Translational Psychiatry
May 20, 2026
Xin Ding, Rumi Murayama, Yi Cai et al.
1 citation
The drug combination KarXT (xanomeline plus trospium) reverses cognitive deficits caused by phencyclidine (PCP) in adult male mice, and this effect is linked to changes in gut and lung microbiota. PCP disrupted recognition memory and caused region-specific imbalances in microbes, especially in the small intestine and cecum. KarXT restored memory and normalized several bacterial species elevated by PCP, including Bacteroides fragilis and Veillonella ratti. Restoration of certain lung and gut microbes correlated with improved memory. The findings suggest that KarXT's cognitive benefits involve microbial modulation, which may guide efforts to reduce gastrointestinal side effects in muscarinic therapies for schizophrenia.
Progress in neuro-psychopharmacology & biological psychiatry
June 20, 2026
Xin Ding, Kenji Hashimoto, Jian-Jun Yang
Xanomeline and ketamine, two mechanistically distinct antidepressants, partially converge on common molecular pathways despite acting through different upstream receptors. Network pharmacology and molecular docking identified 368 overlapping targets for xanomeline with major depressive disorder and 714 for ketamine. Three shared signaling pathways emerged: EGFR tyrosine kinase inhibitor resistance, Ras signaling, and Rap1 signaling. Three core proteins—EGFR, IGF1R, and SRC—were common to both drugs. Xanomeline associated more strongly with receptor tyrosine kinase and PI3K/AKT signaling, while ketamine linked more to synaptic transmission, NMDA receptors, and glutamatergic signaling. These hypothesis-generating findings suggest partial convergence on downstream plasticity-related signaling nodes.
Clinical psychopharmacology and neuroscience : the official scientific journal of the Korean College of Neuropsychopharmacology
May 31, 2026
Yong Yue, Yi Cai, Rumi Murayama et al.
Gut bacteria contribute to baseline central oxytocin signaling in rats, but are not necessary for the acute oxytocin release triggered by MDMA. Male rats given broad-spectrum antibiotics for seven days showed enlarged ceca, confirming microbiome disruption, yet maintained stable body weight. Baseline oxytocin expression in the paraventricular and supraoptic nuclei of the hypothalamus was significantly reduced after antibiotic treatment, while peripheral oxytocin levels remained unchanged. MDMA administration increased central oxytocin expression similarly in both antibiotic-treated and control rats, and MDMA-induced peripheral oxytocin levels also did not differ between groups. The findings indicate that gut microbiota help maintain central oxytocin under normal conditions but are not required for MDMA's oxytocin-activating effects.