iScience
January 16, 2026
Amir Valizadeh, John D Roache, Xinyu Zhang et al.
2 citations
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.
Molecular psychiatry
April 13, 2026
Xin Zhao, Xinyu Zhang, Shiying Yuan et al.
Ketamine, a drug used for anesthesia and rapid antidepressant effects, also modulates systemic immunity and protects organs through interactions with the gut microbiota, microbial metabolites, and immune-cell trafficking. Along the gut-brain axis, ketamine restores microbial balance, normalizes short-chain fatty acid levels, and reduces migration of gut-derived immune cells to the central nervous system, correlating with reduced neuroinflammation and depressive-like behaviors. Through the gut-lung axis, ketamine limits bacterial translocation and reduces pulmonary infiltration of pro-inflammatory cells, suggesting potential relevance in acute lung injury. Arketamine appears to provide more sustained neuroprotection with fewer adverse effects than esketamine. The findings suggest broad therapeutic potential for neuropsychiatric and inflammatory diseases, but causal studies are needed.
Journal of neuroinflammation
December 18, 2025
Mengqi Han, Bing Xie, Yuan Yu et al.
Chronic stress triggers depression by activating a gut-immune-brain pathway. In mice exposed to chronic restraint stress, gut microbiota changes caused small intestinal γδ T cells to migrate to the brain, where they released interleukin-17A (IL-17A). This IL-17A impaired a mitochondrial cleanup process called mitophagy in the hippocampus, leading to reduced energy production, damaged synapses, and depression-like behavior. Blocking γδ T cell migration, removing a key receptor on these cells, or giving the antidepressant arketamine all restored mitophagy and improved behavior. The findings identify a specific chain from gut microbes to immune cells to brain mitochondria that drives stress-induced depression, and point to arketamine as a potential treatment targeting this pathway.