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:
• screening supine systolic blood pressure >140 mmHg or 90 mmHg or 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
• pulse less than 50 beats/minute or greater than 100 beats/minute
• 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.