Blood biomarker changes and relationships after low dose oral ketamine treatment for post-traumatic stress disorder (PTSD)
medRxiv Preprint Server – March 02, 2025
Source: medRxiv
Summary
Though ketamine shows promise for PTSD, its biological impact has been largely unknown. Recent research explored how low-dose oral ketamine affects blood biomarkers in 25 individuals with PTSD over six weeks. A key finding revealed a novel interaction between brain-related biomarkers, BDNF and VEGF-A, which decreased after treatment. This suggests a potential biological mechanism for the observed PTSD symptom reduction. Additionally, new links were found between FKBP51 and serotonin levels and clinical improvements. This pioneering work offers important insights into how ketamine treatment may work at a biological level.
Abstract
Ketamine has been investigated as a treatment alternative for PTSD for the last 20 years, yet there have been virtually no reports of biological changes or biomarker characterisation related to treatment. To address this significant gap, this study analysed blood samples from 25 participants with PTSD who took part in an open-label 6-week trial of low dose oral ketamine treatment. Serum and plasma samples were quantified before and after ketamine treatment for brain-derived neurotrophic factor (BDNF), vascular endothelial growth factor A (VEGF-A), serotonin, FK506 binding protein 51 (FKBP51) and a panel of cytokines (interleukin (IL)-1β, IL-2, IL-4, IL-6, IL-12p70, IL-17A and tumour necrosis factor alpha (TNFα)). Analysis of BDNF and VEGF-A levels detected a significant positive correlation between the two biomarkers and a small but statistically significant decrease in both measures after ketamine treatment. This novel finding reinforces evidence that ketamine’s effects may rely on a reciprocal interaction between BDNF and VEGF-A, offering potential insights into a biological mechanism underpinning PTSD symptom reduction. Additionally, the analysis of FKBP51 and serotonin revealed novel relationships between these biomarkers and clinical scales, before and after ketamine treatment. Finally, significant changes or relationships involving the immune cytokines were not detected, possibly because half the participants presented with low-grade inflammation while the other half did not. This study represents the first comprehensive analysis of blood biomarkers before and after ketamine treatment for PTSD and reveals important biological changes and relationships related to this treatment.