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

Group 1 - Current major depressive episode (MDE) secondary to MDD Inclusion Criteria:

• good physical health with no active medical conditions

• non-cigarette smoking

• no past or current substance abuse or dependence

• negative urine pregnancy test at screening and scan days (for women)

• primary diagnosis of current major depressive episode (MDE) and major depressivedisorder (MDD) verified by SCID for DSM IV

• score greater than 19 on the 17 item HDRS

• non-response to a clinical trial of at least one antidepressant given at appropriateclinical dose

• willing to take medication for the duration of the trial and has previously takenantidepressants for the duration of the trial

• presently taking an antidepressant at a standard clinical dose.

Exclusion Criteria:

• history of neurological illness or autoimmune disorders

• never taken a tricyclic antidepressant or an antidepressant that raises norepinephrine

• received treatment with electroconvulsive therapy or mechanical brain stimulation inthe previous 6 months

• currently taking medication contraindicated or that may possibly interact with eitherminocycline or celecoxib

• known intolerance or allergy to minocycline, other tetracyclines, sulfonamides orNSAIDs

• taken diazepam or other benzodiazepine use within the past month, except for lorazepamand clonazepam

• use of anti-inflammatory drugs or tetracyclines lasting ≥1 week within the past month

• history of severe hepatic or renal insufficiency, asthma, allergies, gastrointestinaldisease, ischemic heart disease, cerebrovascular disease or congestive heart failure

• lactose intolerance Group 2 - Healthy Controls - Phase 1 (baseline scan) only Inclusion criteria:

• score below 8 on the 17 item HDRS

• good physical health

• non-cigarette smoking

• negative urine pregnancy test at screening and scan days (for women)

• negative urine screen for drugs of abuse Exclusion criteria:

• past or current diagnosis of axis I or axis II disorder as determined by the SCID Iand SCID II for DSM IV

• history of psychotropic medication use

• history of neurological illness or autoimmune disorder