Tractography Guided Subcallosal Cingulate Deep Brain Stimulation for Treatment Resistant Depression

Inclusion Criteria: * Men and women (non-pregnant) between ages 21 and 70; * DSM-5 diagnosis a current major depressive episode (MDE) for 10 years of less, recurrent or single episode with first episode after adulthood and did not start during childhood or adolescence, secondary to nonpsychotic unipolar major depressive disorder; * Current index MDE ≥24 months duration and/or recurrent illness with at least a total of 2 lifetime episodes (including current episode \>12 months); * Treatment resistance (defined by criteria on the Antidepressant Treatment History Form (ATHF)28): Failure to respond to a minimum of four adequate depression treatments from different categories; * Symptom severity for Screening: Hamilton Depression Rating Scale-17 item (HDRS17) ≥20; * Symptom severity for Outcome: Montgomery Asberg Rating Scale (MADRS) ≥27 to be met at assessment one week pre-op; * Normal brain MRI within 3 months of surgery; * Antidepressant medication regimen has been held stable for ≥ 30 days prior to the study screening MADRS; * Remain on stable antidepressant medication throughout the study, unless there are safety concerns; * Montreal Cognitive Assessment (MoCA) \>25; * Able and willing to give informed consent and agree to attend regular clinic visits for at least 12 months. Exclusion Criteria: * DSM-5 Axis I Disorders: any lifetime history of psychotic disorder or bipolar disorder; * Alcohol or substance use disorder within 6 months, excluding nicotine; * History of childhood abuse (physical or sexual) 18 * Personality disorders; * Seeking disability during the trial; * Current substantial suicidal risk as defined by a plan or clear immediate intent for self-harm, or made any suicide attempt within the last year; (MADRS ≥ 5 including the day of surgery); * No stable work history; * Neurological/Medical condition that makes the patient, in the opinion of the surgeon, a poor candidate; 1. Pregnant or has plans to become pregnant in the next 36 months; 2. Unable/unable to practice birth control through the period of randomization and withdrawal of therapy; * Subjects who have a history of a seizure disorder; * Subjects who will be exposed to diathermy; * Subjects who have any medical contraindications to undergoing DBS surgery (e.g. infection, coagulopathy, or significant cardiac or other medical risk factors for surgery); * Subjects with another implanted device such as a cardiac pacemaker, defibrillator or neurostimulator; * Subjects who have a history of hemorrhagic stroke; * Subjects who are unable to undergo MRI; * Subjects who are at increased risk of hemorrhage due to underlying medical conditions or medication.