PAVING THE ROAD FOR PRECISION MEDICINE: THE ROLE OF STRESS MONITORING AND INFLAMMATION IN DEPRESSION

Major Depressive Disorder (MDD), in many patients, takes the form of a chronic, relapsing-remitting disorder. During past decades, it has become clear that biological changes may underlie MDD (1) . These changes do not only suggest a biological base of mood disorders, but may also be used as tool to predict response and relapse and can hence provide valuable information as to the selection of adequate treatment for patients with MDD. One of the established biological changes in MDD may arise from a disturbed immune system. The interaction between the immune system, and other established changes such as HPA axis alterations, and eventually mood, this pathway is a good candidate for a possible biomarker in MDD (2). During the Mood inflame project, a European cooperation aiming to identify biomarkers of mood disorders, data about the immune cell profile in patients with MDD have been collected. Part one of this doctoral plan is to analyse this data in MDD patients of the Mood inflame project with focus on specific clinical factors that have been linked to inflammation, such as suicide risk and childhood adversity. In a second project, we will explore whether the established differences of autonomic nervous system markers such as heart rate (HR) and its variability (HRV) can be used for state monitoring in depression. Given the important role of stress on depression pathogenesis and HR/HRV we will first adress important questions as to alterations during different states of stress. This includes conducting a systematic review on HR/HRV during stress in depressed patients, and an experimental study, where for the first time, we will re-expose patients with depression to exactly the same stress task, to test their capacity of adaptation to stress, and possibly explain the blunting of HR/HRV. Lastly, we will conduct a clinical trial using ketamine to assess whether rapid changes in mood can be linked to autonomic and/or immune changes. The non-competitive N-methyl-aspartate (NMDA) receptor antagonist ketamine has shown potential for treating MDD by its rapid onset of antidepressant effects (3). Several recently completed clinical trials show good efficacy in reduction of depressive symptoms (4,5) and suicidal ideation (6), albeit only short lasting. We here use ketamine as paradigm to assess the correlation between mood and HRV/immune parameters.status: publishe