You are being asked to take part in this research study because you have been diagnosed with bipolar disorder and are currently experiencing a depressive episode. Bipolar disorder is an illness characterized by recurrent mood swings including mania, (periods of elation, excessive excitement, irritability, high energy, racing thoughts, poor sleep, poor judgment, reckless behavior) and clinical depression (periods of depressed mood, loss of interest in activities and disruption of sleep, appetite and energy). To participate in this study you must be at least 16 years old, and no older than 35.

Inclusion Criteria - Depressed bipolar patients (N=80; 15-20 patients/year):

1. Patients will meet DSM-IV criteria for type I bipolar disorder, depressed, as determined by structured interview and best-estimate diagnostic procedures.138
2. Patients will have no history of any Axis I psychiatric disorder except for bipolar disorder.
3. Patient has experienced a maximum of three documented affective episodes.
4. Patient has been off medications for ≥ two weeks (or five half-lives, whichever is longer) prior to study enrollment.
5. Patient has a Hamilton Depression Rating Scale (HDRS) total score ≥20 and a Young Mania Rating Scale (YMRS) total score ≤12.140,141,160
6. Patient is between the ages of 16 and 35 years.

Inclusion Criteria - Healthy subjects (N=40; 8-10 subjects/year):

1. Healthy subjects will be between the ages of 16 and 35 years.
2. Healthy subjects will have no history of any Axis I psychiatric disorder.
3. Healthy subjects will have no first- or second-degree relatives with affective or psychotic disorders.

Exclusion criteria: All subjects will be excluded from participation for the following reasons:

1. Any history of alcohol or drug dependence, and any alcohol or drug use disorder within 3 months.
2. Any history of significant suicidality that would place the patient at risk to participate in this protocol.
3. Current score ≥3 on item 3 of the HDRS-17 (Suicide Item)
4. Any medical or neurological disorder that could influence fMRI results.
5. A history of mental retardation or an estimated IQ total score <85.
6. An MRI scan is contraindicated in the subject for any reason.
7. The patient lives >100 miles from the University of Cincinnati or cannot attend follow-up visits.