Presynaptic Imaging in Major Depressive Episodes After COVID-19

Participants will undergo two positron emission tomography (PET) scans, one [11C]DTBZ scan (for vesicular monoamine transporter 2 (VMAT2) and one [18F]SDM8 scan (for synaptic vesicle glycoprotein 2A (SV2A)), as well as one magnetic resonance imaging (MRI) scan.

The main question[s] it aims to answer are:

• The investigators will determine if VMAT2 binding potential (VMAT2 BPND) is reduced in ventral striatum and dorsal putamen in COVID-DNP.
• The investigators will determine if SV2A total distribution volume (SV2A VT) is reduced in ventral striatum and dorsal putamen in COVID-DNP

Inclusion criteria

• New onset MDE within 3 months after mild or moderate COVID-19, with MDE verified by the research version SCID for DSM 5. See "Positive COVID-19 diagnosis" listed after inclusion/exclusion criteria for a description of how this is determined.
• Age 18 to 75.
• Good general physical health with no active medical conditions based on self-report (except migraine or PASC).

Exclusion criteria

• Use of antidepressants in the previous month (6 weeks for fluoxetine).
• Use of stimulant medication affecting dopamine release in the previous month
• Use of antipsychotics in the previous month
• History of neurological disease (except migraine, and PASC) based on self-report
• Use of medications or herbal products or natural health products with central nervous system effects in past 2 weeks based on self-report
• Presence of cigarette smoking in the past two months, based on self-report
• Lifetime diagnosis of severe Substance or Alcohol Use Disorder, or diagnosis of mild to moderate Substance or Alcohol Use Disorder in the past two years, based on self-report and verified by the Research Version of Structured Clinical Interview for Diagnostic and Statistical Manual-5 (SCID-5-RV)
• Use of recreational drugs, including marijuana, in the past two months, based on self-report and verified by the Research Version of Structured Clinical Interview for Diagnostic and Statistical Manual-5 (SCID-5-RV)
• Positive urine drug or cotinine screen at any timepoint during the study
• History of psychotic symptoms secondary to schizophrenia, schizophreniform, bipolar disorder, or brief psychotic disorder prior to COVID-19, based on self-report and verified by the Research Version of Structured Clinical Interview for Diagnostic and Statistical Manual-5 (SCID-5-RV)
• Currently pregnant, based on self-report or positive pregnancy test at any timepoint during the study, in females (in our PET Centre females up to 65 years of age are given a urine pregnancy test prior to every PET scan)
• Breastfeeding (for females)
• Current disorders of coagulation, blood or ongoing use of anticoagulant medication, based on self-report
• Claustrophobia, based on self-report
• Weight over 400lbs and height over 7ft (requirements for fitting in the scanners and hospital gowns)
• Presence of metal implant, object or electrical devices that are contraindicated for MRI, based on self-report
• Severe allergic reaction to alcohol