Lipopolysaccharide (LPS) Challenge in Depression

The aim of this project is to understand the biological differences between two distinct
subtypes of depression, patients with and without inflammation as defined by c-reactive
protein (CRP). Using a double-blinded, parallel group, placebo-controlled design,
participants will be phenotyped before and after a low-dose lipopolysaccharide (LPS)
challenge designed to perturb the immune system and trigger a transient, mild inflammatory
response. This experimental design will allow for the delineation of the homeostatic
mechanisms underlying sensitivity to inflammation-related depression. Low-dose LPS has been
used by multiple groups to safely induce transient inflammatory responses in humans. The
pilot study is expected to take approximately one year to complete.

Inclusion Criteria:

- Both healthy controls and 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).
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.

Exclusion Criteria:

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 lifetime history of a suicide attempt

- 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 regular use of non-steroid anti-inflammatory drugs

- 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

- Current use of cardiovascular medications, including antihypertensive, antiarrhythmic,
anti-anginal, and anticoagulant drugs.

- Evidence of recreational drug use from urine test.

Health Factors:

- BMI > 35

- 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: (a) blood pressure less than 90/60
or greater than 140/100, (b) pulse less than 50 beats/minute or greater than 100
beats/minute, and (c) temperature greater than 99.5°F.

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.