Grant: CIHR Fellowship

Major depressive disorder (MDD) represents the leading cause of disability, affecting over 300 million people worldwide. Largely characterized by behavioural symptoms, there is a need to identify biological changes, or 'biomarkers', associated with MDD for effective diagnosis and treatment, as 30-50% of patients with MDD do not respond to current antidepressant therapies. Recent findings suggest that MDD or chronic stress may be associated with inflammation - a response of the immune system to danger - and that this inflammation triggers depressive behaviour. However, the link between inflammation and depression has not been widely characterized. Moreover, it is not known how stress initiates inflammation or how this inflammation acts on the brain to influence mood and behaviour. The goal of this project is to generate a comprehensive profile of inflammation during MDD. Using blood from human patients with MDD or a mouse model of depression, we will analyze cells of the immune system to determine if they more readily migrate towards, or are more prone to attacking, the brain. To further expand this profile, we will measure levels of 'cytokines', inflammatory messengers produced by immune cells, in these blood samples. Once we have identified potential inflammatory mediators of depression, we genetically deplete these candidate factors in mice to test their role in susceptibility to stress-induced depression. To elucidate the mechanisms of how inflammation alters behaviour, we will focus on the effects on brain cells that regulate mood and motivation, along with cells that comprise the blood-brain barrier, which normally protects the brain from danger. Understanding an inflammatory basis of MDD will be critical in developing diagnostic criteria and novel antidepressant drugs.