medRxiv
May 27, 2025
Nathan J Wellington, Ana Paula Bouças, Paul Schwenn et al.
1 citation
preprint
People with post-traumatic stress disorder who had a sustained clinical response to oral ketamine showed distinct baseline differences in DNA methylation and gene expression across 112 genes compared with non-responders. Key biomarkers included DENND5B, ZFY, PDGFRA, CPT1A, AHRR, and others involved in metabolism, cell signaling, neuronal development, immune response, and synaptic plasticity. Non-responders had persistent dysregulation in these pathways, suggesting biological barriers to treatment. Clinically, sustained responders had more severe PTSD at baseline and responded at lower ketamine doses. The findings point toward molecular profiling that could help personalize ketamine therapy for PTSD.
medRxiv Preprint Server
November 26, 2024
Bonnie L. Quigley, Adem T. Can, Megan Dutton et al.
1 citation
preprint
A weekly low-dose oral ketamine treatment for six weeks significantly reduced PTSD symptoms in adults with PTSD, many of whom also had depression. PTSD Checklist scores dropped from an average of 40 before treatment to 17 after treatment, and remained reduced at 21 one month later. 73% of participants showed at least a 50% reduction in symptoms after treatment, and 59% maintained that improvement at follow-up. The results suggest oral ketamine is a feasible and tolerable treatment option, comparable to intravenous ketamine, and may overcome limitations of IV administration.
medRxiv Preprint Server
May 26, 2025
Nathan J. Wellington, Bonnie L. Quigley, Ana P. Bouças et al.
preprint
A six-week course of oral ketamine produced substantial and persistent changes in gene expression in 23 people with PTSD. Short-term effects included suppression of inflammation and antimicrobial activity; long-term effects shifted toward sustained immune regulation, inflammation remodulation, and tissue repair. Over four weeks, the number of genes whose activity changed rose by 37%, the magnitude of expression changes increased 6.5-fold, and pathway activity strengthened 8.8-fold. Key immune and inflammatory pathways modulated included interferon alpha/beta signaling, IL-17 signaling, cytokine storm signaling, neutrophil degranulation, and antimicrobial peptide signaling. Central regulators such as IL-6, IL-1β, IFI27, IL-10, CXCL8, SOCS1/3, and CAMP were implicated. These molecular changes point to mechanisms underlying ketamine's long-term therapeutic effects and suggest avenues for personalized maintenance therapy to prevent relapse.
medRxiv Preprint Server
March 2, 2025
Bonnie L. Quigley, Emerald Orr, Sophie Kafka et al.
preprint
In a 6-week open-label trial of low-dose oral ketamine for PTSD, blood samples from 25 participants showed a small but significant decrease in both BDNF and VEGF-A levels after treatment, with a positive correlation between the two biomarkers. This suggests ketamine's effects may involve a reciprocal interaction between BDNF and VEGF-A, offering potential insight into a biological mechanism for PTSD symptom reduction. Novel relationships between FKBP51, serotonin, and clinical scales were also observed. No significant changes in immune cytokines were detected, possibly because half the participants had low-grade inflammation and half did not.