Epigenetic aging and DNA methylation biomarker changes following ketamine treatment in patients with MDD and PTSD: a pilot study.
Kristin L Dawson, Athena May Jean M Carangan, Jessica Klunder, Natalia Carreras-Gallo, Raghav Sehgal, Samantha Megilligan, Benjamin C Askins, Nicole Perkins, Tavis L Mendez, Ryan M Smith, Matthew S Dawson, Michael P Mallin, Albert T Higgins-chen, Varun B Dwaraka
Translational psychiatry October 31, 2025 Peer reviewed DOI: 10.1038/s41398-025-03683-y via PubMed
Summary
In a study of 20 participants with major depressive disorder (MDD) or posttraumatic stress disorder (PTSD), six ketamine infusions led to decreased depression and PTSD scores, as measured by the PHQ-9 and PCL-5. Additionally, there was a reduction in epigenetic age according to several biomarkers, including OMICmAge, GrimAge V2, and PhenoAge. These findings suggest that ketamine treatment may influence biological aging in individuals with severe symptoms of depression or trauma.
Study at a glance
| Design | clinical trial |
|---|---|
| Sample size | 20 |
| Population | individuals with moderate to severe major depressive disorder or posttraumatic stress disorder |
| Key finding | Ketamine infusions resulted in decreased depression and PTSD scores and a reduction in epigenetic age among participants. |
Abstract
Major depressive disorder (MDD) and posttraumatic stress disorder (PTSD) are debilitating psychiatric conditions associated with poor health outcomes similarly observed in non-pathological aging. Ketamine 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 epigenetic age 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.