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Depression and the Glutamate/GABA-Glutamine Cycle

2024· review· en· W4401644336 on OpenAlex

Why this work is in the frame

A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.

affAt least one author lists a Canadian institution in the pinned OpenAlex snapshot.

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.

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)0.001
metaresearch head score (Gemma)0.001
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesMeta-epidemiology (narrow), Science and technology studies, Research integrity, Insufficient payload (model declined to judge)
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Not applicable · Consensus signal: none
GenreCandidate signal: Review · Consensus signal: Review
Teacher disagreement score0.983
Threshold uncertainty score1.000

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0010.001
Meta-epidemiology (narrow)0.0010.001
Meta-epidemiology (broad)0.0020.001
Bibliometrics0.0010.002
Science and technology studies0.0010.003
Scholarly communication0.0000.000
Open science0.0020.002
Research integrity0.0000.004
Insufficient payload (model declined to judge)0.0000.002

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