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

This study is investigating how the brain chemical glutamate responds to stress, and whether this response is linked to loss of pleasure (anhedonia) and how well ketamine works as a treatment for severe depression. **You may be eligible if...** - You are 18–65 years old - You have been diagnosed with moderate to severe major depression (MDD) and are not currently taking antidepressants (must be off for at least 8 weeks) - Healthy volunteers without psychiatric conditions are also welcome **You may NOT be eligible if...** - You have a history of bipolar disorder, psychosis, or schizophrenia - You have a substance use disorder within the last 6 months - You have active suicidal thoughts - You have had a bad reaction to ketamine before - You are pregnant or breastfeeding - You smoke regularly or use recreational drugs - You have certain medical conditions such as uncontrolled high blood pressure or MRI contraindications Talk to your doctor to see if this trial is right for you.