This pilot study suggests six infusions may reduce several epigenetic aging measures in patients with MDD or PTSD while symptoms improve.
Evidence
A before-and-after pilot study of 20 participants with MDD or PTSD measured baseline and post-treatment DNA methylation, immune cell composition, and aging biomarkers and found decreases in PHQ-9 and PCL-5 scores alongside lower OMICmAge, GrimAge V2, and PhenoAge.
Caveat
The findings are preliminary because the sample was small and the abstract describes no control group, limiting causal inference about ketamine's effects on biological aging.
Simplified
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
33
Decrease in Score
Median difference in scores from baseline to post-treatment.
11
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.
Full Text
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Competing interests: KLD and SM are employed with Expedition Mental Health. AC, NCG, TLM, RMS, MSD, MPM, and VBD are employed with TruDiagnostic Inc. BCA is employed with Wild Health. ATH and RS have received consulting fees from TruDiagnostic Inc. for work unrelated to the present manuscript, and are named as inventors on a patent for the SystemsAge scores. Ethical approval: All study procedures were performed in accordance with relevant guidelines and regulations (including the Declaration of Helsinki and ICH-GCP). The protocol was reviewed and approved by the The Institutional Review Board of INSTITUTE OF REGENERATIVE AND CELLULAR MEDICINE gave ethical approval for this work (Protocol: Tru-012-2022v2; Approval/Registration: IRCM-2022-369). Informed consent was obtained from all participants prior to any study procedures. No animal experiments were performed. Consent for publication: This article does not include identifiable images or other personal data from human participants; therefore, consent for publication is not applicable.
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