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.
Advances in experimental medicine and biology
January 1, 2026
Yunfei Tan, Kenji Hashimoto
1 citation
Treatment-resistant depression (TRD) affects about one-third of people with major depression, leading to higher suicide rates and impaired functioning. Originally defined as nonresponse to tricyclic antidepressants, TRD now includes inadequate response to multiple antidepressant classes, psychotherapy, and neuromodulation. Inconsistent criteria complicate prevalence estimates and diagnosis, with many presumed TRD cases actually involving bipolar depression or other disorders. Neurobiological research identifies glutamatergic dysregulation, default-mode network hyperactivity, impaired neuroplasticity, chronic inflammation, and epigenetic changes as markers. Clinically, patients experience persistent anhedonia, cognitive deficits, and sleep disturbances. Subtypes with distinct treatment responses have been identified, and biomarker-driven categories guide personalized care. Future work must standardize definitions and integrate multimodal biomarkers.
Translational psychiatry
November 24, 2025
Xin-Yu Li, Di Qiu, Ni Du et al.
1 citation
Patients with preexisting sleep disorders are at higher risk for postoperative sleep disturbance (PSD). In a randomized trial of 130 patients, intraoperative esketamine (0.3 mg/kg/h) reduced the incidence of PSD on postoperative day 1 (43.1% vs. 64.6%; odds ratio, 0.414) and lowered hydromorphone use. Preoperative oral microbiota profiles differed between patients who later developed PSD and those who did not, with specific bacterial taxa linked to sleep disturbance. The findings suggest esketamine may help prevent postoperative sleep disruption, possibly by modulating the oral microbiota.
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.
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.
Psychiatry and Clinical Psychopharmacology
March 30, 2026
Kenji Hashimoto, Feyza Arıcıoğlu, Mesut Çetin
Classical serotonergic psychedelics—psilocybin, DMT, 5-methoxy-DMT, and LSD—can produce rapid and sometimes durable improvements in mood under supervised conditions. The review synthesizes clinical evidence for these compounds in depression and related disorders, noting challenges such as small sample sizes, expectancy effects, and limitations in maintaining blinding. Mechanistic frameworks extend beyond 5-HT2A receptor activity, involving multiple serotonergic subtypes, glutamatergic modulation, synaptic plasticity, and brain network reorganization. Preclinical and clinical evidence points to neurotrophic mechanisms, particularly BDNF-TrkB signaling, as contributors to sustained effects. Acute mystical-type experiences may enhance response but are not strictly required, suggesting plasticity-promoting mechanisms can be partially dissociated from hallucinogenic effects. Peripheral contributions, including gut-brain axis interactions, may influence treatment durability.
Psychedelics.
October 14, 2025
Mingming Zhao, Jianjun Yang, Kenji Hashimoto
MDMA (ecstasy) is a unique entactogen that increases serotonin in the brain by reversing the serotonin transporter, and also affects catecholamine and oxytocin pathways. In clinical trials, MDMA-assisted psychotherapy has led to substantial improvements in treatment-resistant PTSD, though regulatory approval has been delayed due to concerns about unblinding and protocol rigor. Early placebo-controlled studies suggest benefits for autism spectrum disorder, eating disorders with comorbid PTSD, and anxiety from life-threatening illness. Large observational studies link MDMA use with lower depression rates, reduced suicidal ideation, and improved posttrauma coping, but causal inference is limited.