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Depression and the Glutamate/GABA-Glutamine Cycle

2024· review· en· W4401644336 on OpenAlexaff
Mortimer Mamelak

Bibliographic record

VenueCurrent Neuropharmacology · 2024
Typereview
Languageen
FieldNeuroscience
TopicNeuroscience and Neuropharmacology Research
Canadian institutionsBaycrest HospitalUniversity of Toronto
Fundersnot available
KeywordsGlutamate receptorGlutamineNeurotransmissionCholinergicMetabotropic glutamate receptorNeurosciencePharmacologyEndocrinologyInternal medicineMedicineChemistryBiologyBiochemistryAmino acidReceptor

Abstract

fetched live from OpenAlex

Many features of major depressive disorder are mirrored in rodent models of psychological stress. These models have been used to examine the relationship between the activation of the hypothalamic- pituitary axis in response to stress, the development of oxidative stress and neuroinflammation, the dominance of cholinergic neurotransmission and the associated increase in REM sleep pressure. Rodent models have also provided valuable insights into the impairment of glycolysis and brain glucose utilization by the brain under stress, the resulting decrease in brain energy production and the reduction in glutamate/GABA-glutamine cycling. The rapidly acting antidepressants, scopolamine, ketamine and ECT, all raise extracellular glutamate and scopolamine and ketamine have specifically been shown to increase glutamate/GABA-glutamine cycling in men and rodents with corresponding short-term relief of depression. The nightly use of gammahydroxybutyrate (GHB) may achieve more permanent results and may even act prophylactically to prevent the development or recurrence of depression. GHB is a GABAB agonist and restores the normal balance between cholinergic and monoaminergic neurotransmission by inhibiting cholinergic neurotransmission. It relieves REM sleep pressure. GHB's metabolism generates NADPH, a key antioxidant cofactor. Its metabolism also generates succinate, the tricarboxylic acid cycle intermediate, to provide energy to the cell and to synthesize glutamate. In both animals and man, GHB increases the level of brain glutamate.

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)0.000
metaresearch head score (Gemma)0.000
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Not applicable · Consensus signal: none
GenreCandidate signal: Review · Consensus signal: Review
Teacher disagreement score0.002
Threshold uncertainty score0.008

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0010.000
Meta-epidemiology (broad)0.0010.000
Bibliometrics0.0020.002
Science and technology studies0.0000.001
Scholarly communication0.0010.001
Open science0.0010.001
Research integrity0.0010.002
Insufficient payload (model declined to judge)0.0020.003

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 head0.116
GPT teacher head0.451
Teacher spread0.336 · 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 designNot applicable
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

Citations24
Published2024
Admission routes1
Has abstractyes

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