iScienceJan 21, 2026

DNA markers and clinical traits together may predict ketamine response in PTSD

Psychedelic Science Weekly Brief ↗PubMed ↗DOI ↗

Updated Jun 27, 2026

Abstract

Essence

Pretreatment blood DNA methylation patterns may help identify PTSD patients more likely to respond to ketamine.

Evidence

A machine-learning biomarker analysis used pretreatment blood DNA methylation profiles and clinical measures from the randomized CAP-ketamine PTSD trial to predict treatment response.

Caveat

The parent trial found no overall ketamine benefit over placebo, and the abstract does not report independent validation of the responder model.

Simplified

Post-traumatic stress disorder (PTSD) exhibits extensive clinical and biological variability, making treatment challenging. The Consortium to Alleviate PTSD (CAP)-ketamine trial, the largest randomized study of ketamine for PTSD, found no overall benefit of ketamine over placebo, underscoring the necessity to identify responsive subgroups. Using pre-treatment blood DNA methylation profiles and clinical measures from the CAP-ketamine trial, we applied machine learning to predict treatment response. A model based on 1,208 methylation sites achieved higher predictive accuracy than models using clinical variables alone, and combining both data types further improved performance. The methylation-derived score distinguished responders with 92.9% accuracy. The predictive CpGs were enriched near genes involved in glutamatergic signaling and immune regulation, as well as established PTSD risk loci. These findings suggest that peripheral DNA methylation patterns can identify individuals likely to benefit from ketamine, advancing precision approaches to PTSD pharmacotherapy.