GPR56/ADGRG1 is associated with response to antidepressant treatment

Raoul Belzeaux; Victor Gorgievski; Laura M. Fiori; Juan Pablo Lopez; Julien Grenier; Rixing Lin; Corina Nagy; El Chérif Ibrahim; Eduardo Gascon; Philippe Courtet; Stéphane Richard-Devantoy; Marcelo Berlim; Eduardo Chachamovich; Jean François Théroux; Sylvie Dumas; Bruno Giros; Susan Rotzinger; Claudio N. Soares; Jane A. Foster; Naguib Mechawar; Gregory G. Tall; Eleni T. Tzavara; Sidney H. Kennedy; Gustavo Turecki

doi:10.1038/s41467-020-15423-5

GPR56/ADGRG1 is associated with response to antidepressant treatment

Raoul Belzeaux, Victor Gorgievski, Laura M. Fiori, Juan Pablo Lopez, Julien Grenier, Rixing Lin, Corina Nagy, El Chérif Ibrahim, Eduardo Gascon, Philippe Courtet, Stéphane Richard-Devantoy, Marcelo Berlim, Eduardo Chachamovich, Jean François Théroux, Sylvie Dumas, Bruno Giros, Susan Rotzinger, Claudio N. Soares, Jane A. Foster, Naguib MechawarGregory G. Tall, Eleni T. Tzavara, Sidney H. Kennedy, Gustavo Turecki

Research output: Contribution to journal › Article › peer-review

33 Scopus citations

Abstract

It remains unclear why many patients with depression do not respond to antidepressant treatment. In three cohorts of individuals with depression and treated with serotonin-norepinephrine reuptake inhibitor (N = 424) we show that responders, but not non-responders, display an increase of GPR56 mRNA in the blood. In a small group of subjects we also show that GPR56 is downregulated in the PFC of individuals with depression that died by suicide. In mice, we show that chronic stress-induced Gpr56 downregulation in the blood and prefrontal cortex (PFC), which is accompanied by depression-like behavior, and can be reversed by antidepressant treatment. Gpr56 knockdown in mouse PFC is associated with depressive-like behaviors, executive dysfunction and poor response to antidepressant treatment. GPR56 peptide agonists have antidepressant-like effects and upregulated AKT/GSK3/EIF4 pathways. Our findings uncover a potential role of GPR56 in antidepressant response.

Original language	English (US)
Article number	1635
Journal	Nature communications
Volume	11
Issue number	1
DOIs	https://doi.org/10.1038/s41467-020-15423-5
State	Published - Dec 1 2020
Externally published	Yes

ASJC Scopus subject areas

Physics and Astronomy(all)
Chemistry(all)
Biochemistry, Genetics and Molecular Biology(all)

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10.1038/s41467-020-15423-5

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Belzeaux, R., Gorgievski, V., Fiori, L. M., Lopez, J. P., Grenier, J., Lin, R., Nagy, C., Ibrahim, E. C., Gascon, E., Courtet, P., Richard-Devantoy, S., Berlim, M., Chachamovich, E., Théroux, J. F., Dumas, S., Giros, B., Rotzinger, S., Soares, C. N., Foster, J. A., ... Turecki, G. (2020). GPR56/ADGRG1 is associated with response to antidepressant treatment. Nature communications, 11(1), Article 1635. https://doi.org/10.1038/s41467-020-15423-5

Belzeaux, R, Gorgievski, V, Fiori, LM, Lopez, JP, Grenier, J, Lin, R, Nagy, C, Ibrahim, EC, Gascon, E, Courtet, P, Richard-Devantoy, S, Berlim, M, Chachamovich, E, Théroux, JF, Dumas, S, Giros, B, Rotzinger, S, Soares, CN, Foster, JA, Mechawar, N, Tall, GG, Tzavara, ET, Kennedy, SH & Turecki, G 2020, 'GPR56/ADGRG1 is associated with response to antidepressant treatment', Nature communications, vol. 11, no. 1, 1635. https://doi.org/10.1038/s41467-020-15423-5

