Combining DNA methylation features and clinical characteristics predicts ketamine treatment response for PTSD
Year: 2025
Type: article
Abstract: 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.
Source: iScience
Authors: Amir Valizadeh, John D. Roache, Xinyu Zhang, Ying Hu, Ralitza Gueorguieva, Lynnette A. Averill, Mohini Ranganathan, Zuoheng Wang, Douglas E. Williamson, Paulo R. Shiroma, Matthew J. Girgenti, Ismene L. Petrakis, Argelio L. López-Roca, Stacey Young-McCaughan, Terence M. Keane, Alan L. Peterson, Chadi G. Abdallah, John H. Krystal, Ke Xu
Institutions: Yale University, VA Connecticut Healthcare System, South Texas Veterans Health Care System, The University of Texas at San Antonio, National Cancer Institute, Michael E. DeBakey VA Medical Center, Duke University, Durham VA Health Care System, Duke Medical Center, University of Minnesota, Minneapolis VA Health Care System, Minneapolis VA Medical Center, Brooke Army Medical Center, Joint Base San Antonio, Boston University, VA Boston Healthcare System, Baylor College of Medicine
Language: English
Subfield: Clinical Psychology
Field: Psychology
Domain: Social Sciences
Open Access status: gold
Estimated APC paid: $3,240
OpenAlex ID: W7115721752