Phosphodiesterase 8A to discriminate in blood samples depressed patients and suicide attempters from healthy controls based on A-to-I RNA editing modifications
Abstract Mental health issues, including major depressive disorder, which can lead to suicidal behavior, are considered by the World Health Organization as a major threat to global health. Alterations in neurotransmitter signaling, e.g., serotonin and glutamate, or inflammatory response have been li...
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Series: | Translational Psychiatry |
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doaj-bca99aa3dff34829b47596cc87a00f802021-05-02T11:47:56ZengNature Publishing GroupTranslational Psychiatry2158-31882021-04-0111111110.1038/s41398-021-01377-9Phosphodiesterase 8A to discriminate in blood samples depressed patients and suicide attempters from healthy controls based on A-to-I RNA editing modificationsNicolas Salvetat0Fabrice Chimienti1Christopher Cayzac2Benjamin Dubuc3Francisco Checa-Robles4Pierrick Dupre5Sandie Mereuze6Vipul Patel7Catherine Genty8Jean-Philippe Lang9Jean-François Pujol10Philippe Courtet11Dinah Weissmann12ALCEDIAG/Sys2Diag, CNRS UMR 9005, Parc Euromédecine, Cap DeltaALCEDIAG/Sys2Diag, CNRS UMR 9005, Parc Euromédecine, Cap DeltaALCEDIAG/Sys2Diag, CNRS UMR 9005, Parc Euromédecine, Cap DeltaALCEDIAG/Sys2Diag, CNRS UMR 9005, Parc Euromédecine, Cap DeltaALCEDIAG/Sys2Diag, CNRS UMR 9005, Parc Euromédecine, Cap DeltaALCEDIAG/Sys2Diag, CNRS UMR 9005, Parc Euromédecine, Cap DeltaALCEDIAG/Sys2Diag, CNRS UMR 9005, Parc Euromédecine, Cap DeltaALCEDIAG/Sys2Diag, CNRS UMR 9005, Parc Euromédecine, Cap DeltaDepartment of Emergency Psychiatry and Acute Care, University Hospital/INSERM U1061ALCEDIAG/Sys2Diag, CNRS UMR 9005, Parc Euromédecine, Cap DeltaALCEDIAG/Sys2Diag, CNRS UMR 9005, Parc Euromédecine, Cap DeltaDepartment of Emergency Psychiatry and Acute Care, University Hospital/INSERM U1061ALCEDIAG/Sys2Diag, CNRS UMR 9005, Parc Euromédecine, Cap DeltaAbstract Mental health issues, including major depressive disorder, which can lead to suicidal behavior, are considered by the World Health Organization as a major threat to global health. Alterations in neurotransmitter signaling, e.g., serotonin and glutamate, or inflammatory response have been linked to both MDD and suicide. Phosphodiesterase 8A (PDE8A) gene expression is significantly decreased in the temporal cortex of major depressive disorder (MDD) patients. PDE8A specifically hydrolyzes adenosine 3′,5′-cyclic monophosphate (cAMP), which is a key second messenger involved in inflammation, cognition, and chronic antidepressant treatment. Moreover, alterations of RNA editing in PDE8A mRNA has been described in the brain of depressed suicide decedents. Here, we investigated PDE8A A-to-I RNA editing-related modifications in whole blood of depressed patients and suicide attempters compared to age-matched and sex-matched healthy controls. We report significant alterations of RNA editing of PDE8A in the blood of depressed patients and suicide attempters with major depression, for which the suicide attempt took place during the last month before sample collection. The reported RNA editing modifications in whole blood were similar to the changes observed in the brain of suicide decedents. Furthermore, analysis and combinations of different edited isoforms allowed us to discriminate between suicide attempters and control groups. Altogether, our results identify PDE8A as an immune response-related marker whose RNA editing modifications translate from brain to blood, suggesting that monitoring RNA editing in PDE8A in blood samples could help to evaluate depressive state and suicide risk.https://doi.org/10.1038/s41398-021-01377-9 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Nicolas Salvetat Fabrice Chimienti Christopher Cayzac Benjamin Dubuc Francisco Checa-Robles Pierrick Dupre Sandie Mereuze Vipul Patel Catherine Genty Jean-Philippe Lang Jean-François Pujol Philippe Courtet Dinah Weissmann |
