Review: NMDA Receptor Hypofunction and Its Involvement in Excitotoxicity in Schizophrenia
Bibliographic record
Abstract
Schizophrenia is a severely debilitating psychiatric condition that has long been associated with altered neurotransmission in the brain, especially in dopaminergic transmission. The dopamine hypothesis of schizophrenia, while it has been the main focus of research in the past decades, fails to explain the underlying pathogenesis. A more recent hypothesis dealing with altered central glutamate signaling in schizophrenia may help to ameliorate the deficit in understanding. Blockade of the glutamatergic NMDA receptors produces schizophrenic behaviours and phenotypes almost indistinguishable from the disease itself in animal and human models. It has been elucidated that hypofunction of NMDA receptors on the parvalbumin-‐containing interneurons in the cortex and subcortical regions leads to a downstream increase in cortical glutamate release, which may be causing functional connectivity issues through mechanisms of excitotoxicity. A number of studies have pointed to the hypofunction of these NMDA receptors leading to excitotoxicity and cellular degeneration, which may be implicated in the disease pathology. This review will evaluate and highlight this forthcoming evidence.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot 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.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.002 | 0.000 |
| Bibliometrics | 0.003 | 0.004 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.002 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.005 | 0.003 |
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.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
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".