Depression, Obesity and Inflammatory Markers

Aim 1 will examine relationships between the levels of the inflammatory markers and current
clinical state (depressed, manic or euthymic) with the hypothesis that Inflammatory markers
will be higher in depression and mania relative to the euthymic state.

Aim 2 will examine relationships between inflammatory markers and BMI in bipolar patients
with the hypothesis that inflammatory markers will correlate positively with BMI.

Aim 3 will examine the relationship between depression, obesity and inflammatory markers with
the hypothesis that depressed (or manic) bipolar patients who are also obese will have higher
inflammatory markers than either obese euthymic patients or non-obese depressed or manic
patients.

Aim 4. The pilot study will be to conduct a proof of concept add-on treatment study of the
antibiotic minocycline for bipolar patients who are depressed, likely to be obese and likely
to have elevated inflammatory markers and increased risk of heart disease. This is a proposal
to conduct a 2-site trial of 50 subjects to examine the value of minocycline augmentation in
bipolar depressed patients who are incompletely responsive to initial treatment with anti
depressants and/or mood stabilizers. The investigators will compare two subgroups of
depressed patients, those who have high (N=25) versus those who have low (N=25) levels of
C-reactive protein (CRP) as defined below.

Inclusion Criteria:

- Patients with Bipolar Disorder and current depressive symptoms

- Hamilton Depression Scale score > 18

- Failed an adequate trial of at least one antidepressant or mood stabilizer of at least
4 weeks duration. Medication history will be recorded using the Antidepressant
Treatment History Form

- 18 years or older

- Fluent in English or Arabic

- Have the capacity to understand the nature of the study and sign the written informed
consent.

Exclusion Criteria:

- A current diagnosis of Schizophrenia or other psychotic disorder, or Dementia
Alzheimer Type or related cognitive disorders.

- Principal diagnosis of Post-Traumatic Stress Disorder, Anorexia or Bulimia Nervosa,
Obsessive-Compulsive Disorder. We define principal as the most pressing clinical
problem.

- Pregnant or nursing

- Axis II diagnosis of antisocial, schizotypal or severe borderline personality disorder
(defined as patients who are high risk for being unable to complete the study due to
hospitalization, suicide attempts, significant self-mutilation, or other
self-injurious or destructive behavior).

- Patients who currently meet criteria for Alcohol or other Substance-Related Dependence
Disorder (with the exception of nicotine dependence) who require detoxification.

- Patients who are unable to read and write English or Arabic.

- Patients having serious, unstable or terminal medical or neurologic illness that would
compromise study participation (i.e., metastatic or advanced malignancy, chronic renal
failure requiring dialysis, recent myocardial infarction or unstable angina, or "end
stage" chronic obstructive pulmonary disease). People with common conditions such as
hypertension, insulin dependent diabetes mellitus, asthma, compensated congestive
heart failure, a malignancy in remission, treated hypothyroidism, or epilepsy will not
be excluded from participation.

- Autoimmune disease or chronic inflammatory diseases such as psoriasis or Crohn's
disease

- Chronic infection such as hepatitis B or C or HIV

- Elevated antinuclear antibody or rheumatoid factor

- Oral glucocorticoids in the past 6 months

- Methotrexate or NSAID use in the past two weeks