The effect of exogenous ketones on signs and symptoms of schizophrenia spectrum and bipolar disorders: study protocol for a triple-blind, randomized, controlled cross-over pilot study
Bibliographic record
Abstract
Abstract Introduction Inflammation, oxidative stress, and bioenergetic dysfunction are proposed underlying mechanisms of schizophrenia spectrum disorders (SSD) and bipolar disorders (BD), contributing to the largely untreated cognitive and negative symptoms in these conditions. Ketone bodies may offer a therapeutic option for these symptoms through their positive effects on the aforementioned mechanisms. Exogenous ketones like ketone esters (KE) provide a means to quickly induce ketosis without dietary restrictions, though their effects on SSD and BD have not yet been investigated. Here, we describe the study protocol of an ongoing triple-blind, randomized controlled crossover trial on the effects of a single ingestion of KE on signs and symptoms of SSD and BD. Methods A total of 24 patients (12 SSD, 12 BD) receiving inpatient care at Amsterdam UMC will be included in the study. Patients will ingest a single dose of KE ((R)-3-hydroxybutyl-(R)-3-hydroxybutyrate deltaG® ketones - dGK) and an isocaloric carbohydrate control with a washout period of three days between drinks. The primary outcome is the change in pre-pulse inhibition of the startle reflex (PPI) induced by dGK ingestion compared to control. Secondary outcomes include resting-state EEG, P3B amplitude, cognitive performance, and metabolic, immune, oxidative stress and circadian rhythm parameters. Feasibility and potential side effects will also be assessed. Discussion Our current study offers valuable preliminary data on the effects of KE in SSD and BD patients. It can provide the foundation for future research into the therapeutic potential of KE in alleviating symptoms and improving functional outcomes in these disorders. Trial registration www.ClinicalTrials.gov , ID: NCT06426134 .
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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 | 0.019 | 0.012 |
| Meta-epidemiology (narrow) | 0.005 | 0.003 |
| Meta-epidemiology (broad) | 0.011 | 0.003 |
| Bibliometrics | 0.002 | 0.002 |
| Science and technology studies | 0.003 | 0.003 |
| Scholarly communication | 0.002 | 0.002 |
| Open science | 0.003 | 0.001 |
| Research integrity | 0.005 | 0.005 |
| Insufficient payload (model declined to judge) | 0.034 | 0.009 |
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".