Stress and Inflammation in Late-Life Depression

Inclusion Criteria

• Age 18-80, male or female, any race;
• Absence of clinical dementia
• English speaking
• Blood pressure not exceeding 150/90 mmHg, treated or untreated
• Weight greater than 110 lbs
• Normal result on liver-function test
• No history of ulcer disease or GI bleeding
• No renal insufficiency

Additional Inclusion Criteria for Depressed Participants:

• DSM-IV criteria for Major Depressive Disorder
• HAM-D greater than 18

Exclusion Criteria

• Known history of relevant severe drug allergy or hypersensitivity (e.g. to Citalopram or Escitalopram, and/or to celecoxib, aspirin, or other NSAIDs only for Phase 2; known demonstration of allergic-type reactions to sulfonamides);
• Does not speak English;
• Cannot give informed consent;
• MRI contraindications (e.g., foreign metallic implants, pacemaker);
• Known primary neurological disorders, such as Parkinson's disease, Alzheimer's disease, traumatic brain injury, cognitive impairment or dementia,
• Known severe inflammatory disease such as systemic lupus erythematosis, known autoimmune diseases, such as multiple sclerosis, rheumatoid arthritis; Screen + for RF, ANA, HIV, Hepatitis B or C.
• Clinical Dementia Rating Scale score greater than 0;
• Diagnosis of a chronic psychiatric illness other than MDD at the discretion of the study doctor;
• Significant handicaps (e.g. uncorrected hearing or visual impairment, mental retardation) that would interfere with testing;
• Bleeding diathesis;
• Severe Medical problem, which in the opinion of the investigator would pose a safety risk to the subject;
• Clinically significant cardiovascular disease that will be assessed on a case-by-case basis. Clinically significant cardiovascular disease usually includes one or more of the following: cardiac surgery or myocardial infarction within the last 4 weeks; unstable angina; acute decompensated congestive heart failure or class IV heart failure; current significant cardiac arrhythmia or conduction disturbance, particularly those resulting in ventricular fibrillation, or causing syncope or near syncope; uncontrolled high blood pressure; QTc greater than 450msec (by history for subjects with cardiac disease); documented prior stroke;
• Clinically significant abnormalities on EKG. Primary AV block or Right bundle branch block are not necessarily exclusionary;
• Current diagnosis of cancer
• Current diagnosis of HIV, active Hepatitis B and/or Hepatitis C
• Use of an Investigational medicine within the past 30 days;
• Use of Coumadin, Warfarin within the past 2 months;
• Current treatment with psychotropic drugs or drugs that affect the CNS such as beta-blockers, mood stabilizers, antipsychotics, steroids or non-steroidal anti-inflammatory medications or other antidepressants. No subjects will be included in the study unless they have been off all psychotropics for at least 3 weeks, except in the case of fluoxetine, where 5 weeks off treatment will be required;
• Current alcohol or substance abuse disorder, schizophrenia or other psychotic disorder, bipolar disorder, or current OCD;
• Abnormal liver-function test
• History of ulcer disease, Chron's disease, GI bleeding or anemia
• Weight less than 110 lbs
• Renal insufficiency
• Any other factor that in the investigator's judgment may affect patient safety or compliance (e.g. distance greater than 100 miles from this facility);

Additional Exclusion Criteria for Depressed Subjects:

• Active suicidality or current suicidal risk as determined by the investigator