High-dose S-ketamine (0.5 mg/kg) significantly reduced pain and depression scores one and three days after surgery in cervical carcinoma patients with mild to moderate depression, compared to low-dose S-ketamine, racemic ketamine, or a control. The high-dose group also showed higher serum levels of BDNF and 5-HT at those time points. However, no differences between groups remained one week after surgery. Low-dose S-ketamine (0.25 mg/kg) and racemic ketamine did not produce significant improvements. The findings suggest that subanesthetic S-ketamine offers short-term benefits for postoperative depression and pain in this population, with the higher dose being more effective than racemic ketamine.
Adding a low dose of the anesthetic esketamine to a multimodal pain regimen improved the quality of recovery for patients after thoracoscopic lung surgery, while two different regional nerve blocks—erector spinae plane block and intercostal nerve block—provided similar benefits. In a randomized trial of 100 adults, those receiving intravenous esketamine (0.3 mg/kg) scored an average of 111.5 on the quality-of-recovery scale at 24 hours, compared with 105.4 for placebo, a difference exceeding the minimal clinically important threshold of 6.0 points. The esketamine group also had higher scores at 48 hours and hospital discharge. No significant interaction occurred between esketamine and the type of nerve block, and the two blocks yielded comparable recovery scores, suggesting they can be used interchangeably.
In a mouse model of depression induced by chronic social defeat stress, susceptible mice showed reduced social interaction, lower sucrose preference, decreased NRG1 protein expression in the prefrontal cortex, and increased immobility time compared to controls. A subanesthetic dose of esketamine increased NRG1 expression in the prefrontal cortex within 30 minutes and improved social interaction and reduced immobility at both 30 minutes and 24 hours post-injection. No significant changes were observed in GAD67 or ErbB4 expression. Esketamine may rapidly improve depressive-like behavior by regulating the NRG1-ErbB4 signaling pathway.
Effective connectivity within the default mode network (DMN) is associated with specific genetic variants in Alzheimer's disease and mild cognitive impairment. Analyzing longitudinal resting-state fMRI and genetic data from 111 subjects (319 scans) from the ADNI database, researchers fitted dynamic causal models to estimate brain connectivity in 4-region and 6-region networks. They related connectivity to single nucleotide polymorphisms (SNPs) using both linear mixed effect models and function-on-scalar regression, with parametric bootstrap approaches for testing. The study reports exploratory patterns of SNP-connectivity associations that show stability across the two statistical methods, suggesting genetic influences on DMN connectivity in these conditions.