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Published VersionCC BY V4.0, Open Access
Journal article
Temporal immune effects of Oral ketamine on PTSD: Transcriptomic evidence of short-term inflammation suppression and sustained immune Remodelling
Journal of Affective Disorders, Vol.395(Pt B), pp.1-11
2026
PMID: 41330512
Appears in Thompson Institute Research Collection
Abstract
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.
Details
- Title
- Temporal immune effects of Oral ketamine on PTSD: Transcriptomic evidence of short-term inflammation suppression and sustained immune Remodelling
- Authors
- Nathan J. Wellington (Corresponding Author) - University of the Sunshine Coast, Queensland, Thompson InstituteBonnie L. Quigley - University of the Sunshine Coast, Queensland, Thompson InstituteAna P. Bouças - University of the Sunshine Coast, Queensland, Thompson InstituteMegan Dutton - Thompson Brain and Mind Healthcare (Australia)Adem T. Can - University of the Sunshine Coast, Queensland, Thompson InstituteJim Lagopoulos - Thompson Brain and Mind Healthcare (Australia)Anna V. Kuballa - University of the Sunshine Coast, Queensland, School of Health - Biomedicine
- Publication details
- Journal of Affective Disorders, Vol.395(Pt B), pp.1-11
- Publisher
- Elsevier BV
- Date published
- 2026
- DOI
- 10.1016/j.jad.2025.120791
- ISSN
- 1573-2517; 0165-0327
- PMID
- 41330512
- Copyright note
- © 2025 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
- Data Availability
- Illumina RNA-Seq 20 million sequence paired end reads, raw and processed data alongside deidentified metadata has been registered with the Gene Expression Omnibus (GSE288174) and support the findings of this study. Deidentified behavioural scale results are available on request although original copies are protected for participant privacy.
- Grant note
- The Oral Ketamine Trial on Post-Traumatic Stress Disorder was funded internally through the Thompson Institute.
- Organisation Unit
- School of Health - Biomedicine; Thompson Institute; Centre for Bioinnovation
- Language
- English
- Record Identifier
- 991192145002621
- Output Type
- Journal article
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