Veterans with treatment resistant depression (TRD) have the opportunity to receive transcranial magnetic stimulation (TMS) treatment via the VA's National TMS Clinical Pilot Program. While some see improvement with their depression, others do not. Therefore, it may be beneficial to be able to predict with biomarkers what participants may see improvement with their treatment. Electroencephalography (EEG) is a means to identify such biomarkers. Four hundred Veterans with TRD will be enrolled in this trial to determine whether neuroimaging biomarkers of repetitive transcranial magnetic stimulation (TMS) can be prospectively replicated in a large ecologically valid sample. Participants will have a total of EEG scans at baseline, every 5th treatment session, and at the end of treatment for a total of 7 EEG scans.

The goals of this study are to: (1) test a potential predictive resting EEG biomarker of antidepressant response (differential patters of gamma oscillations) in a large sample of Veterans with TRD receiving TMS (N=400); (2) assess whether a second putative biomarker (early changes in theta cordance during treatment) predict eventual response to TMS, as well as, leverage this large sample to identify other potential biomarkers (such as markers of early versus late response to TMS, markers of response to other TMS parameters (e.g., 5 Hz, 1 Hz or theta burst TMS), and markers of change with treatment that may speak to mechanism); and (3) create an infrastructure to rapidly identify and test additional EEG-based biomarkers of treatment response in patients with depression and other psychiatric conditions.

Inclusion Criteria:

• Veterans participating in the VA TMS Pilot Program age 18 years or older
• Able to provide written informed consent to participate in the EEG portion of this study and to allow linking such data to data collected as part of the TMS Pilot Program
• Diagnosis of MDD based on DSM-5 criteria and be currently depressed despite prior treatment with at least one adequate antidepressant treatment
• Receiving stable doses of psychiatric medications (no dose changes for >4 weeks prior to study entry), in stable psychotherapy, or receiving no psychiatric medications and/or psychotherapy

Exclusion Criteria:

• History of seizure disorder
• Known structural or neurologic abnormalities present or close to the treatment site that would increase risk of seizure
• History of brain surgery
• History of recent traumatic brain injury (within 6 months) or any history of moderate to severe traumatic brain injury
• Clinical evidence of severe or uncontrolled alcohol or substance use disorders within three months
• Active withdrawal from alcohol or other substances of abuse
• Implanted metal device in the head that would increase the risk of TMS
• Metal in the head that would increase the risk of TMS
• Current psychosis

Veterans with major depressive disorder (MDD) participating in the VA Clinical TMS Pilot Program. Given the complex nature of the Veteran population, the primary diagnosis of MDD may be comorbid with other disorders, including post-traumatic stress disorder (PTSD).