Title: A novel marker of brain serotonin as predictor of respons to antidepressant therapy

PhD-student: Kristin Köhler-Forsberg, NRU and Psychiatric Centre Copenhagen


Depression is a tremendously burdensome disease, both from an economic and individual perspective. Despite several treatments, many patients do not respond sufficiently to available antidepressant regimens. A major problem is the lack of  predictability of whether a given patient will  benefit from a specific antidepressant. The  conventional medical treatments are predominantly based on  intervention of the brain serotonergic system and currently there are no markers able to predict treatment response. We have developed a novel biomarker that binds to a serotonin receptor (5-­HT4R) in the brain. Recent studies, in particular with positron emission tomography (PET) scanning in humans, suggest that the extent of this binding index the serotonergic tone in the brain.

We therefore wish to determine if a PET scan, with the use of this marker, can predict treatment response  to a specific serotonergic drug (Escitalopram) among patients with major depressive disorder (MDD). We will conduct a clinical study  including 100 patients and conduct PET brain imaging before and after Escitalopram treatment.

The primary aim is to determine the predictive value of 5-­HT4R binding for the outcome of a pharmacological intervention in MDD and to determine if treatment induced changes in 5-­HT4R binding differentiates responders from non-­responders. Ideally, the prospective is that PET 5-­‐HT4R binding, as an index of serotonin dysfunction, predicts treatment response and thus may help to pave the way for more individualized, targeted and optimized treatment strategies.

The secondary aim is to identify subgroups within the spectrum of depressed patients by applying imaging techniques, thereby possibly further explaining the variable response.