Investigating the disturbance in cortical glutamate and GABA function in psychosis and its origins and consequences
Bibliographic record
Abstract
We investigated the longstanding idea that the onset of psychotic symptoms in schizophrenia arises from an early phase of glutamate neurotoxicity, possibly related to loss of GABA restraint, oxidative stress or inflammation, that cumulatively results in a later phase of synaptic loss in keeping with magnetic resonance spectroscopy (MRS) evidence of reduced glutamate in schizophrenia, especially in older patients. We evaluated this hypothesis in a 3-centre MRS study to determine whether abnormalities in glutamate in dorsal anterior cingulate cortex (dACC) differed between people with minimally treated 'Recent' onset schizophrenia and an 'Established' group with > 10 years of illness. We tested the hypothesised mechanisms of reduced GABA in either or both dACC and occipital cortex, and depletion of dACC glutathione, a measure of central inflammation. We explored predicted associations between MRS variables, circulating cytokines and clinical symptoms. The Established group showed significantly greater dACC glutamate deficit than the Recent group which was not accounted for by lifetime exposure to antipsychotic drugs or by their greater CRP or IL-6 levels nor was the deficit associated with glutathione depletion. The greater dACC glutamate deficit in established illness is compatible with loss of synapses occurring after onset of symptoms but there was little to suggest underpinning excitotoxicity, inflammation, or oxidative stress. GABA was reduced in patients versus controls across dACC and occipital voxels. Only dACC GABA content correlated significantly with symptoms, lower content with greater positive and negative symptoms across both groups and this is supportive of a pathophysiological role of GABA in psychosis.
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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 | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
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.
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".