Ketamine treatment effects on DNA methylation and Epigenetic Biomarkers of aging
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 Smith, Matthew S Dawson, Michael P Mallin, Albert T. Higgins-Chen, Varun B. Dwaraka
medRxiv Preprint Server September 10, 2024 preprint DOI: 10.1101/2024.09.10.24313258 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Observational cohort |
|---|---|
| Sample size | 20 |
| Population | Individuals with major depressive disorder or posttraumatic stress disorder |
| Intervention | Ketamine infusions |
| Dose | 0.5 mg/kg |
| Duration | 2-3 week treatment course |
| Topics | Depression Ketamine PTSD Esketamine |
| Keywords | Ketamine infusions Mental health Psychiatric conditions Psychiatric distress Accelerated biological aging Aging process Cellular level Epigenetics Epigenetic biomarkers |
| Citations | 4 |
| Key findings | Ketamine infusions reduced epigenetic age as measured by OMICmAge, GrimAge V2, and PhenoAge biomarkers in individuals with MDD or PTSD. |
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 2-3 week treatment course of 0.5 mg/kg ketamine 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.
Comparable studies
Other observational and cohort studies on ketamine for PTSD, most cited first.
Citations in the library
Cited by 4
- The Effects of Psychotherapy on Single and Repeated Ketamine Infusion(s) Therapy for Treatment-Resistant Depression: The Convergence of Molecular and Psychological Treatment. International Journal of Molecular Sciences July 11, 2025
- Cortical Mechanisms Contributing to Ketamine-Induced Dissociation The Neuroscientist December 26, 2025
- Psilocybin reduces depressive-like behavior and improves cognition in healthy aging mice via epigenetic regulation of plasticity- and immune-related genes Research Square November 5, 2025
- Brain-epigenome wide association study (BEWAS) on the effects of two emerging psychedelics: ketamine & MDMA bioRxiv Preprint Server July 3, 2025
Cites 15
- Efficacy and Safety of Flexibly Dosed Esketamine Nasal Spray Combined With a Newly Initiated Oral Antidepressant in Treatment-Resistant Depression: A Randomized Double-Blind Active-Controlled Study American Journal of Psychiatry May 21, 2019
- Efficacy and Safety of Intranasal Esketamine Adjunctive to Oral Antidepressant Therapy in Treatment-Resistant Depression JAMA Psychiatry December 27, 2017
- Efficacy and Safety of Intranasal Esketamine for the Rapid Reduction of Symptoms of Depression and Suicidality in Patients at Imminent Risk for Suicide: Results of a Double-Blind, Randomized, Placebo-Controlled Study American Journal of Psychiatry April 16, 2018
- Efficacy of Intravenous Ketamine for Treatment of Chronic Posttraumatic Stress Disorder JAMA Psychiatry April 16, 2014
- A Double-Blind, Randomized, Placebo-Controlled, Dose-Frequency Study of Intravenous Ketamine in Patients With Treatment-Resistant Depression American Journal of Psychiatry April 8, 2016
and 10 more in the library