In a rat model of depression, modified electroconvulsive therapy (MECT) effectively reduced depressive symptoms but worsened cognitive impairments, increased hippocampal neuronal death, and triggered neuroinflammation. Adding esketamine, an FDA-approved antidepressant, reversed those cognitive deficits, reduced cell death and inflammation, and improved synaptic plasticity. Esketamine worked by increasing levels of the protein KLF4, which in turn blocked the p38 MAPK signaling pathway. When KLF4 was experimentally reduced, esketamine's protective effects disappeared, confirming its essential role. The findings suggest that combining esketamine with electroconvulsive therapy could protect against memory and thinking problems in patients.
This letter raises methodological concerns about a study claiming that low-dose S-ketamine during thoracic surgery reduces postoperative delirium and cognitive dysfunction in older adults. The authors point out that the study lacked details on how often delirium was monitored each day, relied solely on the Confusion Assessment Method for screening, did not report factors contributing to delirium in the ICU, and used a non-standard definition for cognitive impairment. They note inconsistencies with a recent randomized trial and argue these issues need clarification before accepting the conclusions.