The goal of the study is to validate a biomarker assay for unipolar depression based on serum proteins involved in inflammation, metabolism, and stress response. The study will compare patients with a current major depressive episode to individuals with no history of depression. The hypothesis is that the assay can serve as a diagnostic tool that would be more objective than standard diagnostic questionnaires.

Inclusion Criteria (Depressed):

• Aged 18 to 60.
• Meets DSM-IV criteria for Unipolar Major Depression, either single or recurrent.
• 21 item Hamilton Depression rating scale score greater than 18.
• Capable of providing informed consent.
• Has an established residence and phone number.

Exclusion Criteria:

• Meets DSM-IV criteria for Bipolar Disorder, Schizophrenia, Schizoaffective disorder or other major Axis I Psychiatric disorders (except for depression and phobia per above).
• Addison's Disease, Cushing's Disease, or other known dysfunction of the HPA-cortisol axis.
• Rheumatoid arthritis, lupus, or other condition associated with increased inflammation.
• Regular use of non-steroidal anti-inflammatory medications, steroids, or other medications know to interact with the inflammatory process of the HPA axis.
• A medical condition or regular use of a mediation, which I the opinion of the investigator is likely to influence the inflammatory or HPA responses.
• Pregnancy.
• Meets DSM-IV criteria for substance abuse or dependence in the last month.
• Regular cigarette smoking.
• History of fainting or other significant adverse event during blood drawing in the past.

Subjects are recruited from the community by advertisement.