The proposed project will investigate the neurobiological mechanisms of accelerated intermittent Theta Burst Stimulation (iTBS) in major depressive disorder (MDD) using an advanced multimodal imaging approach. This single-arm, within-subject study will deliver one week of accelerated iTBS and use pre-/post-treatment PET/MRI to quantify changes in synaptic density, functional connectivity, and microstructural integrity. We will combine \[¹⁸F\]SynVesT-1 PET with functional, neurochemical and anatomical MRI, such as resting-state fMRI, magnetic resonance spectroscopy (MRS) and neurite orientation dispersion and density imaging (NODDI), to capture treatment-related plasticity. This integrated design will link molecular and network-level mechanisms to clinical improvement, providing an unprecedented mechanistic map of how accelerated iTBS restores brain function in depression.
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.
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
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.
Significant unstable medical or neurologic illness confirmed by medical history (e.g. uncontrolled diabetes, or renal dysfunction).
The Royal Ottawa Mental Health Centre
Lead sponsor