Ketamine, a drug that blocks NMDA glutamate receptors, produces symptoms resembling schizophrenia. Analyzing the Positive and Negative Syndrome Scale (PANSS) in four groups—135 healthy people given ketamine or saline, 187 chronic ketamine abusers, 154 early-course schizophrenia patients, and 522 chronic schizophrenia patients—revealed five similar symptom dimensions (positive, negative, cognitive, depressed, excitement/dissociation) across all groups. The chronic ketamine group's symptom structure more closely matched the schizophrenia groups than the acute ketamine group did. Symptoms were milder in ketamine users than in schizophrenia patients (Cohen's d = 0.7). The findings suggest ketamine-induced psychosis shares symptom dimensions with schizophrenia, though confounding factors warrant caution.
Post-traumatic stress disorder varies greatly in its clinical and biological features, making treatment difficult. The largest randomized trial of ketamine for PTSD found no overall benefit over placebo, highlighting the need to identify which patients might respond. Using pre-treatment blood DNA methylation profiles and clinical data from that trial, machine learning models predicted treatment response. A model based on 1,208 methylation sites outperformed models using only clinical variables, and combining both data types improved accuracy further. The methylation-derived score identified responders with 92.9% accuracy. Predictive methylation sites were near genes involved in glutamatergic signaling, immune regulation, and known PTSD risk loci, suggesting peripheral DNA methylation patterns can guide precision pharmacotherapy for PTSD.