We are thrilled to announce that Prof. Vibe G. Frøkjær has been awarded a Lundbeck Foundation Ascending Investigator grant worth 5.911.743 DKK. This prestigious grant is for the proposed 4-year project 'Clinical translation of serotonin 4 receptor agonism: an antidepressant and pro-cognitive target' which is summarized below.
Summary of project:
Major Depressive Disorder (MDD) is an enormous public health problem that predominantly affects women and we urgently need faster acting and more efficient treatment options. A disabling and often underrecognized symptom in patients with MDD is the presence of cognitive disturbances, including impaired memory and learning capacity. Traditional antidepressant treatments such as SSRIs offer only limited improvements in cognitive function. Thus, treatments that promote cognitive function would be paramount for full recovery in patients with MDD and improve long-term outcomes.
The serotonin 4 receptor (5-HT4R) in the brain is a promising novel pro- cognitive and antidepressant target. It is markedly reduced in unmedicated patients with MDD and is linked to memory symptoms as well as anhedonia, i.e., diminished access to pleasure, another core feature of MDD in women.
We here propose a randomized, placebo-controlled, double-blinded clinical trial to determine if pharmacological stimulation of the serotonin 4 receptor as augmentation to standard SSRI treatment relative to SSRI alone has pro-cognitive and antidepressant effects. We will repurpose prucalopride, a drug commonly used to treat chronic constipation, which target the 5-HT4R. Before initiating the trial, we will determine the optimal dose by a so-called occupancy study possible at our center since we have implemented scanner methods to map 5-HT4R in the brain. By leveraging frontier functional imaging methodology, we will also illuminate plausible, distinct antidepressant treatment mechanisms, i.e. treatment induced brain network re-organizations. The work will run in a strong international collaboration with leading experts in applied neuropsychopharmacology at Department of Psychiatry, Oxford University, UK.
This project holds grand promise to improve mental health in women, and in next steps will inform broader translation to promote cognitive brain health.