To facilitate the development of a personalized approach to the treatment of patients with major depression, this study is designed to elaborate the clinical and neurobiological phenotype of depressed patients with increased inflammation. The data obtained in this proposal will allow the investigators to test the hypothesis that depression and inflammation interact to elaborate a relatively discreet phenotype that warrants an individualized approach to diagnosis and treatment of patients with depression. Moreover, the identification of specific environmental risk factors for inflammation will foster the elaboration of preventative strategies for patients at risk.

One hundred and thiry-five patients with major depression diagnosed based on DSM-IV TR criteria between the ages of 21 and 65 (males, females and minorities) will be recruited. Forty-five patients with high inflammation as defined by a CRP >3 mg/L will be enrolled along with 45 depressed patients with medium inflammation (CRP=1-3mg/L) and 45 depressed patients with low inflammation (CRP<1mg/L) will complete a 2 night inpatient stay in Emory University Hospital's research unit, the Atlanta Clinical and Translational Science Institute (ACTSI). Participants will undergo psychiatric and neurocognitive assessments, sleep studies and blood and cerebral spinal fluid (CSF) sampling.

Inclusion Criteria:

• age 21-65 years including males, females and minorities
• diagnosis of DSM-IV major depression or Bipolar I or II with current episode of depression
• HDRS-17 > 20 and HDRS-24 > 24
• negative pregnancy test for women of childbearing potential
• not breast feeding
• stable on current dose of psychotropic medication or free from all psychotropic medications for 4 weeks prior to EUH CIN admission (8 weeks for fluoxetine)
• no suicide attempt within six months of screening

Exclusion Criteria:

• evidence of untreated or poorly controlled endocrine, cardiovascular, pulmonary, hematological, renal, or neurological disease
• history of CNS trauma or active seizure disorder requiring medication unless otherwise approved by principle investigator
• autoimmune or inflammatory disorder of any kind
• chronic infection (e.g. hepatitis B or C or HIV)
• chronic use of agents known to affect the immune system including glucocorticoid therapy within the past 1 year, methotrexate within the past 1 year, chemotherapy of any kind (past or present), immunotherapy of any kind (past or present), aspirin or non-steroidal anti-inflammatory drugs (NSAIDs) (within the past 2 weeks) and statins (within the past 1 month) unless otherwise approved by principle investigator
• hemoglobinopathies (e.g. thalassemia)
• a positive pregnancy test
• organ transplants
• cancer of any type
• a score of <28 on the Mini Mental Status Exam (MMSE)unless otherwise approved by principle investigator
• meets criteria for schizophrenia (Given overlap of generalized anxiety disorder (GAD) with major depression, GAD will not be exclusionary)
• current eating disorders
• active abuse of alcohol or illicit/prescription drugs within the past year unless otherwise approved by principle investigator.
• MGH-S >3 unless otherwise approved by principle investigator
• BMI >40 unless otherwise approved by the principle investigator
• active suicidal intent or plan and a score >2 on the HDRS suicide item (item #3).
• any other condition which in the opinion of the investigator would make the patient unsuitable for enrollment, or could interfere with participating in or completing the protocol

One hundred and thiry-five patients with major depression diagnosed based on DSM-IV TR criteria between the ages of 21 and 65 (males, females and minorities) will be recruited. Forty-five patients with high inflammation as defined by a CRP >3 mg/L will be enrolled along with 45 depressed patients with medium inflammation (CRP=1-3mg/L) and 45 depressed patients with low inflammation (CRP<1mg/L)