688. TEMPORAL IMMUNE EFFECTS OF ORAL KETAMINE ON PTSD: TRANSCRIPTOMIC EVIDENCE OF SHORT-TERM INFLAMMATION SUPPRESSION AND LONG-TERM IMMUNE REMODELLING
Bibliographic record
Abstract
Abstract Background Ketamine has emerged as a promising rapid-acting treatment for post-traumatic stress disorder (PTSD), offering swift symptom relief. However, the molecular mechanisms underpinning its long-term therapeutic effects remain poorly understood. Aims & Objectives This study aimed to investigate the short- and long-term gene expression changes following oral ketamine treatment in individuals with PTSD. It was hypothesised that ketamine would induce time-dependent transcriptional changes, shifting from acute immune suppression to long-term immune modulation and tissue repair. Method Twenty-three individuals with PTSD (9 males, 14 females) participated in a six-week trial involving subanesthetic doses of oral ketamine. Peripheral blood mononuclear cells (PBMCs) were collected at baseline, one week (short-term), and four weeks (long-term) post-treatment. RNA sequencing and transcriptome-wide analysis were conducted to assess differential gene expression and pathway activity across timepoints. Results Analysis identified 533 up-regulated and 621 down-regulated genes across timepoints. A 37% increase in gene expression changes was observed from short- to long-term, along with a 6.5-fold increase in expression magnitude and an 8.8-fold rise in pathway activation. Key modulated pathways included interferon alpha/beta signalling (z = 4), IL-17 signalling (z = 3.36), cytokine storm (z = 4.26), neutrophil degranulation (z = 6.0), and antimicrobial peptide signalling (z = 1.63). Notable gene-level regulators included IL-6, IL-1β, IFI27, CXCL8, SOCS1/3, IL-10, and CAMP. Discussion & Conclusions Findings demonstrate that ketamine induces distinct temporal molecular changes, transitioning from short-term inflammation suppression and antimicrobial responses to long-term immune remodulation and tissue repair. These results provide critical insight into the prolonged therapeutic mechanisms of ketamine in PTSD and support the development of personalised maintenance strategies to sustain clinical benefit and prevent relapse.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.002 | 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".