Lipopolysaccharide (LPS) Challenge in Depression

Inclusion Criteria:

Depressed participants will be required to be in good general health (as evaluated during Visit 1, including EKG) and to be 18-55 years of age. Depressed participants will be required to have symptoms of depression (i.e. a PHQ-9 score ≥10) and be unmedicated for at least 3 weeks (8 weeks for fluoxetine) or treated with only one anti-depressant medication. Half the depressed participants (N=50) will be required to have a high-sensitivity C-Reactive Protein (CRP) score of ≥3 mg/L, and half the participants will be required to have a CRP score of ≤1 mg/L.

General Exclusion Criteria:

• Pregnancy

• Previous history of fainting during blood draws.

Medical Conditions:

• A history of a head injury with loss of consciousness.

• Presence of co-morbid medical conditions not limited to but including cardiovascular (e.g., history of acute coronary event, stroke) and neurological diseases (e.g.,Parkinson's disease), as well as pain disorders.

• Presence of co-morbid inflammatory disorders such as rheumatoid arthritis or otherautoimmune disorders.

• Presence of an uncontrolled medical condition that is deemed by the investigators tointerfere with the proposed study procedures, or to put the study participant atundue risk.

• Presence of chronic infection that may elevate pro-inflammatory cytokines.

• Presence of an acute infectious illness or receipt of a vaccination in the two weeksprior to an experimental session.

Psychiatric Disorders:

• Current severe suicidal ideation or attempt within the past 12 months.

• Psychosis

• Bipolar disorder

• Substance abuse or dependence within the previous 6 months

• Age of onset of depression >40 years

Contraindications for MRI:

• Severe claustrophobia

• Bodily implants of unsafe paramagnetic materials such as pace-makers and aneurysmclips.

Medications:

• Current and/or past regular use of hormone-containing medications (excludingcontraceptives)

• Current use of non-steroid anti-inflammatory drugs that is deemed by theinvestigators to potentially confound the results of the study

• Current and/or past regular use of immune modifying drugs that target specificimmune responses such as TNF antagonists

• Current use of analgesics such as opioids or history of addiction to opioids orother analgesics

• Current and/or past regular use of cardiovascular medications, includingantihypertensive, antiarrhythmic, anti-anginal, and anticoagulant drugs (does notapply where medications are taken for different purpose e.g. anti-hypertensives formigraine).

• Evidence of recreational drug use from urine test.

• Lifetime use of methamphetamine

Health Factors:

• BMI > 35 because of the effects of obesity on pro-inflammatory cytokine activity

• Clinically significant abnormalities on screening laboratory tests

• Abnormal EKG

• In addition, participants who on arrival to the study, show any of the followingsymptoms will not be allowed to complete the study:

1. screening supine systolic blood pressure >140 mmHg or <100 mmHg

2. screening supine diastolic blood pressure >90 mmHg or <60 mmHg

3. 12-lead EKG demonstrating a PR interval > 0.2 msec, QTc >450 or QRS >120 msecIf the QTc exceeds 450 msec, or QRS exceeds 120 msec, the EKG will be repeated 2 more times and the median value will be used

4. pulse less than 50 beats/minute or greater than 100 beats/minute

5. temperature greater than 99.5F.Non-English speaking participants:

• The majority of the assessments proposed for this study have not been translatedfrom English, thus, non-English speaking volunteers will be excluded.