Pilot Study: Establishing Glutamatergic Changes in Rapid Antidepressant Effects of Sleep Deprivation

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. This visit will be conducted virtually to limit the number of in-person study visits. 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 For 7 days prior to the in-lab study visit, participants will be asked to keep an at-home sleep schedule, consistent with their habitual sleep/wake schedule (e.g., 10:30 PM 6:00 AM). Participants will also consent to refraining from napping, using alcohol and drugs, and limiting caffeine use to one caffeinated beverage before noon on the day of study. These procedures will be confirmed using sleep diary. Sleep diaries will be completed via the REDCap web-based application if participants feel comfortable with an internet-based platform and have consistent Internet access. Paper and pencil versions of sleep diaries will also be available. Study staff will compare across these methods to verify adherence to study guidelines prior to the in-lab study. In-laboratory Study Protocol Throughout in-laboratory period, participants will be continuously behaviorally monitored by trained staff in a semi-isolated living area, and have contact with only nurses and research. No caffeinated products will be allowed. When not being tested during the study, participants will be permitted to watch television, converse with the study monitors or play games. Physical activity will be kept to a minimum to avoid any effect of exercise on circadian rhythms or sleep. They will not be allowed to leave the study venue. Day 1 (D1) Participants will arrive at the Clinical Research Center for Sleep (CRCS) in the afternoon of their scheduled overnight, at no later than 1700h. Following their arrival and orientation, participants are accompanied to the MRI for the neuroimaging protocol to acquire data on rested baseline brain activity before sleep deprivation. Following the neuroimaging protocol, participants will return to CRCS and complete mood assessments (HAM-D, PANAS, VAS, POMS). Night 1 (N1; Sleep deprivation). Sleep will not be permitted from the end of D1 until 1400h on D2 (approximately 30 hours). Day 2 (D2) Following breakfast at approximately 0700h, all participants will again complete mood assessments. Participants will complete the neuroimaging protocol again between 0900-1200h. Following the neuroimaging protocol, participants will be discharged or allowed to remain in the CRCS for recovery sleep.