temporal-logic analyses. All three approaches revealed that therapeutic neuroadaptation to chronic SSRI is an overdetermined process that depends on multiple TSCs, providing a potential explanation for the clinical finding that no single antidepressant regimen alleviates depressive symptoms in all patients. Frontiers Media S.A. 2019-10-25 /pmc/articles/PMC6823241/ /pubmed/31708770 http://dx.doi.org/10.3389/fphar.2019.01215 Text en Copyright © 2019 Camacho, Vijitbenjaronk and Anastasio http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Pharmacology Camacho, Mariam B. Vijitbenjaronk, Warut D. Anastasio, Thomas J. Computational Analysis of Therapeutic Neuroadaptation to Chronic Antidepressant in a Model of the Monoaminergic Neurotransmitter and Stress Hormone Systems |
title | Computational Analysis of Therapeutic Neuroadaptation to Chronic Antidepressant in a Model of the Monoaminergic Neurotransmitter and Stress Hormone Systems |
title_full | Computational Analysis of Therapeutic Neuroadaptation to Chronic Antidepressant in a Model of the Monoaminergic Neurotransmitter and Stress Hormone Systems |
title_fullStr | Computational Analysis of Therapeutic Neuroadaptation to Chronic Antidepressant in a Model of the Monoaminergic Neurotransmitter and Stress Hormone Systems |
title_full_unstemmed | Computational Analysis of Therapeutic Neuroadaptation to Chronic Antidepressant in a Model of the Monoaminergic Neurotransmitter and Stress Hormone Systems |
title_short | Computational Analysis of Therapeutic Neuroadaptation to Chronic Antidepressant in a Model of the Monoaminergic Neurotransmitter and Stress Hormone Systems |
title_sort | computational analysis of therapeutic neuroadaptation to chronic antidepressant in a model of the monoaminergic neurotransmitter and stress hormone systems |
topic | Pharmacology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6823241/ https://www.ncbi.nlm.nih.gov/pubmed/31708770 http://dx.doi.org/10.3389/fphar.2019.01215 |
work_keys_str_mv | AT camachomariamb computationalanalysisoftherapeuticneuroadaptationtochronicantidepressantinamodelofthemonoaminergicneurotransmitterandstresshormonesystems AT vijitbenjaronkwarutd computationalanalysisoftherapeuticneuroadaptationtochronicantidepressantinamodelofthemonoaminergicneurotransmitterandstresshormonesystems AT anastasiothomasj computationalanalysisoftherapeuticneuroadaptationtochronicantidepressantinamodelofthemonoaminergicneurotransmitterandstresshormonesystems |