• Temporal immune effects of Ora...

Treffer: Temporal immune effects of Oral ketamine on PTSD: Transcriptomic evidence of short-term inflammation suppression and sustained immune Remodelling.

Title:
Temporal immune effects of Oral ketamine on PTSD: Transcriptomic evidence of short-term inflammation suppression and sustained immune Remodelling.
Authors:
Wellington NJ; National PTSD Research Centre, Thompson Institute, University of the Sunshine Coast (UniSC), Birtinya, QLD, Australia; School of Health, UniSC, Sippy Downs, QLD, Australia; Centre for Bioinnovation, UniSC, Sippy Downs, QLD, Australia; Thompson Brain and Mind Healthcare, PO Box 1544, Sunshine Plaza, QLD, 4558, Australia; Sunshine Coast Health Institute, Sunshine Coast Hospital and Health Service, Birtinya, QLD, 4575, Australia. Electronic address: nwellington@tbmh.org.au., Quigley BL; National PTSD Research Centre, Thompson Institute, University of the Sunshine Coast (UniSC), Birtinya, QLD, Australia; Centre for Bioinnovation, UniSC, Sippy Downs, QLD, Australia; Sunshine Coast Health Institute, Sunshine Coast Hospital and Health Service, Birtinya, QLD, 4575, Australia., Bouças AP; National PTSD Research Centre, Thompson Institute, University of the Sunshine Coast (UniSC), Birtinya, QLD, Australia., Dutton M; Thompson Brain and Mind Healthcare, PO Box 1544, Sunshine Plaza, QLD, 4558, Australia., Can AT; National PTSD Research Centre, Thompson Institute, University of the Sunshine Coast (UniSC), Birtinya, QLD, Australia., Lagopoulos J; Thompson Brain and Mind Healthcare, PO Box 1544, Sunshine Plaza, QLD, 4558, Australia., Kuballa AV; School of Health, UniSC, Sippy Downs, QLD, Australia; Centre for Bioinnovation, UniSC, Sippy Downs, QLD, Australia; Sunshine Coast Health Institute, Sunshine Coast Hospital and Health Service, Birtinya, QLD, 4575, Australia.
Source:
Journal of affective disorders [J Affect Disord] 2026 Feb 15; Vol. 395 (Pt B), pp. 120791. Date of Electronic Publication: 2025 Nov 30.
Publication Type:
Journal Article
Language:
English
Journal Info:
Publisher: Elsevier/North-Holland Biomedical Press Country of Publication: Netherlands NLM ID: 7906073 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1573-2517 (Electronic) Linking ISSN: 01650327 NLM ISO Abbreviation: J Affect Disord Subsets: MEDLINE
Imprint Name(s):
Original Publication: Amsterdam, Elsevier/North-Holland Biomedical Press.
MeSH Terms:
Ketamine*/administration & dosage , Ketamine*/pharmacology , Ketamine*/therapeutic use , Stress Disorders, Post-Traumatic*/drug therapy , Stress Disorders, Post-Traumatic*/immunology , Stress Disorders, Post-Traumatic*/genetics , Transcriptome*/drug effects , Inflammation*/genetics , Inflammation*/immunology , Inflammation*/drug therapy, Humans ; Male ; Female ; Adult ; Leukocytes, Mononuclear/drug effects ; Leukocytes, Mononuclear/immunology ; Administration, Oral ; Middle Aged ; Gene Expression Profiling ; Cytokines/genetics
Contributed Indexing:
Keywords: Gene expression; Immune response; Inflammation; Ketamine; PTSD; Transcriptome
Substance Nomenclature:
690G0D6V8H (Ketamine)
0 (Cytokines)
Entry Date(s):
Date Created: 20251202 Date Completed: 20251211 Latest Revision: 20251211
Update Code:
20260130
DOI:
10.1016/j.jad.2025.120791
PMID:
41330512
Database:
MEDLINE

Weitere Informationen

Ketamine provides rapid acting symptom relief, making it a promising intervention for post-traumatic stress disorder (PTSD). However, the mechanisms driving its long-term efficacy over weeks and months remain poorly understood. This study investigated the short- and sustained impacts on gene expression of an open-label six-week subanesthetic oral ketamine trial in 23 PTSD participants (9 males, 14 females). Peripheral blood mononuclear cells (PBMCs) were collected at baseline, one week (short-term), and four weeks (sustained) post ketamine treatment for RNA sequencing and transcriptome analysis. Differential expression analysis identified substantial and persistent transcriptomic changes over time, with 533 genes upregulated and 621 downregulated across timepoints. Notably, there was a 37% increase in differential gene expression between the short- and sustained responses, accompanied by a 6.5-fold rise in expression magnitude and an 8.8-fold enhancement in pathway activity. Pathway analysis emphasised important immune and inflammatory pathways that appear to be modulated by ketamine, including interferon alpha/beta signalling (z = 4), IL-17 signalling pathway (z = 3.36), and cytokine storm signalling (z = 4.26) and neutrophil degranulation (z = 6.0) which differed across timepoints. The findings suggest a transition from short-term inflammation suppression to sustained immune regulation. Changes in key cytokines, chemokines, interferons and antimicrobial peptides included, IL-6, IL-1β, IFI27, IL-10 signalling, CXCL8, SOCS1/3 and CAMP which represent central regulators of immune and inflammatory pathways. These molecular changes offer novel insights into the sustained therapeutic potential of ketamine for PTSD and highlight avenues for precision psychiatry and maintenance therapy to prevent relapse.
(Copyright © 2025 The Authors. Published by Elsevier B.V. All rights reserved.)

Declaration of competing interest There were no potential conflicts of interest identified throughout this review.