Inflammation-related Alterations in Neurocircuitry: Reversal With Levodopa

Cytokines released by an activated immune system have been associated with decreased brain
dopamine and the development of depression. Biomarkers of inflammation, such as inflammatory
cytokines and acute-phase proteins like C-reactive protein (CRP), are elevated in a
significant proportion of patients with mood and psychiatric disorders. The investigators
will study if administration of Levodopa (L- 3,4-dihydroxyphenylalanine [DOPA]-carbidopa,
250/25mg) to depressed patients with high inflammation will 1) increase corticostriatal
functional connectivity, and 2) improve objective measures of motivation compared to placebo.

Inclusion Criteria:

- Subjects have signed a current version of the Informed Consent and HIPAA documents
prior to initiation of study procedures

- Diagnosis of Diagnostic and Statistical Manual of Mental Disorders (DSM)-IV major
depression and currently off antidepressant medication, unless otherwise approved by
the PI or PI's designee

- Hamilton Depression Rating Scale (HDRS) 17 > 20, unless otherwise approved by the PI,
or PI's designee

- Negative pregnancy test for women of childbearing potential

- Not breast feeding

Exclusion Criteria:

- Evidence of untreated or poorly controlled endocrine, cardiovascular, pulmonary,
hematological, renal, or neurological disease

- History of central nervous system (CNS) trauma or active seizure disorder requiring
medication unless otherwise approved by principal investigator, or PI's designee

- Current or history of migraines, glaucoma, melanoma, or bleeding disorder of any kind

- Autoimmune or inflammatory disorder of any kind

- Embedded metallic objects, prosthetics made of paramagnetic metals, aneurysmal clips
and/or a history of claustrophobia

- Chronic infection (e.g. hepatitis B or C or Human Immunodeficiency Virus infection)

- Chronic use of agents known to affect the immune system including glucocorticoid
therapy within the past 6 months, 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), statins
(within the past 1 month), vaccinations (within the past 2 weeks), topical steroids
(within the past 2 weeks), and antibiotics (within the past two weeks) unless
otherwise approved by principal investigator or PI's designee.

- Suicide attempt within six months of screening, or active suicidal intent or plan, or
score >2 on Hamilton Depression Rating Scale (HDRS) Suicide Item, unless otherwise
approved by the PI or PI's designee

- A positive pregnancy test

- Organ transplants

- Current or history of cancer within the past five years besides basal cell carcinoma,
unless otherwise approved by the PI or PI's designee

- A score of <28 on the Mini Mental Status Exam (MMSE), unless otherwise approved by the
PI or PI's designee

- Wide Range Achievement Test (WRAT-3) score indicating less than 8th grade reading
level, unless otherwise approved by the PI or PI's designee

- History of the following: schizophrenia, schizoaffective disorder, other (non mood
disorder) psychosis, depression secondary to a medical condition, mental retardation,
dementia, or delirium

- Substance dependence [or abuse within the past year (except nicotine)], unless
otherwise approved by the PI or PI's designee

- Body Mass Index >40 to limit the impact of morbid obesity on the results, unless
otherwise approved by the principal investigator or PI's designee

- Active suicidal intent or plan and a score >2 on the Hamilton Depression Rating Scale
suicide item (item #3).

- Antisocial personality disorder diagnosis as assessed during clinical interview, as
well as a history of hospitalization and/or recurrent suicidal behavior judged to be
directly due to the personality disorder

- Current eating disorder (except binge eating related to depression) unless approved by
PI or PI's designee

- 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

- Smoking more than 1/2 pack a day or e-cig equivalent, unless approved by the PI or
PI's designee

- Initiation of any of the following medications, unless otherwise approved by the PI or
PI's designee: Aspirin or Aspirin-like compounds, Ibuprofen or Naproxen Sodium,
Cholesterol medications, Antibiotics, Herbal Medications, Psychiatric or Psychotropic
Medications, Omega-3 supplements, Topical Steroids, Vaccinations

- Currently on antidepressant medication, unless otherwise approved by the PI or PI's
designee