Comparing Outcomes of Theta Burst Stimulation in Depression Using Advanced PET Imaging

Prior treatment

• Contraindication for MRI (e.g. metallic implant, claustrophobia).
• Have received a cumulative radioactivity dose \> 15.2mSv during the last 12 months.
• Benzodiazepine or lithium use. Other psychotropic medications (e.g. ADHD medications) are permitted, if stable in the 4 weeks prior to and during the treatment course)

Other illness

• Any comorbid mental health disorders (including, but not limited to lifetime history of psychotic disorders, OCD, and/or bipolar I or II disorder) with the exception of anxiety/panic disorders, posttraumatic stress disorder and ADHD
• Significant unstable medical or neurologic illness confirmed by medical history (e.g. uncontrolled diabetes, or renal dysfunction).
• Contraindication for TMS (e.g., personal history of epilepsy or convulsion, metallic head implant, pacemaker).
• Have active malignancies (due to high chance of undergoing radiation therapy).
• Any other condition that, in the opinion of the investigators, would adversely affect the participant's ability to complete the study.

Other

• Participants fulfilling any of the following criteria will be excluded from the study:
• Current or past (\< 3 months) substance (including nicotine) or alcohol abuse/dependence, as defined in DSM-5 criteria.
• Positive urine test for illegal substances, cannabis, or cotinine.
• Breastfeeding or pregnant (confirmed via urine test).
• BMI \> 30 or BMI \< 18.
• Suicide attempt in the past three months and/or active suicidal intent.
• Failed (non-response) course of ECT or rTMS treatment in the current depressive episode.

• For inclusion in the study, participants must fulfill all the following criteria:
• 18 to 55 years old.
• Competent to provide voluntary informed consent.
• English comprehension and verbal communication (participants must be able to both understand and speak English sufficiently to follow study procedures and be understood by study personnel
• Referred by their treating physician.
• Mini-International Neuropsychiatric Interview-confirmed diagnosis of MDD, as a single or recurring episode.
• Symptoms of MDD have not improved after ≥ 1 adequate antidepressant medication trial in the current depressive episode29.
• Baseline score of ≥18 on the 17-item Hamilton Rating Scale for Depression (HRSD-17).
• Maintained a stable treatment regimen for at least four weeks prior to entering the study, defined as being on a stable antidepressant regimen, a stable psychotherapy regimen, both, or neither (i.e., no treatment), with no changes during this period.