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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
Nature communications | 2020

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.

Pubmed ID: 32242018

Associated grants

  • Agency: NIGMS NIH HHS, United States
    Id: R01 GM120110
  • Agency: NINDS NIH HHS, United States
    Id: R01 NS103946
  • Agency: CIHR, Canada
    Id: FDN148374
  • Agency: CIHR, Canada
    Id: EGM141899

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This is a list of tools and resources that we have found mentioned in this publication.


ATCC (tool)

RRID:SCR_001672

Global nonprofit biological resource center (BRC) and research organization that provides biological products, technical services and educational programs to private industry, government and academic organizations. Its mission is to acquire, authenticate, preserve, develop and distribute biological materials, information, technology, intellectual property and standards for the advancement and application of scientific knowledge. The primary purpose of ATCC is to use its resources and experience as a BRC to become the world leader in standard biological reference materials management, intellectual property resource management and translational research as applied to biomaterial development, standardization and certification. ATCC characterizes cell lines, bacteria, viruses, fungi and protozoa, as well as develops and evaluates assays and techniques for validating research resources and preserving and distributing biological materials to the public and private sector research communities.

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ClinicalTrials.gov (tool)

RRID:SCR_002309

Registry and results database of federally and privately supported clinical trials conducted in United States and around world. Provides information about purpose of trial, who may participate, locations, and phone numbers for more details. This information should be used in conjunction with advice from health care professionals.Offers information for locating federally and privately supported clinical trials for wide range of diseases and conditions. Research study in human volunteers to answer specific health questions. Interventional trials determine whether experimental treatments or new ways of using known therapies are safe and effective under controlled environments. Observational trials address health issues in large groups of people or populations in natural settings. ClinicalTrials.gov contains trials sponsored by National Institutes of Health, other federal agencies, and private industry. Studies listed in database are conducted in all 50 States and in 178 countries.

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Ensembl (tool)

RRID:SCR_002344

Collection of genome databases for vertebrates and other eukaryotic species with DNA and protein sequence search capabilities. Used to automatically annotate genome, integrate this annotation with other available biological data and make data publicly available via web. Ensembl tools include BLAST, BLAT, BioMart and the Variant Effect Predictor (VEP) for all supported species.

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Applied Biosystems (tool)

RRID:SCR_005039

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LIMMA (tool)

RRID:SCR_010943

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Trimmomatic (tool)

RRID:SCR_011848

Software Java pipeline for trimming tasks for Illumina paired end and single ended data. Flexible Trimmer for Illumina Sequence Data. Pair aware preprocessing tool optimized for Illumina next generation sequencing data. Includes several processing steps for read trimming and filtering. Operating systems Unix/Linux, Mac OS, Windows.

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htseq-count (tool)

RRID:SCR_011867

Script distributed with the HT-Seq Python framework for processing RNA-seq or DNA-seq data.

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TopHat (tool)

RRID:SCR_013035

Software tool for fast and high throughput alignment of shotgun cDNA sequencing reads generated by transcriptomics technologies. Fast splice junction mapper for RNA-Seq reads. Aligns RNA-Seq reads to mammalian-sized genomes using ultra high-throughput short read aligner Bowtie, and then analyzes mapping results to identify splice junctions between exons.TopHat2 is accurate alignment of transcriptomes in presence of insertions, deletions and gene fusions.

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DESeq2 (tool)

RRID:SCR_015687

Software package for differential gene expression analysis based on the negative binomial distribution. Used for analyzing RNA-seq data for differential analysis of count data, using shrinkage estimation for dispersions and fold changes to improve stability and interpretability of estimates.

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SK-N-AS (tool)

RRID:CVCL_1700

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BALB/cAnNCrl (tool)

RRID:MGI:2683685

laboratory mouse with name BALB/cAnNCrl from MGI.

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C57BL/6J (tool)

RRID:IMSR_JAX:000664

Mus musculus with name C57BL/6J from IMSR.

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