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Nitric Oxide Synthase activity in major depressive episodes before and after antidepressant treatment: Results of a large case-control treatment study

Published online by Cambridge University Press:  11 June 2020

E. Loeb ,
K. El Asmar ,
S. Trabado ,
F. Gressier ,
R. Colle ,
A. Rigal ,
S. Martin ,
C. Verstuyft ,
B. Fève  and
P. Chanson
...Show all authors
E. Loeb
Affiliation:
INSERM CESP - Equipe ‘Moods’- Univ Paris-Saclay, 94275 Le Kremlin Bicêtre, France Service de Psychiatrie- Hôpital Bicêtre- GH Paris Saclay- APHP, 94275 Le Kremlin Bicêtre, France Faculté de Médecine Paris-Saclay, 94275 Le Kremlin Bicêtre, France
K. El Asmar
Affiliation:
INSERM CESP - Equipe ‘Moods’- Univ Paris-Saclay, 94275 Le Kremlin Bicêtre, France
S. Trabado
Affiliation:
Faculté de Médecine Paris-Saclay, 94275 Le Kremlin Bicêtre, France Inserm U1185 - Univ Paris-Sud, 94275 Le Kremlin Bicêtre, France Service de Génétique moléculaire, Pharmacogénétique et Hormonologie- CHU de Bicêtre- APHP, 94275 Le Kremlin Bicêtre, France
F. Gressier
Affiliation:
INSERM CESP - Equipe ‘Moods’- Univ Paris-Saclay, 94275 Le Kremlin Bicêtre, France Service de Psychiatrie- Hôpital Bicêtre- GH Paris Saclay- APHP, 94275 Le Kremlin Bicêtre, France Faculté de Médecine Paris-Saclay, 94275 Le Kremlin Bicêtre, France
R. Colle
Affiliation:
INSERM CESP - Equipe ‘Moods’- Univ Paris-Saclay, 94275 Le Kremlin Bicêtre, France Service de Psychiatrie- Hôpital Bicêtre- GH Paris Saclay- APHP, 94275 Le Kremlin Bicêtre, France Faculté de Médecine Paris-Saclay, 94275 Le Kremlin Bicêtre, France
A. Rigal
Affiliation:
INSERM CESP - Equipe ‘Moods’- Univ Paris-Saclay, 94275 Le Kremlin Bicêtre, France Service de Psychiatrie- Hôpital Bicêtre- GH Paris Saclay- APHP, 94275 Le Kremlin Bicêtre, France Faculté de Médecine Paris-Saclay, 94275 Le Kremlin Bicêtre, France
S. Martin
Affiliation:
INSERM CESP - Equipe ‘Moods’- Univ Paris-Saclay, 94275 Le Kremlin Bicêtre, France Service de Psychiatrie- Hôpital Bicêtre- GH Paris Saclay- APHP, 94275 Le Kremlin Bicêtre, France Faculté de Médecine Paris-Saclay, 94275 Le Kremlin Bicêtre, France
C. Verstuyft
Affiliation:
INSERM CESP - Equipe ‘Moods’- Univ Paris-Saclay, 94275 Le Kremlin Bicêtre, France Faculté de Médecine Paris-Saclay, 94275 Le Kremlin Bicêtre, France Service de Génétique moléculaire, Pharmacogénétique et Hormonologie- CHU de Bicêtre- APHP, 94275 Le Kremlin Bicêtre, France
B. Fève
Affiliation:
Sorbonne Université-INSERM UMR S_938, Centre de Recherche Saint-Antoine, 75012Paris, France Service d'Endocrinologie- Hôpital Saint-Antoine- APHP, 75012Paris, France Institut Hospitalo-Universitaire ICAN, 75012Paris, France
P. Chanson
Affiliation:
Faculté de Médecine Paris-Saclay, 94275 Le Kremlin Bicêtre, France Inserm U1185 - Univ Paris-Sud, 94275 Le Kremlin Bicêtre, France Service d'Endocrinologie et des Maladies de la Reproduction- CHU de Bicêtre- APHP, 94275 Le Kremlin Bicêtre, France
L. Becquemont
Affiliation:
INSERM CESP - Equipe ‘Moods’- Univ Paris-Saclay, 94275 Le Kremlin Bicêtre, France Faculté de Médecine Paris-Saclay, 94275 Le Kremlin Bicêtre, France Service de Génétique moléculaire, Pharmacogénétique et Hormonologie- CHU de Bicêtre- APHP, 94275 Le Kremlin Bicêtre, France
E. Corruble*
Affiliation:
INSERM CESP - Equipe ‘Moods’- Univ Paris-Saclay, 94275 Le Kremlin Bicêtre, France Service de Psychiatrie- Hôpital Bicêtre- GH Paris Saclay- APHP, 94275 Le Kremlin Bicêtre, France Faculté de Médecine Paris-Saclay, 94275 Le Kremlin Bicêtre, France
*
Author for correspondence: E. Corruble, E-mail: emmanuelle.corruble@aphp.fr
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Abstract

Background

Nitric oxide synthase (NOS) activity, an enzyme potentially involved in the major depressive episodes (MDE), could be indirectly measured by the L-Citrulline/L-Arginine ratio (L-Cit/L-Arg). The aim of this study was: (1) to compare the NOS activity of patients with a MDE to that of healthy controls (HC); (2) to assess its change after antidepressant treatment.

Methods

A total of 460 patients with a current MDE in a context of major depressive disorder (MDD) were compared to 895 HC for NOS activity (L-Cit/L-Arg plasma ratio). L-Arg and L-Cit plasma levels were measured using a MS-based liquid chromatography method. Depressed patients were assessed at baseline, and after 3 and 6 months of antidepressant treatment for depression severity and clinical response.

Results

Depressed patients had a lower NOS activity than HC at baseline [0.31 ± 0.09 v. 0.38 ± 0.12; 95% confidence interval (CI) −0.084 to −0.062, p < 0.0001]. Lower NOS activity at baseline predicted a higher response rate [odds ratio (OR) = 29.20; 95% CI 1.58–536.37; p = 0.023]. NOS activity in depressed patients increased significantly up to 0.34 ± 0.08 after antidepressant treatment (Est = 0.0034; 95% CI 0.0002–0.0067; p = 0.03).

Conclusions

Depressed patients have a decreased NOS activity that improves after antidepressant treatment and predicts drug response. NOS activity may be a promising biomarker for MDE in a context of MDD.

Keywords

Antidepressantbiomarkermajor depressive disordermajor depressive episodemetabolomicsnitric oxide synthase
Type
Original Article
Information
Psychological Medicine , Volume 52 , Issue 1 , January 2022 , pp. 80 - 89
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Copyright
Copyright © The Author(s), 2020. Published by Cambridge University Press

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