Grant: Project Grant

Treatment resistant clinical depression is much more likely when comorbid illness is present. We think that when comorbid illnesses are present, brain changes that are resistant to antidepressant treatment occur like brain inflammation and loss of connections between the nerves. We previously discovered inflammation in the brain in clinical depression and a common comorbid illness called obsessive compulsive disorder. In our pilot data of clinical depression with certain comorbid conditions we see that brain inflammation is exceptionally elevated. We propose to study whether brain inflammation is particularly increased in clinical depression with certain comorbid illnesses namely, obsessive compulsive disorder, anorexia nervosa and generalized anxiety disorder. When brain inflammation is present some brain cells that are part of the inflammation can remove synapses, the connections between brain cells. We also propose to determine whether there are less synapses when there is greater brain inflammation. It is believed that loss of synapses occurs in clinical depression but the data supporting this in humans is one small sample so we also propose to study synaptic density in a much larger sample of depressed and healthy subjects. To measure brain inflammation and synaptic density we will use state of the art brain scanning methods. Key impacts are: 1)If inflammation is greater in clinical depression with these comorbidities, then new treatments targeting brain inflammation should be tested in such cases. 2) If all these illnesses have the same kind of inflammation, they should be categorized as being similar illnesses. 3)If we identify loss of synapses in clinical depression with brain imaging we can use this method to discover treatments targeting loss of synapses and optimize their administration. 4)If loss of synapses occurs when inflammation is present we could make new cures to guide inflammatory processes away from removing synapses.