Grant: Project Grant

Over the last several decades, a non-invasive brain stimulation treatment called repetitive Transcranial Magnetic Stimulation (rTMS) has emerged as a treatment for Major Depressive Disorder (MDD). rTMS targets brain regions implicated in MDD through a process called synaptic plasticity. Unfortunately, not everyone benefits from rTMS, and one of the potential reasons for this is that synaptic plasticity is impaired in MDD, something supported by several lines of evidence from cognitive testing to cellular changes in the brain. One possibility is that by pairing rTMS with a drug that enhances synaptic plasticity can improve outcomes. One of the key regulators of synaptic plasticity is the N-methyl-D-aspartate receptor (NMDAr), and our previous work has shown that we can stabilize synaptic plasticity with a medication that targets this receptor called D-cycloserine. We hypothesize that D-cycloserine will enhance the effects of rTMS, which in turn will enhance its antidepressant effects, but also the cognitive and cellular changes seen in MDD. To achieve this, we will examine how much individuals with MDD improve when rTMS is paired with D-cycloserine compared to rTMS paired with a placebo pill. We will also use cognitive testing to determine whether the combination of D-Cycloserine and rTMS improves brain functions that are impaired in MDD, and we will use novel brain imaging tools to study microstructural markers of brain remodelling to understand how the combination is facilitating change in the brain. This study is important, because if outcomes can be enhanced with this strategy it provides a low-cost and scalable means of enhancing Canadians' mental health outcomes with existing infrastructure.