Grant: Project Grant

It is estimated that 30% of individuals with Major Depressive Disorder (MDD) do not significantly improve with antidepressant medication, accounting for over 1 million Canadians in their lifetime. Treatment resistant depression (TRD), defined as a failure of at least two antidepressant trials for the current episode, results in almost double the health-associated costs and a greater likelihood of occupational disability, causing significant economic and personal burden. Importantly, there are few treatment strategies to target TRD and we do not have a comprehensive understanding of what processes in the brain cause it. Preliminary evidence from our group suggests there is an impairment in the dopamine system that plays an important role in processing rewarding stimuli. Deficits in this system are associated with loss of pleasure, one of the core symptoms of depression that is more prevalent in those with TRD. How the dopamine system functions in TRD compared to non-resistant patients and the full extent of the impairment is unclear. Consequently, more comprehensive evaluation of the dopamine system is necessary to determine if it is a relevant avenue for the development of new therapeutics. The goal of this study is to characterize the dopamine system in the brain within patients with TRD, non-resistant MDD and healthy controls. Three groups of participants aged 25-55 will be recruited: 15 unmedicated MDD, 15 unmedicated TRD, and 15 healthy controls. The TRD and MDD groups will have depression of moderate severity with no presence of bipolarity, psychosis or substance abuse. Healthy controls will have no lifetime psychiatric history. Imaging of the dopamine system will be done using two positron emission tomography (PET) scans to determine impairment across the whole brain. Results of this study will represent the first comprehensive assessment of dopamine in the brain among resistant and non-resistant MDD patients.