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Record W3014619333 · doi:10.1038/s41467-020-15423-5

GPR56/ADGRG1 is associated with response to antidepressant treatment

2020· article· en· W3014619333 on OpenAlexafffund
Raoul Belzeaux, Victor Gorgievski, Laura M. Fiori, Juan Pablo López, Julien Grenier, Rixing Lin, Corina Nagy, El Chérif Ibrahim, Eduardo Gascon, Philippe Courtet, Stéphane Richard‐Devantoy, Marcelo T. Berlim, Eduardo Chachamovich, Jean‐François Théroux, Sylvie Dumas, Bruno Giros, Susan Rotzinger, Cláudio N. Soares, Jane A. Foster, Naguib Mechawar, Gregory G. Tall, Eleni T. Tzavara, Sidney H. Kennedy, Gustavo Turecki

Bibliographic record

VenueNature Communications · 2020
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicReceptor Mechanisms and Signaling
Canadian institutionsQueen's UniversitySt. Michael's HospitalUniversity of TorontoUniversity Health NetworkMcGill UniversityDouglas Mental Health University Institute
FundersCanadian Institutes of Health ResearchFonds de Recherche du Québec - SantéFondation de FranceGovernment of OntarioAgence Nationale de la RechercheH. Lundbeck A/SGovernment of CanadaNational Alliance for Research on Schizophrenia and DepressionNational Institute of Neurological Disorders and StrokeNational Institute of General Medical SciencesOntario Brain Institute
KeywordsAntidepressantDownregulation and upregulationNorepinephrineDepression (economics)Prefrontal cortexGene knockdownSerotoninInternal medicineEndocrinologyReuptake inhibitorMedicinePsychologyPharmacologyHippocampusNeuroscienceReceptorChemistryDopamineApoptosisGene

Abstract

fetched live from OpenAlex

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.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.551
Threshold uncertainty score0.372

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0000.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.023
GPT teacher head0.290
Teacher spread0.267 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one teacher head, not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designBench or experimental
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations65
Published2020
Admission routes2
Has abstractyes

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