Pilot Study: Establishing Glutamatergic Changes in Rapid Antidepressant Effects of Ketamine

Consent and Virtual Screening: Participants who meet initial inclusion criteria via phone screen will be invited to the complete a virtual visit that will include additional screening (e.g. Medical history), Structured Clinical Interview for DSMV (SCID) and clinician-administered measures of mood to determine final study eligibility. At the outset of this visit, all participants will receive verbal and written explanation of the general goals and risks of the study and will virtually sign an informed consent. The results of the SCID will be used to characterize the study population and to determine whether they meet criteria for any diagnoses that would preclude participation (e.g. psychotic disorders). Their medical history will be reviewed by a study staff member to ensure that patients are diagnostically eligible. At-home Sleep Recording: Following enrollment participants will complete a 7-day at-home sleep diary to assess sleep patterns prior to ketamine infusion. Sleep diaries will be completed either online via REDCap or with paper forms, based on participant preference and internet access. In-laboratory Ketamine Infusion Protocol: On the study day, participants will arrive at the Hospital of the University of Pennsylvania at 9:00 AM. After initial orientation, they will undergo a baseline MRI scan between 9:00 AM and 11:00 AM. The MRI will utilize a 7T Siemens Terra system for high-resolution GluCEST imaging to capture glutamatergic activity. Following the scan, participants will complete baseline mood assessments, including the HAM-D, PANAS, VAS, and POMS scales. A light snack will be provided before the ketamine infusion begins between 12:00 PM and 1:00 PM. Participants will receive a 40-minute infusion of ketamine (0.5 mg/kg) under the supervision of a registered nurse and anesthesiologist. Continuous monitoring of vital signs (blood pressure, heart rate, oxygen levels) will be performed throughout the infusion. If adverse symptoms arise, the infusion may be paused or stopped at the discretion of the study physician. Following the infusion, participants will be observed for 1 hour to ensure stable vitals and recovery. Mood assessments will be repeated after the infusion to measure changes in emotional state. A second MRI scan will be conducted between 4:00 PM and 6:00 PM to assess changes in glutamatergic activity post-infusion. After completing the scan and final assessments, participants will be discharged.