The purpose of this study is to better understand the relationship between bipolar disorder, body weight, and inflammation in the body (N=180). People with bipolar depression (N = 50)will be offered a place in a pilot study looking to see if the antibiotic minocycline added to current psychiatric medications has an effect on mood. A separate consent form will be provided for the pilot study. Numerous studies have documented the presence of altered immune function and elevation of inflammatory markers in patients with depression. Studies suggest that major depression is accompanied by immune dysregulation and activation of the inflammatory response system. While a small number of studies have found elevated inflammatory markers in bipolar mania, very little has been reported about inflammation in bipolar depression, and none of these studies have addressed the relationship of inflammatory markers with obesity in bipolar disorder.

Aim 1 (N=180)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 (N=180)will examine relationships between inflammatory markers and BMI in bipolar patients with the hypothesis that inflammatory markers will correlate positively with BMI.

Aim 3 (N=180)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. (N=50) 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).

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

Individual Participant Data will not be shared.

8 weeks

Three participants not evaluated due to early withdrawal from the study