Methylome and transcriptome functional analysis identifies key biomarkers in ketamine’s sustained therapeutic effect on PTSD
medRxiv May 27, 2025 Nathan J Wellington, Ana Paula Bouças, Paul Schwenn et al. 1 citation preprint
People with post-traumatic stress disorder who had a sustained clinical response to oral ketamine showed distinct baseline differences in DNA methylation and gene expression across 112 genes compared with non-responders. Key biomarkers included DENND5B, ZFY, PDGFRA, CPT1A, AHRR, and others involved in metabolism, cell signaling, neuronal development, immune response, and synaptic plasticity. Non-responders had persistent dysregulation in these pathways, suggesting biological barriers to treatment. Clinically, sustained responders had more severe PTSD at baseline and responded at lower ketamine doses. The findings point toward molecular profiling that could help personalize ketamine therapy for PTSD.