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

35 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

General Physics and Astronomy
General Chemistry
General Biochemistry, Genetics and Molecular Biology

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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",

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AU - Gorgievski, Victor

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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

PY - 2020/12/1

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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.

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GPR56/ADGRG1 is associated with response to antidepressant treatment

Abstract

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