JAK Signaling in Depression and Cognition in Male Football Players

Inclusion Criteria: * willing and able to give written informed consent * males * playing tackle football for at least 11 years * 30-55 years of age * Current Diagnostic and Statistical Manual (DSM)-V major depression or Bipolar, depressed type; or DSM-V major depression or Bipolar, depressed type in partial remission as diagnosed by the Structured Clinical Interview for the Diagnostic and Statistical Manual for Mental Disorders (SCID)-V * score of \>10 on the PHQ-9 from screening and HAM-D score ≥16 for study entry * off all antidepressant or other psychotropic therapy (e.g., mood stabilizers, antipsychotics, and sedative hypnotics) for at least 4 weeks before baseline visit (8 weeks for fluoxetine) or on a stable psychotropic regimen for at least 4 weeks (and no planned changes) * CRP ≥3 mg/L * PHQ-9 anhedonia (item #1) and cognitive (item #7) scores ≥2 Exclusion Criteria: * current or history of past autoimmune disorder * history or evidence (clinical or laboratory) of hepatitis B or C infection or human immunodeficiency virus infection * history of any type of cancer requiring treatment with more than minor surgery * unstable cardiovascular, endocrinologic, hematologic, hepatic, renal, or neurologic disease (as determined by physical examination, EKG, and laboratory testing) * significant hematological abnormalities at screening (ANC \< 1500, Hgb\<10, platelet\< 100,000) * history of progressive multifocal leukoencephalopathy * history of deep venous thrombosis * history of cardiovascular disease (coronary artery disease, congestive heart failure, stroke - controlled hypertension is OK) * major surgery within 6 months before screening, or will require major surgery during the study * current or recent (\<4 weeks before study start) viral (including COVID-19), bacterial, fungal, or parasitic infection, or any other active or recent infection * symptomatic herpes zoster infection at or within 12 weeks of study start * history of disseminated/complicated herpes zoster (for example, ophthalmic zoster or CNS involvement) * cirrhosis of the liver from any cause * Additional exclusion criteria apply