Molecular profiling of Ketamine's rapid antidepressant effect

One third of the patients with major depressive disorder suffer from treatment resistance and do not respond to commonly used antidepressants. Ketamine, a drug that works through a different mechanism, improves depressive symptoms within hours and is particularly effective in treatment-resistant patients. Scientists at the Max Planck Institute of Psychiatry in Munich have for the first time identified metabolite alterations, affected pathways and biomarker candidates for the Ketamine treatment response in mice. An improved understanding of the molecular events causing the rapid antidepressant effect of Ketamine will allow the development of alternative drugs with a similar mode of action but fewer side effects.

Ketamine, a drug that has been applied as an anesthetic for many years, has recently been shown to have rapid antidepressant activities. The drug is used to treat patients resistant to conventional antidepressants. Unlike other antidepressants, Ketamine improves depressive symptoms already within a few hours, but hallucinogenic side effects in some patients have so far prevented Ketamine's routine use as a first-line drug.

Scientists around Christoph Turck, Research Group Leader at the Max Planck Institute of Psychiatry in Munich, in collaboration with Marianne Müller-Sitz at the University of Mainz, investigated the effects of Ketamine in the hippocampus of mice, a brain region associated with depression. Patients suffering from depression often show impairments in their memory, which is highly dependent on the hippocampus. Further, a dysregulated connectivity network of several brain regions including the hippocampus was observed in these patients.

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