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Functional as well as structural brain connectivity and epigenetic changes in major depressive disorder associated with remission and persistence of symptoms over a 5 year course

Major Depressive Disorder (MDD) is one of the most prevalent diseases worldwide. Since at present less than one third of patients with MDD achieve remission with an adequate therapeutic trial and the others stay depressed often for a long time, therapy strategies need to be improved and remission needs to be achieved earlier. Experimental animal studies support the notion that dysfunction of neuronal plasticity may contribute to the pathophysiology of MDD, by showing that neuroplastic changes due to stress processes occur during depressive-like states and recover during therapy. To date, these findings have not been translated into a clinical setting.
The proposed research programme is designed to translate findings from experimental studies into clinical practice (1) by determining what dynamic functional and structural brain changes follow the course of the disease (2) by identifying how neuroplastic brain changes are associated with epigenetics, and (3) by using baseline neuroimaging to predict the clinical outcome. Knowledge about how neuroplastic changes and epigenetics are related to them is essential to improve our therapy strategies and to develop new therapy mechanisms. We will apply sophisticated neuroimaging techniques – high resolution hippocampal structural MRI, resting state and emotion-cognitive interplay task related functional MRI and diffusion tensor imaging (DTI) -, neuropsychological testing as well as established epigenetic analysis in glucocorticoid and serotonin transporter genes to the clinical therapeutic setting in 50 patients with MDD and 50 healthy controls. Patients and controls already had been investigated in our depression study and will now be re-investigated 5 years later using the same methods. Thus, we will be able to examine the long-term course of MDD with novel neuroimaging, epigenetics as well clinical and neuropsychological investigations. The project will generate data that can be used in established European networks and can be a basis for further European funding opportunities.