Major Depressive Disorder (MDD) is one of the most severe and frequently occurring brain
disorders worldwide. It has been linked to serotonergic dysfunction, sexual dysfunction,
vulnerability to stress and neuro-inflammation. However, at the same time the etiological
understanding is limited. Most antidepressants act on the serotonin (5- HT) system, yet
between 30-50 % of patients with MDD does not respond successfully to 5-HT acting drugs.
Recent experimental models from our group suggest that cerebral 5-HT levels in vivo can be
indexed through molecular brain imaging of the 5-HT 4 receptor (5-HT4R) with a novel Positron
Emission Tomography (PET) ligand (11C-SB207145). Also, our human studies have confirmed that
cerebral synaptic 5-HT is inversely related to 5-HT4R binding and this technique thus can be
used to investigate the role of 5-HT tone in the brain in MDD with differential responses to
standard antidepressant treatment. By using multimodal neuroimaging technology, we aim to
determine the status of the 5-HT system prior to and after either successful or failed
neuropharmacological intervention in a non-randomized longitudinal open clinical trial. 100
untreated patients with moderate to severe MDD will be included. Data collection from various
neurobiological domains (i.e, 5-HT4R PET imaging, Magnetic Resonance Imaging (MRI),
functional MRI (fMRI), electroencephalogram (EEG), psychometrics, neuropsychological tests,
and peripheral biomarkers) will be conducted before, during and after 12 weeks of
antidepressant treatment. The objective is to identify predictors of pharmacological
antidepressant treatment response in depressed individuals before and after 8 weeks of
antidepressant treatment.
Phase:
Phase 1
Details
Lead Sponsor:
Rigshospitalet, Denmark
Collaborators:
Center for Integrated Molecular Brain Imaging Center for Integrated Molecular Brain Imaging, Copenhagen, Denmak Central Visitation, Region Hovedstaden Psychiatric Centre Copenhagen