Epigenetic aging and DNA methylation biomarker changes following ketamine treatment in patients with MDD and PTSD: a pilot study

Nov 1, 2025Translational psychiatry

Changes in biological aging and DNA markers after ketamine treatment in patients with depression and PTSD

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Abstract

A reduction in was observed in 20 participants following a course of six infusions for moderate to severe depression or PTSD.

Depression and PTSD symptoms decreased in participants after ketamine treatments, as measured by the PHQ-9 and PCL-5.
Significant changes were noted in various epigenetic biomarkers, specifically OMICmAge, GrimAge V2, and PhenoAge, after treatment.
The study indicates that ketamine may influence biological aging processes in individuals with MDD and PTSD.
Findings support existing literature on ketamine's effects on biomarkers related to mental health and biological aging.

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Major depressive disorder (MDD) and posttraumatic stress disorder (PTSD) are debilitating psychiatric conditions associated with poor health outcomes similarly observed in non-pathological aging. is a dissociative anesthetic and NMDA receptor antagonist with demonstrated rapid reduction in symptoms associated with Treatment Resistant Depression (TRD) and PTSD. Ketamine's effects on biological aging have not been extensively studied among patients with moderate to severe symptoms of depression and/or trauma. To address this gap, this study looked at the changes in non-epigenetic measures, DNA methylation levels, immune cell composition, and biological age based on various epigenetic biomarkers of aging, of 20 participants at baseline and after completion of a course of six ketamine 0.5 mg/kg infusions in individuals with MDD or PTSD. As expected, depression and PTSD scores decreased in participants following ketamine infusion treatments as measured by the PHQ-9 and PCL-5. We observed a reduction in in the OMICmAge, GrimAge V2, and PhenoAge biomarkers. In order to better understand the changes in epigenetic age, we also looked at the underlying levels of various Epigenetic Biomarker Proxies (EBPs) and surrogate protein markers and found significant changes following ketamine treatment. The results are consistent with existing literature on ketamine's effects on different biomarkers. These results underline the ability of GrimAge V2, PhenoAge, and OMICmAge in particular, to capture signals associated with key clinical biomarkers, and add to the growing body of literature on ketamine's epigenetic mechanisms and their effect on biological aging. Clinical Trial Code. NCT05294835.

Key numbers

Decrease in Score

Median difference in scores from baseline to post-treatment.

Decrease in Score

Median difference in scores from baseline to post-treatment.

0.038

Reduction in CD4T Memory Cells

Unadjusted p-value indicating significance of change post-treatment.

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Ketamine might be reversing biological aging while treating depression

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Epigenetic aging and DNA methylation biomarker changes following ketamine treatment in patients with MDD and PTSD: a pilot study

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