Inclusion Criteria:
1. Capacity to provide consent, and informed consent provided
2. Diagnosis of bipolar I disorder and currently meet criteria for DSM5 major depressive episode
3. Depression at enrollment of sufficient severity to score at least 16 on the first 17 items of the Hamilton Depression Rating Scale when including the atypical depression items addendum
4. Age 18-60 years old
5. Patients who are on antidepressant (SSRI, SNRI or bupropion) or antipsychotic medications at presentation will be included if they have failed that regimen, as defined as not achieving at least partial remission after an adequate dose of medications for at least four weeks. Fluoxetine will not be allowed due to its long half-life. Patients will be able to continue to take other mood stabilizer medications (lamotrigine, lithium, valproate, carbamazepine or oxcarbazepine) if they had not made changes to the dose of those medications within eight weeks of signing consent. Benzodiazepines and hypnotics are allowed throughout the study. If taking stimulant medications, they must be willing not to take these during the study.
6. Females of child-bearing potential must be willing to use an acceptable method of birth control throughout the study; abstinence if it does not require changes to usual behavior, birth control pill, male condom, IUD, dep- provera, norplant, male sterilization or female sterilization are acceptable.
7. Participant is likely to tolerate medication washout if indicated
Exclusion Criteria:
1. Diagnosis of any other major psychiatric disorders such as schizoaffective disorder, current psychotic depression. Any recent drug or alcohol use disorder; within 3 months before the study unless mild. Participant meets DSM5 criteria for manic episode at the time of screening, or has YMRS \> 12.
2. Previous failed trial of cariprazine, defined by at least six weeks of treatment at the dose of 1.5 mg per day or more. Experienced intolerable side effects of cariprazine in the past. Taking any medications that are either contraindicated or that have clinically significant drug-drug interactions (such as strong CYP3A4 inducers) with cariprazine, unless there is a plan to stop these as part of the washout.
3. History of clinical deterioration when any of the medications that the participant is taking at presentation have been discontinued in the past if they will be discontinued as part of the washout.
4. First-degree family history of schizophrenia if the participant is less than 33 years old.
5. Significant active physical illness, including blood dyscrasias, lymphomas, hypersplenism, endocrinopathies, renal failure, chronic obstructive lung disease, autonomic neuropathies, peripheral vascular disease, neuromuscular disorder or tardive dyskinesia. Any medical diagnoses that would be a contraindication to cariprazine treatment, including any movement disorders. Any history of a seizure disorder.
6. Actively suicidal, as defined by expressive ideation with a plan and intent for suicide, or developing suicidal ideation that requires immediate medical or treatment intervention.
7. Active lactation
8. Electroconvulsive therapy within the past 6 months
9. Participants who endorse a history of prior head trauma and score 1.5 standard deviations below the mean of Trailmaking A \& B test
10. Metal implants, cardiac pacemaker, metal prostheses, metal orthodontic appliances or shrapnel in the body unless there is confirmation that the substance is MRI compatible
11. Current, past or anticipated exposure to radiation, including:
A. Having been badged for radiation exposure in the workplace B. Participation in nuclear medicine protocols in the past year. However, participants will be eligible if the injected dose and dosimetry of the radiotracer used are known and the cumulative annual exposure of the previous study and this study is lower than the annual limit for research participants defined by FDA (21 CFR 361.1)
12. History of claustrophobia that would prevent participation in imaging scans.
13. Inadequate understanding of English
14. Weight \>350 lbs or inability to fit into the MRI scanner
