Glutamatergic Adaptation to Stress as a Mechanism for Anhedonia and Treatment Response With Ketamine

This study looks at how ketamine affects people with Major Depressive Disorder (**MDD**) in areas like decision-making and feelings. Ketamine is often used for anesthesia, but in this study, small doses are used to see if it can help with depression symptoms. The study uses questionnaires (written questions), neuroimaging (pictures of the brain), and behavioral tasks (activities) to measure the effects. Two groups are involved: one with MDD patients receiving ketamine or a fake treatment (placebo) and another with healthy people who don’t get any treatment, only doing the tasks and brain imaging. The research checks how a brain chemical, glutamate, reacts to stress in both groups.

• The study lasts several weeks, and participants must be off antidepressants for 8 weeks before starting.
• Participants with MDD will be checked with brain scans and tests before and after ketamine treatment.
• Risks include possible reactions to ketamine; healthy volunteers will not undergo treatment.