The ERICH3 rs11580409 polymorphism is associated with 6-month antidepressant response in depressed patients

Kenneth Chappell; Romain Colle; Abd El Kader Ait Tayeb; Jérôme Bouligand; Khalil El-Asmar; Eric Deflesselle; Bruno Fève; Laurent Becquemont; Emmanuelle Corruble; Céline Verstuyft

doi:10.1016/j.pnpbp.2022.110608

The ERICH3 rs11580409 polymorphism is associated with 6-month antidepressant response in depressed patients

Prog Neuropsychopharmacol Biol Psychiatry. 2022 Dec 20:119:110608. doi: 10.1016/j.pnpbp.2022.110608. Epub 2022 Jul 22.

Affiliations

¹ CESP, MOODS Team, INSERM UMR 1018, Faculté de Médecine, Univ Paris-Saclay, Le Kremlin Bicêtre F-94275, France. Electronic address: kenneth.chappell@universite-paris-saclay.fr.
² CESP, MOODS Team, INSERM UMR 1018, Faculté de Médecine, Univ 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.
³ 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; Plateforme d'Expertises Maladies Rares Paris-Saclay, Assistance Publique-Hôpitaux de Paris (AP-HP), France; Université Paris-Saclay, Faculté de Médecine, Unité Inserm UMRS 1185, Physiologie et Physiopathologie Endocriniennes, 94276 Le Kremlin-Bicêtre, France.
⁴ CESP, MOODS Team, INSERM UMR 1018, Faculté de Médecine, Univ Paris-Saclay, Le Kremlin Bicêtre F-94275, France; Department of Epidemiology and Population Health, Faculty of Health Sciences, American University of Beirut, Beirut, Lebanon.
⁵ CESP, MOODS Team, INSERM UMR 1018, Faculté de Médecine, Univ Paris-Saclay, Le Kremlin Bicêtre F-94275, France.
⁶ Sorbonne Université-INSERM, Centre de Recherche Saint-Antoine, Institut Hospitalo-Universitaire ICAN, Service d'Endocrinologie, CRMR PRISIS, Hôpital Saint-Antoine, Assistance Publique-Hôpitaux de Paris, Paris F-75012, France.
⁷ CESP, MOODS Team, INSERM UMR 1018, Faculté de Médecine, Univ Paris-Saclay, Le Kremlin Bicêtre F-94275, France; Centre de recherche clinique, Hôpitaux Universitaires Paris-Saclay, Assistance Publique-Hôpitaux de Paris, Hôpital de Bicêtre, Le Kremlin Bicêtre F-94275, France.
⁸ CESP, MOODS Team, INSERM UMR 1018, Faculté de Médecine, Univ 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.

PMID: 35878676
DOI: 10.1016/j.pnpbp.2022.110608

Abstract

Introduction: Major Depressive Disorder (MDD) is the current leading cause of disability worldwide. The effect of its main treatment option, antidepressant drugs (AD), is influenced by genetic and metabolic factors. The ERICH3 rs11580409(A > C) genetic polymorphism was identified as a factor influencing serotonin (5HT) levels in a pharmacometabolomics-informed genome-wide association study. It was also associated with response following AD treatment in several cohorts of depressed patients.

Objective: Our aim was to analyze the association of the ERICH3 rs11580409(A > C) genetic polymorphism with response following AD treatment and plasma 5HT levels in METADAP, a cohort of 6-month AD-treated depressed patients.

Methods: Clinical (n = 377) and metabolic (n = 150) data were obtained at baseline and after 3 (M3) and 6 months (M6) of treatment. Linear mixed-effects models and generalized logistic mixed-effects models were used to assess the association of the rs11580409 polymorphism with the Hamilton Depression Rating Scale (HDRS) score, response and remission rates, and plasma 5HT levels.

Results: The interaction between the ERICH3 rs11580409 polymorphism and time was an overall significant factor in mixed-effects models of the HDRS score (F_3,870 = 3.35, P = 0.019). At M6, CC homozygotes had a significantly lower HDRS score compared to A allele carriers (coefficient = -3.50, 95%CI [-6.00--0.99], P = 0.019). No association between rs11580409 and 5HT levels was observed.

Conclusion: Our results suggest an association of rs11580409 with response following long-term AD treatment. The rs11580409 genetic polymorphism may be a useful biomarker for treatment response in major depression.

Trial registration: ClinicalTrials.gov NCT00526383.

Keywords: Antidepressant; ERICH3; Major depressive disorder; Pharmacogenetics; Serotonin.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Antidepressive Agents / therapeutic use
Depressive Disorder, Major* / drug therapy
Depressive Disorder, Major* / genetics
Genome-Wide Association Study
Humans
Polymorphism, Genetic / genetics
Selective Serotonin Reuptake Inhibitors / therapeutic use
Serotonin
Treatment Outcome

Substances

Antidepressive Agents
Serotonin Uptake Inhibitors
Serotonin

Associated data

ClinicalTrials.gov/NCT00526383