We did not receive grant funding for this study.

The purpose of this study is to utilize the radioactive positron emission tomography (PET) tracer [11C]UCB-J to investigate the effect of repetitive transcranial magnetic stimulation (rTMS) on synaptic plasticity. UCB-J has been validated as a marker for synaptic density. We will use this tracer to examine if rTMS leads to changes in synaptic plasticity, specifically changes in synaptic density, in individuals receiving rTMS for MDD. If rTMS is proven effective for increasing synaptic plasticity, there is a significant potential of a new applicable treatment for a variety of diseases that affect brain physiology.

The objective of this project is to discover the neural mechanisms by which Major Depressive Disorder (MDD) is treated, so that we may gain insights into its pathophysiology, as well as to develop new biomarkers. We will utilize the PET tracer [11C]UCB-J, the first in human tracer of neural synapses, to test the hypothesis that the successful treatment of MDD with repetitive Transcranial Magnetic Stimulation (rTMS) is associated with increased synaptic density. We will use this tracer to measure synaptic density before and after rTMS treatment and compare change in synaptic density between subjects who respond to the rTMS treatment and those who do not respond to treatment.

The finding of a marked increase in synaptic density in participants who respond to rTMS treatment would point to the possibility of developing new treatments with the potential to modify disease through mitigating, preventing or remediating synaptic loss.

Inclusion Criteria:

• 18-70 years in age
• U.S. Veteran
• Diagnosis of MDD
• On a stable medication regimen for at least two weeks prior to testing
• Stable social environment and housing to enable regular attendance at clinic visits
• Ability to undergo cognitive testing, clinical assessments, and PET/MR scans
• Stable medical health
• Will undergo rTMS treatment for MDD at the VA Palo Alto
• Able to complete a PET-MR scan without the use of sedation

Exclusion Criteria:

• Active substance use within three months of testing
• IQ < 70
• Major medical neurological illness or significant head trauma
• Pregnancy or breastfeeding
• Contraindication to MR scanning, including magnetic-resonance incompatible metal or hardware including pacemakers, cochlear implants, and bullets near a critical organ
• Weight > 350 lbs or a large body habitus that MR scanner cannot accommodate
• History of or current claustrophobia
• Inability to comply with basic study requirements such as following directions and punctuality
• Acute or unstable chronic medical illness that would affect participation or compliance with study procedures, e.g. unstable angina
• Unstable psychiatric symptoms that precludes consistent participation in the study, e.g. active current suicidal intent or plan, severe psychosis
• Inability to undergo PET/MR scan, e.g. claustrophobia, presence of ferromagnetic objects in subject's body

No current plan to share data