Grant: CIHR Fellowship

Depression is a severe, debilitating and in many cases, chronic illness, which is often preceded by extreme or prolonged psychological stress. Individuals afflicted by depression show impairment in regulating their emotions and thoughts. Not surprisingly, this impairment is reflected in maladaptive brain activity patterns within key brain areas responsible for the regulation of emotions and thoughts. Yet, neurobiological mechanisms underlying these brain activity patterns still remain largely unknown. Recent studies suggest a contribution of glutamate and one of its specific receptor types, mGluR5, in these processes. Glutamate is the most common messenger in the brain, generally carrying excitatory messages. The mGluR5 have been suggested to play a role in mediating one's response to stress. Furthermore, substances that interfere with function of the mGluR5 have antidepressant-like effects, at least in animal models. However, no study to date has investigated the contribution of the mGluR5 to the changes in brain activity assessed via functional Magnetic Resonance Imaging (fMRI) during rest and in response to psychological stress. Therefore, the goal of the present study is to apply two different neuroimaging technologies (Positron Emission Tomography and fMRI) in order to investigate whether there are differences in levels of the mGluR5 between the groups of healthy, at-risk and depressed subjects, as well as to examine how the levels of mGluR5 may be linked to the brain activity both at rest and in response to a psychological stress task, within and across each study group. Investigating the contribution of glutamate receptors to maladaptive changes in brain activity can help further our understanding of the neurobiology underlying this complex illness and therefore advance the development of more specific prevention and treatment approaches.