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title = "GPR56/ADGRG1 is associated with response to antidepressant treatment",

abstract = "It remains unclear why many patients with depression do not respond to antidepressant treatment. In three cohorts of individuals with depression and treated with serotonin-norepinephrine reuptake inhibitor (N = 424) we show that responders, but not non-responders, display an increase of GPR56 mRNA in the blood. In a small group of subjects we also show that GPR56 is downregulated in the PFC of individuals with depression that died by suicide. In mice, we show that chronic stress-induced Gpr56 downregulation in the blood and prefrontal cortex (PFC), which is accompanied by depression-like behavior, and can be reversed by antidepressant treatment. Gpr56 knockdown in mouse PFC is associated with depressive-like behaviors, executive dysfunction and poor response to antidepressant treatment. GPR56 peptide agonists have antidepressant-like effects and upregulated AKT/GSK3/EIF4 pathways. Our findings uncover a potential role of GPR56 in antidepressant response.",

author = "Raoul Belzeaux and Victor Gorgievski and Fiori, {Laura M.} and Lopez, {Juan Pablo} and Julien Grenier and Rixing Lin and Corina Nagy and Ibrahim, {El Ch{\'e}rif} and Eduardo Gascon and Philippe Courtet and St{\'e}phane Richard-Devantoy and Marcelo Berlim and Eduardo Chachamovich and Th{\'e}roux, {Jean Fran{\c c}ois} and Sylvie Dumas and Bruno Giros and Susan Rotzinger and Soares, {Claudio N.} and Foster, {Jane A.} and Naguib Mechawar and Tall, {Gregory G.} and Tzavara, {Eleni T.} and Kennedy, {Sidney H.} and Gustavo Turecki",

note = "Funding Information: We are grateful to all patients for their involvement in this research. This manuscript contains data from four registered clinical trials: www.ClinicalTrials.gov NCT00635219, NCT00599911, NCT01140906, and NCT02209142. Clinical trials NCT00635219, NCT00599911, and NCT01140906 were sponsored by Lundbeck, and samples were provided as a donation to the Canadian Biomarker Integration Network in Depression (CAN-BIND) program. This research was conducted with the support of CAN-BIND, an Integrated Discovery Program, with funding from the Ontario Brain Institute, an independent non-profit corporation, funded partially by the Ontario government. RB received a grant from Fondamental Foundation (Post-doctoral fellowship). RB and EI were supported by the Agence Nationale de la Recherche (ANR-13-SAMA-0002). VG holds a Labex-Biopsy Fellowship. ETT is supported by Fondation de Recherche sur le Cerveau and Fondation de France. ETT is a past recipient of the Bodossakis Foundation Young Scientist Award. RB, ECI, ETT and GT were supported by ERA-NET NEURON (Grant ANTARES). GT holds a Canada Research Chair (Tier 1) and a NARSAD Distinguished Investigator Award. He is supported by grants from the Canadian Institute of Health Research (CIHR) (FDN148374 and EGM141899), and by the Fonds de recherche du Qu{\'e}bec – Sant{\'e} (FRQS) through the Quebec Network on Suicide, Mood Disorders and Related Disorders. We would like to thank ML Niepon (Institute of Vision, Paris) for slide scanning for the FISH experiments. Publisher Copyright: {\textcopyright} 2020, The Author(s).",

year = "2020",

month = dec,

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doi = "10.1038/s41467-020-15423-5",

language = "English (US)",

volume = "11",

journal = "Nature communications",

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T1 - GPR56/ADGRG1 is associated with response to antidepressant treatment

AU - Belzeaux, Raoul

AU - Gorgievski, Victor

AU - Fiori, Laura M.

