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