Rapid Antidepressant Dynamics in Acute Neuromodulation Treatments

The goal of this clinical trial is to learn how different types of non-invasive brain stimulation affect mood and brain function in adults with major depressive disorder (MDD). It will also study how brain stimulation may work together with antidepressant treatments. The main questions this study aims to answer are: How do different patterns of brain stimulation affect mood in people with depression? Do brain networks involved in emotion and self-reflection respond differently depending on the type of stimulation? What are the combined effects of brain stimulation and antidepressant treatments on mood and brain activity? Researchers will compare different brain stimulation patterns and target areas to understand their individual and combined effects. Participants will: Receive three types of brain stimulation (intermittent, continuous, and sham) in different sessions Undergo MRI scans during the administration of either a fast-acting or conventional antidepressant. Complete mood assessments during the scan and for one week after each session This study may help identify brain-based strategies to improve treatment for depression. In addition, a subset of participants (\~25) will complete a reward-guided decision-making fMRI task for feasibility purposes.

Inclusion criteria: 1. Adults ages 18-55 (\~60% female). 2. Diagnosis of Major Depressive Disorder (MDD) with or without comorbid anxiety disorders (e.g., panic disorder) or Axis II disorders. 3. Psychotropic-free at enrollment. Exclusion Criteria: 1. being pregnant or breastfeeding; 2. diagnosis of psychotic depression, schizophrenia, bipolar disorder, or other Axis I disorders, except for anxiety disorders; 3. severe substance use (excluding nicotine) in the last 2 months as determined by using the MINI, a structured interview that uses the Diagnostic and Statistical Manual of Mental Disorders; 4. requiring immediate hospitalization; 5. epilepsy or conditions requiring an anticonvulsant; 6. receiving vagus nerve stimulation, electroconvulsive therapy (ECT), or TMS in the last 2 months; 7. currently taking or have taken within the last 21 days psychiatric medication or augmenting agents; 8. receiving depression-specific psychotherapy; 9. actively suicidal or considered a high suicide risk; 10. enrolled in another study; or 11. MRI/TMS contraindication as determined by the fMRI and TMS screening questionnaires