AU - Lopez, Juan Pablo

AU - Grenier, Julien

AU - Lin, Rixing

AU - Nagy, Corina

AU - Ibrahim, El Chérif

AU - Gascon, Eduardo

AU - Courtet, Philippe

AU - Richard-Devantoy, Stéphane

AU - Berlim, Marcelo

AU - Chachamovich, Eduardo

AU - Théroux, Jean François

AU - Dumas, Sylvie

AU - Giros, Bruno

AU - Rotzinger, Susan

AU - Soares, Claudio N.

AU - Foster, Jane A.

AU - Mechawar, Naguib

AU - Tall, Gregory G.

AU - Tzavara, Eleni T.

AU - Kennedy, Sidney H.

AU - Turecki, Gustavo

N1 - Funding Information: We are grateful to all patients for their involvement in this research. This manuscript contains data from four registered clinical trials: www.ClinicalTrials.gov NCT00635219, NCT00599911, NCT01140906, and NCT02209142. Clinical trials NCT00635219, NCT00599911, and NCT01140906 were sponsored by Lundbeck, and samples were provided as a donation to the Canadian Biomarker Integration Network in Depression (CAN-BIND) program. This research was conducted with the support of CAN-BIND, an Integrated Discovery Program, with funding from the Ontario Brain Institute, an independent non-profit corporation, funded partially by the Ontario government. RB received a grant from Fondamental Foundation (Post-doctoral fellowship). RB and EI were supported by the Agence Nationale de la Recherche (ANR-13-SAMA-0002). VG holds a Labex-Biopsy Fellowship. ETT is supported by Fondation de Recherche sur le Cerveau and Fondation de France. ETT is a past recipient of the Bodossakis Foundation Young Scientist Award. RB, ECI, ETT and GT were supported by ERA-NET NEURON (Grant ANTARES). GT holds a Canada Research Chair (Tier 1) and a NARSAD Distinguished Investigator Award. He is supported by grants from the Canadian Institute of Health Research (CIHR) (FDN148374 and EGM141899), and by the Fonds de recherche du Québec – Santé (FRQS) through the Quebec Network on Suicide, Mood Disorders and Related Disorders. We would like to thank ML Niepon (Institute of Vision, Paris) for slide scanning for the FISH experiments. Publisher Copyright: © 2020, The Author(s).

PY - 2020/12/1

Y1 - 2020/12/1

N2 - It remains unclear why many patients with depression do not respond to antidepressant treatment. In three cohorts of individuals with depression and treated with serotonin-norepinephrine reuptake inhibitor (N = 424) we show that responders, but not non-responders, display an increase of GPR56 mRNA in the blood. In a small group of subjects we also show that GPR56 is downregulated in the PFC of individuals with depression that died by suicide. In mice, we show that chronic stress-induced Gpr56 downregulation in the blood and prefrontal cortex (PFC), which is accompanied by depression-like behavior, and can be reversed by antidepressant treatment. Gpr56 knockdown in mouse PFC is associated with depressive-like behaviors, executive dysfunction and poor response to antidepressant treatment. GPR56 peptide agonists have antidepressant-like effects and upregulated AKT/GSK3/EIF4 pathways. Our findings uncover a potential role of GPR56 in antidepressant response.

AB - It remains unclear why many patients with depression do not respond to antidepressant treatment. In three cohorts of individuals with depression and treated with serotonin-norepinephrine reuptake inhibitor (N = 424) we show that responders, but not non-responders, display an increase of GPR56 mRNA in the blood. In a small group of subjects we also show that GPR56 is downregulated in the PFC of individuals with depression that died by suicide. In mice, we show that chronic stress-induced Gpr56 downregulation in the blood and prefrontal cortex (PFC), which is accompanied by depression-like behavior, and can be reversed by antidepressant treatment. Gpr56 knockdown in mouse PFC is associated with depressive-like behaviors, executive dysfunction and poor response to antidepressant treatment. GPR56 peptide agonists have antidepressant-like effects and upregulated AKT/GSK3/EIF4 pathways. Our findings uncover a potential role of GPR56 in antidepressant response.

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GPR56/ADGRG1 is associated with response to antidepressant treatment

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