Dopaminergic Effects of Adjunctive Aripiprazole on the Brain in Treatment-Resistant Depression

Treatment Group Inclusion Criteria: 1. Subjects with known history of MDD verified using the Mini International Neuropsychiatric Interview and a Hamilton Depression Rating Scale 17-item score of at least 18 2. Subjects must have failed to respond to one previous adequate dose-duration trial of antidepressant therapy 3. Must complete the MRI screening tool and demonstrate ability to receive an MRI 4. For entry into the ARP augmentation phase the subject must be a non-responder to the escitalopram phase as demonstrated by a MADRS score at week 10, that is not reduced by greater than 50% from baseline. Exclusion Criteria: 1. Subjects cannot be smokers 2. No significant history of anxiety disorder 3. Cannot be pregnant or lactating and sexually active women of childbearing potential must use a medically accepted means of contraception 4. The following DSM-IV diagnoses are excluded: Organic mental disorder; substance abuse/dependence, including alcohol, active within the last year; schizophrenia, paranoid or delusional disorders; other psychotic disorders; panic disorder; generalized anxiety disorder; obsessive-compulsive disorder, or post-traumatic stress disorder; bipolar disorder; bulimia nervosa; anorexia nervosa 5. Subjects with serious suicidal risks 6. Subjects who have taken any antidepressant medication other than escitalopram within 5 half lives, of the most recent antidepressant taken 7. Subjects involved in any other form of treatment for depression 8. Subjects who have demonstrated any previous inadequate antidepressant response to electroconvulsive therapy (ECT) 9. Subjects who have received ECT for the current depression episode 10. Subjects who have been hospitalized within 4 weeks of the study 11. Subjects who have received treatment with a monoaminoxidase inhibitor within 2 weeks of enrollment 12. Subjects with a known allergy, hypersensitivity, or previous unresponsiveness to aripiprazole or known intolerance to any study medications 13. Subjects with a history of participation in any investigational medication trial in the past month 14. A positive drug screen or substance use disorder in the past 12 months 15. History of any thyroid pathology 16. History of serotonin syndrome or neuroleptic malignant syndrome 17. History of seizure disorder 18. Subjects who have participated in a trial using PET scans in the past 12 months and in any trial in the past 30 days. Control Group Inclusion Criteria: 1. Ages 18-55 matched to a study subject 2. Must be a healthy subject with no significant medical history 3. Must complete the MRI screening tool and demonstrate ability to receive an MRI Exclusion Criteria: 1. Cannot be a smoker 2. Cannot be pregnant or lactating and sexually active women of childbearing potential must use a medically accepted means of contraception 3. Any DSM-IV or II diagnosis as assessed by the MINI 4. Subjects with a positive drug screen or substance use disorder in the past 12 months