Epigenetic aging and DNA methylation biomarker changes following ketamine treatment in patients with MDD and PTSD: a pilot study.
Level 4 - case-series / case-control
Uncontrolled single-arm pre-post pilot study (case series design).
PubMed 41173838 · doi:10.1038/s41398-025-03683-y
What was done
In a pilot clinical trial (NCT05294835), 20 individuals with major depressive disorder (MDD) or post-traumatic stress disorder (PTSD) received a course of six intravenous ketamine infusions at 0.5 mg/kg. Investigators evaluated baseline and post-treatment clinical symptom severity (PHQ-9 and PCL-5), DNA methylation profiles, immune cell composition, surrogate protein markers, and biological age using multiple epigenetic clocks (including OMICmAge, GrimAge V2, and PhenoAge).
What was found
The abstract reports decreases in depression (PHQ-9) and PTSD (PCL-5) symptom scores after the infusion series. Reductions were also observed in epigenetic biological age estimates measured by OMICmAge, GrimAge V2, and PhenoAge, alongside alterations in epigenetic biomarker proxies and surrogate protein markers. Specific numerical values, confidence intervals, and effect sizes were not provided in the abstract.
Why it matters
This pilot study suggests that the rapid antidepressant effects of ketamine may be accompanied by acute shifts in DNA methylation-based biological age metrics, offering a potential molecular readout for treatment response in trauma- and mood-related disorders.
Limits
The study is limited by a very small sample size (n = 20) and a single-arm, uncontrolled design, making it impossible to separate ketamine's pharmacological effects from placebo responses, regression to the mean, or normal intra-individual epigenetic fluctuation. The abstract does not provide numerical effect sizes, and long-term durability of the epigenetic changes was not assessed.
Cited by
- partial Psilocybin, ketamine, LSD, and ibogaine possess the strongest anti-aging properties among psychedelics, whereas heroin, methamphetamine, cocaine, and fentanyl accelerate aging.