Personalized Ultrasonic Brain Stimulation for Depression (R61)

Eligibility Criteria

• 1. Age 18-65, any gender.
• 2. Primary diagnosis of DMS-5 major depressive disorder (MINI).
• 3. Current moderate-to-severe depressive episode, without psychotic features, lasting at least 2 months (MINI).
• 4. Self-rated 16-item Quick Inventory of Depressive Symptomatology (QIDS) total score \> 10.
• 5. History of at least 2 failed trials of evidence-based antidepressant medication and/or psychotherapy (at least one trial during the current depressive episode).
• 6. Stated willingness to comply with all study procedures and avoid changes to psychiatric treatments (medications, psychotherapy) for the duration of the study.
• 7. For participants of reproductive potential: negative pregnancy test or use of highly effective contraception for at least 1 month prior to baseline; agreement to use such a method throughout the study.
• 8. Capacity to provide informed consent; provision of a signed and dated consent form
• 9. Currently are under the care of a licensed psychiatrist or other mental health care provider, or a licensed addiction medicine specialist and agrees to promptly inform the investigator or the study staff of any change in these providers.
• 10. Agrees to allow any and all forms of communication between the investigators/study staff and any healthcare provider who currently provides and/or has provided service to the patient/subject within at least two years of study enrollment for the purposes of eligibility confirmation or in case of a safety event.
• 11. Agrees to provide the name and verifiable contact information (email and mailing addresses, mobile and land-line phone numbers, as applicable) of at least two persons 22 years or older who reside within a 60-minute drive of the patient's residence. Subject agrees that in the event of a safety concern or event during study participation, research staff is at liberty to contact these individuals if the subject does not respond to contact attempts.
• 1. History of serious brain injury or other neurologic disorder.
• 2. Poorly managed general medical condition.
• 3. Pregnant or breast feeding.
• 4. Implanted device in the head or neck.
• 5. MRI intolerance or contraindication.
• 6. Brain stimulation treatment such as ECT, TMS, or VNS (past month).
• 7. Recent change in antidepressant treatments (past month).
• 8. 8. Moderate-High Risk of Suicide according to the Columbia - Suicide Severity Rating Scale (C-SSRS) Screen Version - Recent (answers YES to Question 3 and NO to Question 6 (Moderate risk) or YES to Question 4, 5, or 6 (High risk)) and/or in the clinical judgement of the PI or a study psychiatrist
• 9. Suicidal behavior (past year).
• 10. Serious suicide attempt 33 (lifetime).
• 11. Moderate-to-severe substance use disorder (MINI, past 3 months).
• 12. Obsessive compulsive disorder, primary diagnosis (MINI, past month).
• 13. Posttraumatic stress disorder, primary diagnosis (MINI, past month).
• 14. Bipolar-spectrum disorder (MINI, lifetime).
• 15. Schizophrenia-spectrum disorder (MINI, lifetime).
• 16. Neurocognitive disorder (DSM-5, past year).
• 17. Severe personality disorder.
• 18. Clinically inappropriate for participation in the study as determined by the study team.