spellingShingle |
Nicolas Salvetat Fabrice Chimienti Christopher Cayzac Benjamin Dubuc Francisco Checa-Robles Pierrick Dupre Sandie Mereuze Vipul Patel Catherine Genty Jean-Philippe Lang Jean-François Pujol Philippe Courtet Dinah Weissmann Phosphodiesterase 8A to discriminate in blood samples depressed patients and suicide attempters from healthy controls based on A-to-I RNA editing modifications Translational Psychiatry |
author_facet |
Nicolas Salvetat Fabrice Chimienti Christopher Cayzac Benjamin Dubuc Francisco Checa-Robles Pierrick Dupre Sandie Mereuze Vipul Patel Catherine Genty Jean-Philippe Lang Jean-François Pujol Philippe Courtet Dinah Weissmann |
author_sort |
Nicolas Salvetat |
title |
Phosphodiesterase 8A to discriminate in blood samples depressed patients and suicide attempters from healthy controls based on A-to-I RNA editing modifications |
title_short |
Phosphodiesterase 8A to discriminate in blood samples depressed patients and suicide attempters from healthy controls based on A-to-I RNA editing modifications |
title_full |
Phosphodiesterase 8A to discriminate in blood samples depressed patients and suicide attempters from healthy controls based on A-to-I RNA editing modifications |
title_fullStr |
Phosphodiesterase 8A to discriminate in blood samples depressed patients and suicide attempters from healthy controls based on A-to-I RNA editing modifications |
title_full_unstemmed |
Phosphodiesterase 8A to discriminate in blood samples depressed patients and suicide attempters from healthy controls based on A-to-I RNA editing modifications |
title_sort |
phosphodiesterase 8a to discriminate in blood samples depressed patients and suicide attempters from healthy controls based on a-to-i rna editing modifications |
publisher |
Nature Publishing Group |
series |
Translational Psychiatry |
issn |
2158-3188 |
publishDate |
2021-04-01 |
description |
Abstract Mental health issues, including major depressive disorder, which can lead to suicidal behavior, are considered by the World Health Organization as a major threat to global health. Alterations in neurotransmitter signaling, e.g., serotonin and glutamate, or inflammatory response have been linked to both MDD and suicide. Phosphodiesterase 8A (PDE8A) gene expression is significantly decreased in the temporal cortex of major depressive disorder (MDD) patients. PDE8A specifically hydrolyzes adenosine 3′,5′-cyclic monophosphate (cAMP), which is a key second messenger involved in inflammation, cognition, and chronic antidepressant treatment. Moreover, alterations of RNA editing in PDE8A mRNA has been described in the brain of depressed suicide decedents. Here, we investigated PDE8A A-to-I RNA editing-related modifications in whole blood of depressed patients and suicide attempters compared to age-matched and sex-matched healthy controls. We report significant alterations of RNA editing of PDE8A in the blood of depressed patients and suicide attempters with major depression, for which the suicide attempt took place during the last month before sample collection. The reported RNA editing modifications in whole blood were similar to the changes observed in the brain of suicide decedents. Furthermore, analysis and combinations of different edited isoforms allowed us to discriminate between suicide attempters and control groups. Altogether, our results identify PDE8A as an immune response-related marker whose RNA editing modifications translate from brain to blood, suggesting that monitoring RNA editing in PDE8A in blood samples could help to evaluate depressive state and suicide risk. |
url |
https://doi.org/10.1038/s41398-021-01377-9 |
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