Stress and Inflammation in Late-Life Depression

Stress and Inflammation in the Pathophysiology of Late Life Depression

Over 18% of Americans aged 65 years and older have depression. Recent evidence suggests that there is a link between depression and inflammatory disease. This study investigates the relationship between inflammation in the brain and depression. Comparing biological and psychological differences in depressed and non-depressed people allows researchers to find better ways to treat and prevent depression. All participants will have: neuropsychological tests, an EKG, a spinal tap, a blood draw, and, if depressed, given either an antidepressant coupled with an anti-inflammatory medication or an anti-depressant coupled with a placebo for six weeks. The investigators are trying to correlate brain function with depression levels and biomarkers from the blood and spinal fluid.

Inclusion Criteria:

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

Additional Inclusion Criteria for Depressed Participants:

1. DSM-IV criteria for Major Depressive Disorder
2. HAM-D greater than 18

Exclusion Criteria:

1. 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);
2. Does not speak English;
3. Cannot give informed consent;
4. MRI contraindications (e.g., foreign metallic implants, pacemaker);
5. Known primary neurological disorders, such as Parkinson's disease, Alzheimer's disease, traumatic brain injury, cognitive impairment or dementia,
6. 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.
7. Clinical Dementia Rating Scale score greater than 0;
8. Diagnosis of a chronic psychiatric illness other than MDD at the discretion of the study doctor;
9. Significant handicaps (e.g. uncorrected hearing or visual impairment, mental retardation) that would interfere with testing;
10. Bleeding diathesis;
11. Severe Medical problem, which in the opinion of the investigator would pose a safety risk to the subject;
12. 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;
13. Clinically significant abnormalities on EKG. Primary AV block or Right bundle branch block are not necessarily exclusionary;
14. Current diagnosis of cancer
15. Current diagnosis of HIV, active Hepatitis B and/or Hepatitis C
16. Use of an Investigational medicine within the past 30 days;
17. Use of Coumadin, Warfarin within the past 2 months;
18. 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;
19. Current alcohol or substance abuse disorder, schizophrenia or other psychotic disorder, bipolar disorder, or current OCD;
20. Abnormal liver-function test
21. History of ulcer disease, Chron's disease, GI bleeding or anemia
22. Weight less than 110 lbs
23. Renal insufficiency
24. 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:

1) Active suicidality or current suicidal risk as determined by the investigator