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Record W4410755535 · doi:10.1017/s1092852925100278

Should glutamatergic modulators be considered preferential treatments for adults with major depressive disorder and a reported history of trauma? Conceptual and clinical implications

2025· review· en· W4410755535 on OpenAlexafffund
Kayla M. Teopiz, Heidi Ka Ying Lo, Moiz Lakhani, Angela T.H. Kwan, Poh Khuen Lim, M Zhang, Sabrina Wong, Gia Han Le, Jennifer Swainson, Bing Cao, Christine E. Dri, Roger Ho, Kyle Valentino, Roger S. McIntyre

Bibliographic record

VenueCNS Spectrums · 2025
Typereview
Languageen
FieldMedicine
TopicTreatment of Major Depression
Canadian institutionsUniversity of AlbertaUniversity of OttawaBrain and Cognition Discovery FoundationUniversity of Toronto
FundersBausch HealthH. Lundbeck A/SNational Natural Science Foundation of ChinaEisaiPurdue UniversityIdorsia PharmaceuticalsBiogenCanadian Institutes of Health ResearchSunovionNovo NordiskSanofiPfizer
KeywordsGlutamatergicMajor depressive disorderMedicineClinical psychologyPsychologyInternal medicineMoodGlutamate receptor

Abstract

fetched live from OpenAlex

Major depressive disorder (MDD) is a chronic, highly prevalent, and debilitating mental disorder associated with significant illness and economic burden globally. Exposure to trauma (eg, physical, sexual, emotional abuse, and/or physical, and emotional neglect) is common among individuals with MDD. Persons with MDD and a history of trauma often exhibit an attenuated response to conventional serotonergic antidepressants compared to those with non-traumatized depression. Emerging evidence indicates that exposure to trauma is associated with increased inflammatory markers [eg, C-reactive protein (CRP), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α)] as well as glutamatergic dysregulation in the central nervous system (CNS). It is hypothesized that individuals with MDD and a history of trauma may be conceptualized as a distinct bio-phenotype compared to non-traumatized depression. Furthermore, preliminary evidence positions select glutamatergic modulators as potential, novel, mechanistically-informed therapeutic strategies that may provide benefit to persons with elevated inflammation and glutamatergic dysregulation.

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 machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.001
metaresearch head score (Gemma)0.002
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Theoretical or conceptual · Consensus signal: none
GenreCandidate signal: Review · Consensus signal: Review
Teacher disagreement score0.003
Threshold uncertainty score0.010

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0010.002
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0010.001
Bibliometrics0.0010.001
Science and technology studies0.0000.000
Scholarly communication0.0010.001
Open science0.0010.000
Research integrity0.0020.002
Insufficient payload (model declined to judge)0.0030.001

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 head0.102
GPT teacher head0.377
Teacher spread0.276 · 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 source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designTheoretical or conceptual
Domainnot available
GenreReview

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

Citations4
Published2025
Admission routes2
Has abstractyes

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