Inclusion Criteria:

• Diagnosed with BPI, BPII, or MDD, confirmed with the Structured Clinical Interview for DSM-IV (SCID) and a consensus meeting of the study team.
• Currently depressed for ≥8 weeks and ≤104 weeks, without psychotic features,
• MADRS score ≥ 20 (consistent with at least moderate-severe depression)
• YMRS score ≤ 8 (consistent with the absence of hypomanic symptoms)
• Aged 18-70
• Capacity to understand the nature of the study and give informed consent
• BP patients must be enrolled in the Bipolar Biobank before or within 1 week of enrolling to this study and obtaining blood samples for proteomic study.
• MDD patients must consent to get their blood samples for proteomic and genomic analyses..

Exclusion Criteria:

• At high risk for suicide, defined as a score ≥4 on item 10 of the MADRS
• Current depression has psychotic features, diagnosed with the SCID
• Partially-treated current depression, defined as a change in treatment for depression (new treatment or change in dose of pre-existing treatment) in the past 4 weeks
• Treated with electroconvulsive therapy (ECT), transcranial magnetic stimulation (TMS), or clozapine in the past 6 months
• Meeting criteria for substance use disorders, as defined by DSM-IV, in the past 3 months, except for caffeine or nicotine. (Limited substance use, not meeting criteria for substance use disorders, is not exclusionary). A positive drug screen will also be exclusionary.
• Medical conditions with neurological sequelae (eg. stroke, brain cancer, multiple sclerosis, loss of consciousness > 30 min, HIV)
• Severe chronic pain requiring treatment with opiate analgesics
• Receiving treatment with high-potency immune-modulating medications, such as corticosteroids, chemotherapy, monoclonal antibodies, or disease-modifying agents for arthritis, multiple sclerosis
• Any acute unstable medical illness (at the discretion of the investigator)
• In MDD patients: strong risk factors for bipolarity, including 1) short (1-3 day) mood elevations not meeting DSM-IV time criteria for hypomania; 2) a family history of BDI or BDII in a first-degree relative; and 3) a history of antidepressant-induced symptoms suggestive of bipolarity, particularly antidepressant-induced hypo/mania.
• In females: pregnancy (as determined by a positive urine pregnancy test within 7 days of the baseline blood sample collection).