The GG genotype of the serotonin 4 receptor genetic polymorphism, rs1345697, is associated with lower remission rates after antidepressant treatment: Findings from the METADAP cohort.

Autor: Poinsignon V; MOODS Team, CESP, INSERM, Faculté de médecine, Université Paris-Saclay, Le Kremlin Bicêtre, F-94275 France; Service de Génétique Moléculaire, Pharmacogénétique et Hormonologie de Bicêtre, Hôpitaux Universitaires Paris-Saclay, Assistance Publique-Hôpitaux de Paris, Hôpital de Bicêtre, Le Kremlin Bicêtre, F-94275 France., Colle R; MOODS Team, CESP, INSERM, Faculté de médecine, Université Paris-Saclay, Le Kremlin Bicêtre, F-94275 France; Service Hospitalo-Universitaire de Psychiatrie de Bicêtre, Hôpitaux Universitaires Paris-Saclay, Assistance Publique-Hôpitaux de Paris, Hôpital de Bicêtre, Le Kremlin Bicêtre, F-94275 France., Asmar KE; MOODS Team, CESP, INSERM, Faculté de médecine, Université Paris-Saclay, Le Kremlin Bicêtre, F-94275 France; Department of Epidemiology and Population Health, American University of Beirut, Beirut 1107 2020 Leban., Mendez-David I; MOODS Team, CESP, INSERM, Faculté de Pharmacie, INSERM, Université Paris-Saclay, Châtenay-Malabry, France., David DJ; MOODS Team, CESP, INSERM, Faculté de Pharmacie, INSERM, Université Paris-Saclay, Châtenay-Malabry, France., Ait Tayeb AEK; MOODS Team, CESP, INSERM, Faculté de médecine, Université Paris-Saclay, Le Kremlin Bicêtre, F-94275 France; Service Hospitalo-Universitaire de Psychiatrie de Bicêtre, Hôpitaux Universitaires Paris-Saclay, Assistance Publique-Hôpitaux de Paris, Hôpital de Bicêtre, Le Kremlin Bicêtre, F-94275 France., Chappell K; MOODS Team, CESP, INSERM, Faculté de médecine, Université Paris-Saclay, Le Kremlin Bicêtre, F-94275 France., Gressier F; MOODS Team, CESP, INSERM, Faculté de médecine, Université Paris-Saclay, Le Kremlin Bicêtre, F-94275 France; Service Hospitalo-Universitaire de Psychiatrie de Bicêtre, Hôpitaux Universitaires Paris-Saclay, Assistance Publique-Hôpitaux de Paris, Hôpital de Bicêtre, Le Kremlin Bicêtre, F-94275 France., Herrero H; Service Hospitalo-Universitaire de Psychiatrie de Bicêtre, Hôpitaux Universitaires Paris-Saclay, Assistance Publique-Hôpitaux de Paris, Hôpital de Bicêtre, Le Kremlin Bicêtre, F-94275 France., Fève B; Centre de Recherche Saint-Antoine, UMR_S938, Sorbonne Université-Inserm Equipe 'Lipodystrophies, adaptations métaboliques et hormonales, et vieillissement', Service d'Endocrinologie, Hôpital Saint-Antoine, Assistance Publique-Hôpitaux de Paris, Paris, F-75012 France., Becquemont L; MOODS Team, CESP, INSERM, Faculté de médecine, Université Paris-Saclay, Le Kremlin Bicêtre, F-94275 France., Corruble E; MOODS Team, CESP, INSERM, Faculté de médecine, Université Paris-Saclay, Le Kremlin Bicêtre, F-94275 France; Service Hospitalo-Universitaire de Psychiatrie de Bicêtre, Hôpitaux Universitaires Paris-Saclay, Assistance Publique-Hôpitaux de Paris, Hôpital de Bicêtre, Le Kremlin Bicêtre, F-94275 France., Verstuyft C; MOODS Team, CESP, INSERM, Faculté de médecine, Université Paris-Saclay, Le Kremlin Bicêtre, F-94275 France; Service de Génétique Moléculaire, Pharmacogénétique et Hormonologie de Bicêtre, Hôpitaux Universitaires Paris-Saclay, Assistance Publique-Hôpitaux de Paris, Hôpital de Bicêtre, Le Kremlin Bicêtre, F-94275 France. Electronic address: celine.verstuyft@aphp.fr.
Jazyk: angličtina
Zdroj: Journal of affective disorders [J Affect Disord] 2022 Feb 15; Vol. 299, pp. 335-343. Date of Electronic Publication: 2021 Dec 11.
DOI: 10.1016/j.jad.2021.12.012
Abstrakt: Background: Pharmacological studies have yielded valuable insights into the role of the serotonin 4 receptor (HTR4) in major depressive episodes (MDE) and response to antidepressant drugs (AD). A genetic association has been shown between HTR4 and susceptibility to mood disorders. Our study aims at assessing the association between the HTR4 genetic polymorphism, rs1345697, and improvement in depressive symptoms and remission after antidepressant treatment in MDE patients.
Methods: 492 depressed patients from the METADAP cohort were treated prospectively for 6 months with ADs. The clinical outcomes according to HTR4 rs1345697 were compared after 1 (M1), 3 (M3), and 6 (M6) months of treatment. Mixed-effects logistic regression and adjusted linear models assessed the association between rs1345697 and 17-item Hamilton Depression Rating Scale (HDRS) score improvement and response/remission.
Results: Over the 6 months of treatment, mixed-effects regressions showed lower improvements in HDRS scores (Coefficient=1.52; Confident Interval (CI) 95% [0.37-2.67]; p = 0.009) and lower remission rates (Odds Ratio=2.0; CI95% [1.0-4.1]; p = 0.05) in GG homozygous patients as compared to allele A carriers.
Limitations: The major limitations of our study are the uncertainty of the rs1345697 effect on HTR4 function, the substantial drop-out rate, and the fact that analysis is not based on randomization between polymorphism groups.
Conclusions: In our study, patients who were homozygous carriers of the variant G of the HTR4 rs1345697 had lower depressive symptoms improvement and 2-fold lower remission rates after antidepressant treatment as compared to allele A carriers. Randomization study should be done to confirm these results.
(Copyright © 2021. Published by Elsevier B.V.)
Databáze: MEDLINE
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