Biomarkers of Neuroinflammation and Anti-Inflammatory Treatments in Major Depressive Disorder

There will be three Phases in the study. Only MDE subjects will be invited to continue to Phase 2 and 3. Subjects will be invited to continue to the subsequent Phase given they meet entry criteria described below: Phase 1: The investigators will evaluate whether TSPO is elevated in individuals during a current MDE compared to healthy controls. Eligible participants will receive one \[18F\]FEPPA PET scan and one MRI scan. Other measures will include urine sample, blood samples for genetic and peripheral biomarker analysis, a neurocognitive battery, mood scales and questionnaires. Phase 2: Participants who have elevated TSPO VT in Phase 1 and are agreeable to receiving minocycline will be invited to participate in Phase 2. Based on our previous results participants will be considered candidates for Phase 2 if TSPO VT ≥ 10.5 (HAB) or ≥8.5 (MAB) in any of the primary regions of interest (prefrontal cortex, anterior cingulate cortex or insula). Eligible participants will be invited to participate in a randomized, double blind, placebo controlled trial, to receive either minocycline or placebo. After the eight weeks of treatment, participants will receive one \[18F\]FEPPA PET scan. Other measures will include urine samples, blood samples, mood scales and questionnaires. Phase 3: If, after the initial eight week treatment period with either minocycline or placebo, any participant continues to have depressive symptoms (17-item Hamilton Depression Rating Scale score ≥ 8) they will be invited to participate in an eight week open label trial of celecoxib. Participants not eligible for Phase 2 may also be invited to participate in Phase 3 directly from Phase 1.