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

Inclusion criteria

• MDD Patients:
• willing and able to give written informed consent
• men or women, 18-65 years of age
• primary diagnosis of DSM-V MDD, current, as diagnosed by the SCID-I
• score of ≥20 on the Beck Depression Inventory, which will include patients characterized as having "moderate/severe" (20-28) or "very-severe" (29-63) depressive symptoms
• off all antidepressant therapy for at least 8 weeks prior to the baseline visit
• Healthy Controls:
• willing and able to give written informed consent
• men or women, 18-65 years of age

Exclusion criteria

• MDD Patients:
• history of any bipolar disorder or psychotic disorder
• active psychotic symptoms of any type
• substance abuse/dependence within 6 months of study entry (as determined by SCID)
• unstable cardiovascular, endocrinologic, hematologic, hepatic, renal, or neurologic disease (as determined by physical examination and laboratory testing), including upper respiratory disease or asthma, glaucoma or porphyria.
• active suicidal ideation as determined by a score ≥3 on the Columbia Suicide Severity Rating Scale (C-SSR)
• use of any recreational drugs as confirmed by urine drug screen at the time of scanning
• pregnancy or lactation
• use of glucocorticoids at any time during the study
• Raynaud's disease that may interfere with the cold-pressor
• contraindications for MRI
• MMSE score \<28
• elevated blood pressure prior to infusion (systolic \> 160 or diastolic \>100)
• history of treatment resistance as determined by ATRQ
• prior adverse reaction to ketamine
• use of antipsychotic medications
• use of greater than 2mg daily of lorazepam or similar benzodiazipine.
• Regular smoker as self-reported
• Healthy Controls:
• evidence of any psychiatric disorder with exception of specific phobia, and no history of any psychiatric disorder except mild past substance use disorder as diagnosed by the SCID-I
• history of any substance abuse within the last 6 months
• use of any recreational drugs as confirmed by urine drug screen at the time of scanning
• pregnancy or lactation
• use of glucocorticoids at any time during the study
• Raynaud's disease that may interfere with the cold-pressor
• contraindications for MRI
• MMSE score \<28
• Regular smoker as self-reported