Developmental dysregulation of the cortical reelin signalling pathway precedes adolescent cognitive deficits in a neurodevelopmental model for schizophrenia
Bibliographic record
Abstract
Ketamine is a very cheap, potent, drug with proven potent antidepressant action in patients with otherwise treatment resistant depression.It causes acute dissociative symptoms when administered parenterally.As a generic, legal, 'non-natural' drug which has addiction potential and does not hit the salience network, advocacy for its use has been less vociferous than for 5HT2a psychedelics.Oxford Health NH Trust's Interventional Psychiatry Service grew out its ECT service and now administers IV ketamine 5 days a week in private (3 days) and NHS (2 days) streams to 9 patients daily.The presence of anaesthetists for the ECT service facilitated the transition to a psychiatrist led ketamine service.Staffing is typically a doctor, a nurse and a healthcare assistant, with a minimum of a doctor and an HCA.Safe, long-term administration is possible but, given the chronic/episodic nature of depression, it is not surprising that repeated administration is needed to maintain the benefit.Relapse does, of course, sometimes occur despite continued use: the social losses in chronic depression are powerful maintaining factors.However, the tolerance which sometimes develops is usually manageable with dose and frequency adjustment.Chronic depression is often complicated by changes in patterns of relationships; unlearning these take time.Two recent phase 3 RCTs suggest that ketamine causes fewer long term side effects than, and may be as effective as ECT particularly in those under 50 (Ekstrand et al 2022; Anand et al 2023).In both studies, effect sizes are affected by differential dropout.A third large pragmatic long term study is underway (NCT03674671).Post-Brexit, the MHRA, NICE and NHS have developed a new mechanism for repurposing drugs (https://www.england.nhs.uk/medicines-2/medicines-repurposing-programme/).IV racemic ketamine, at a dose of 0.5mg/kg, would be a strong candidate for licensure under this scheme.It is likely to be cost-effective as an alternative to ECT in the NHS.Routine administration of IV ketamine in the NHS is feasible using the existing ECT services, though it is likely that such services would need to expand.Experience with ketamine will also help the NHS develop the infrastructure, processes and safeguards necessary for the acceptance into NHS practice of other psychedelics.
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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) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 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 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 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".