Acute subanesthetic ketamine-induced effects on the mismatch negativity and their relationship to early and sustained treatment response in major depressive disorder
Bibliographic record
Abstract
BACKGROUND: A sub-anesthetic dose of ketamine, an N-methyl-D-aspartate receptor (NMDAR) antagonist, produces robust antidepressant effects in treatment-resistant major depressive disorder (MDD). The mismatch negativity (MMN) is reliant on glutamatergic neurotransmission and reduced by NMDAR antagonists. The MMN may characterise the neural mechanisms underlying ketamine's effects. AIMS: This study examined the acute effects of ketamine and midazolam on the MMN and its relationship to early and sustained decreases in depressive symptoms. METHODS: = 24), enrolled in a multi-phase clinical ketamine trial, received two intravenous infusions within an initial double-blind crossover phase: ketamine (0.5 mg/kg) and midazolam (30 μg/kg). Three recordings were carried out per session (pre-, immediately post- and 2 h post-infusion). Peak MMN amplitude (μV), latency (ms), theta event-related oscillations (EROs), theta phase locking factor (PLF) and source-localised MMN generator activity were assessed. Relationships between changes in MMN indices and early (Phase 1: double-blind, cross-over phase) and sustained (Phases 2, 3: open-label repeated and maintenance phases, respectively) changes in depressive symptoms (Montgomery-Åsberg Depression Rating Scale score) were examined. RESULTS: Ketamine reduced frontal MMN amplitudes, theta ERO immediately post- and 2 h post-infusion and source-localised peak MMN frontal generator activity. Select baseline and ketamine-induced MMN decreases correlated and predicted greater early (left frontal MMN decreases in amplitude and theta ERO, baseline left PLF) and sustained (baseline left PLF, right inferior temporal activity) symptom reductions. CONCLUSIONS: Acute NMDARs blockade reduced frontal MMN, with larger MMN reductions predicting greater symptom improvement. The MMN may serve as a non-invasive biomarker predicting antidepressant response to glutamatergic agents.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot 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.
Codex and Gemma teacher scores by category
| 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 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 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 teacher head, 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".