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 other autoimmune disorders. * Presence of an uncontrolled medical condition that is deemed by the investigators to interfere with the proposed study procedures, or to put the study participant at undue 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 weeks prior 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 aneurysm clips. Medications: * Current and/or past regular use of hormone-containing medications (excluding contraceptives) * Current use of non-steroid anti-inflammatory drugs that is deemed by the investigators to potentially confound the results of the study * Current and/or past regular use of immune modifying drugs that target specific immune responses such as TNF antagonists * Current use of analgesics such as opioids or history of addiction to opioids or other analgesics * Current and/or past regular use of cardiovascular medications, including antihypertensive, antiarrhythmic, anti-anginal, and anticoagulant drugs (does not apply where medications are taken for different purpose e.g. anti-hypertensives for migraine). * 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 following symptoms 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 msec If 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 translated from English, thus, non-English speaking volunteers will be excluded.