Personalized Ultrasonic Brain Stimulation for Depression (R61)

This R61 project has 3 aims:

• To determine whether stimulation engages the subcallosal cingulate (SCC) in an intensity-dependent manner
• To examine the degree of specificity of neuromodulation by contrasting the neural effects of stimulating two spatially distinct targets versus sham
• To evaluate safety, tolerability, and side effects

Inclusion criteria

• Age 18-65, any gender.
• Primary diagnosis of DMS-5 major depressive disorder (MINI).
• Current moderate-to-severe depressive episode, without psychotic features, lasting at least 2 months (MINI).
• Self-rated 16-item Quick Inventory of Depressive Symptomatology (QIDS) total score > 10.
• History of at least 2 failed trials of evidence-based antidepressant medication and/or psychotherapy (at least one trial during the current depressive episode).
• Stated willingness to comply with all study procedures and avoid changes to psychiatric treatments (medications, psychotherapy) for the duration of the study.
• 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.
• Capacity to provide informed consent; provision of a signed and dated consent form
• 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.
• 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.
• 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.

Exclusion criteria

• History of serious brain injury or other neurologic disorder.
• Poorly managed general medical condition.
• Pregnant or breast feeding.
• Implanted device in the head or neck.
• MRI intolerance or contraindication.
• Brain stimulation treatment such as ECT, TMS, or VNS (past month).
• Recent change in antidepressant treatments (past month).
• 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
• Suicidal behavior (past year).
• Serious suicide attempt 33 (lifetime).
• Moderate-to-severe substance use disorder (MINI, past 3 months).
• Obsessive compulsive disorder, primary diagnosis (MINI, past month).
• Posttraumatic stress disorder, primary diagnosis (MINI, past month).
• Bipolar-spectrum disorder (MINI, lifetime).
• Schizophrenia-spectrum disorder (MINI, lifetime).
• Neurocognitive disorder (DSM-5, past year).
• Severe personality disorder.
• Clinically inappropriate for participation in the study as determined by the study team.