January 25, 2022 (Toronto) - Led by Dr. Tarek Rajji, Chief, Adult Neurodevelopment and Geriatric Psychiatry at the Centre for Addiction and Mental Health (CAMH) and Toronto Dementia Research Alliance (TDRA) Executive Director, a team of Toronto scientists has been awarded a grant by Bell Let’s Talk and Brain Canada to find a long-lasting treatment for depression, a risk factor for dementia.
The approach, currently under development by scientists at CAMH, Sinai Health, and Temerty Faculty of Medicine at the University of Toronto, involves tweaking an existing form of brain stimulation therapy to make it more potent for the treatment of depression.
“It is a very exciting collaboration that combines bench and bedside research in the same project to learn, in an animal model of depression how best to optimize the efficacy of theta-burst stimulation in generating brain plasticity and then apply these learnings in adults with depression using clinical brain stimulation. And, throughout the project, people with lived experience and trainees are directly involved to integrate knowledge translation about bench-to-bedside research throughout all phases of the study,” said Dr. Rajji.
One component on the basic science end of the project is being led by Lunenfeld-Tanenbaum Research Institute (LTRI) Sinai Health and Tanz Centre for Research in Neurodegenerative Diseases researcher Dr. Graham Collingridge, alongside LTRI staff scientist Dr. John Georgiou. Drs. Collingridge and Georgiou are using brain stimulation in a research lab with mice to determine whether changing the rhythm, or spacing, of the pulses to the brain could ultimately deliver long-lasting brain plasticity.
A second component on the bench side also is being led by Temerty Faculty of Medicine researcher, Dr. Evelyn Lambe, preclinical expert in prefrontal cortex, a brain region required for emotional regulation and higher cognition, and will focus on optimizing the above brain stimulation in an animal model for depression. "The goal is to optimize the stimulation of brain cells to create new and lasting connections," according to Evelyn Lambe, one of 4 co-PIs who are leading this project. Dr. Lambe’s team investigates the impact of social isolation on the brain has become increasingly relevant to mental health during the COVID19 pandemic.
The third component of the project will focus on adults with clinical depression. The theta-burst stimulation as optimized in rodents in the first two components will then be adapted to humans using Transcranial Magnetic Stimulation (TMS) and electroencephalograhy (EEG) in Dr. Rajji’s lab. It will then be tested again traditional theta-burst stimulation to examine whether it will lead to better brain plasticity in the frontal lobes of adults with acute depression.
Throughout the above phases, Dr. Sanjeev Sockalingam, a Clinician-Scientist and Vice President of Education at CAMH, leads the knowledge translation component of the project, which includes mental health clinicians, people with lived/living experience and families working with researchers from the start of the grants. “This integrated approach involving clinicians and service users will help us co-create knowledge that gets to people who can use it faster and more effectively”, said Sockalingam.
“We need better and more efficient treatments for depression especially treatments that reduce the cognitive deficits associated with depression and potentially reduce the risk of developing dementia in this high-risk population,” added Dr. Rajji. “Designing a translational project that will bridge within the span of 3 years new discoveries in the basic science labs to advancing clinical therapies for people with depression is a highly promising approach in the quest of these new treatments”.
Another CAMH project funded as part of this initiative is led by Dr. Daniel Blumberger, CAMH Clinician Scientist and Director of the Temerty Centre for Therapeutic Brain Intervention. He and his team will test the efficacy of a novel, 5-day treatment schedule for the approved intermittent theta-burst stimulation (iTBS) protocol as a potential new rapid acting treatment for treatment resistant depression (TRD). The group of investigators have previously demonstrated that iTBS is as effective as standard transcranial magnetic stimulation for TRD, while taking a fraction of the time to administer.
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